StudyFinder
Search Results Within Category "Neurology"
62 Study Matches
Setting Families on a Positive Path to Recovery After Pediatric TBI: Road-to-Recovery
Shari Wade - Shari.Wade@cchmc.org
ALL
18 years and over
NA
NCT05622461
Inclusion Criteria:
Caregivers will be eligible if they are over 18 years of age, and if their child meets all of the following criteria:
* Ages 3 months to 18 years at time of discharge from hospital
* Sustained a complicated mild to severe TBI as defined by a Glasgow Coma Scale (GCS) of 13-15 with imagining abnormalities or GCS 3-12 with or without imaging abnormalities
* Admitted overnight to the hospital
* 0-3 months post-discharge
Exclusion Criteria:
The caregiver will be excluded from participation if any of the following occur:
* Child did not survive the injury
* Child sustained a non-blunt head trauma (e.g. gunshot wound)
* Child does not reside with parent/caregiver for study duration
* English is not primary language spoken in the home BEHAVIORAL: Road-to-recovery
Traumatic Brain Injury, Head Injury, Head Injuries, Closed, Brain Hemorrhage, Traumatic, Brain Edema, Intracranial Edema
A Phase I/II Study of Trametinib and Azacitidine for Patients With Newly Diagnosed Juvenile Myelomonocytic Leukemia
cancer@cchmc.org
ALL
1 month to 21 years old
PHASE1
NCT05849662
Inclusion Criteria:
Age
• Patients must be ≥ 1 month and ≤21 years of age at enrollment.
Diagnosis • Patients must meet the 2022 International Consensus Classification criteria for JMML. The diagnosis is made based on the following criteria:.
Clinical and hematologic features (the first 2 features are present in most cases; the last 2 are required):
* Peripheral blood monocyte count ≥ 1 × 109/L\*
* Splenomegaly†
* Blast percentage in PB and BM \< 20%
* Absence of BCR::ABL1
* This monocyte threshold is not reached in approximately 7% of cases. †Splenomegaly is absent in 3% of cases at presentation.
II. Genetic studies (1 finding required):
* Somatic mutation in PTPN11‡ or KRAS‡ or NRAS‡ or RRAS or RRAS2‡
* Clinical diagnosis of neurofibromatosis type 1 or germline NF1 mutation and loss of heterozygosity of NF1 or somatic biallelic loss of NF1
* Germline CBL mutation and loss of heterozygosity of CBL, or somatic mutation(s) in CBL§
* Germline mutations (indicating Noonan syndrome) need to be excluded. §Occasional cases with heterozygous splice site mutations.
Performance Level
* Karnofsky \> 50% for patients ≥ 16 years of age
* Lansky \> 50% for patients \< 16 years of age.
Prior Therapy
* No prior leukemia directed therapy is permitted with the exception of:
• Cytoreduction with hydroxyurea can be initiated and continued for up to 24 hours prior to the start of trametinib.
• Cytoreduction with 6-mercaptopurine (6-MP) 6-MP can be initiated and continued for up to 72 hours prior to the start of trametinib.
• Intrathecal (IT) cytarabine, IT methotrexate or triple IT therapy (cytarabine, methotrexate and hydrocortisone) within 7 days of enrollment as part of a diagnostic evaluation. No prior hematopoietic stem cell transplant is permitted. Adequate Renal Function Defined as: * Patient must have a calculated creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73m2 OR a normal serum creatinine based on age/gender in the chart below: Maximum Serum Creatinine (mg/dL): * 1 month to \< 6 months old - Male: 0.4, Female 0.4 * 6 months to \<1 year old - Male 0.5, Female 0.5 * 1 to \< 2 years old - Male: 0.6, Female: 0.6 * 2 to \< 6 years old - Male:0.8, Female: 0.8 * 6 to \< 10 years old - Male: 1, Female: 1 * 10 to \< 13 years old - Male: 1.2, Female: 1.2 * 13 to \< 16 years old - Male: 1.5, Female: 1.4 * ≥ 16 years old - Male: 1.7, Female: 1.4 The threshold creatinine values in this Table were derived from the Schwartz formula for estimating GFR (Schwartz et al. J. Peds, 106:522, 1985) utilizing child length and stature data published by the CDC. Adequate Liver Function Defined as: * Direct bilirubin \< 1.5 x upper limit of normal (ULN) for age or normal, AND alanine transaminase (ALT) \< 5 x ULN for age. * The hepatic requirements are waived for patients with known or suspected liver involvement by leukemia and will not be evaluable for hepatotoxicity. This must be reviewed and approved by the study chair or vice chair. Adequate Cardiac Function Defined as: * Ejection fraction of \> or = to 50% by echocardiogram, OR * Ejection fraction of \> or = to 50% by radionuclide angiogram (MUGA). Reproductive Function * Female patients of childbearing potential must have a negative urine or serum pregnancy test confirmed within 2 weeks prior to enrollment. * Female patients with infants must agree not to breastfeed their infants while on this study. * Male and female patients of child-bearing potential must agree to use an effective method of contraception approved by the investigator during the study and for a minimum of 6 months after study treatment.
Exclusion Criteria:
* Patients cannot have a known allergy to any of the drugs used in the study.
* Patients cannot have a systemic fungal, bacterial, viral, or other infection that is exhibiting ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment. The patient needs to be off pressors and have negative blood cultures for 48 hours.
* Patients cannot have a plan to administer non-protocol chemotherapy, radiation therapy, or immunotherapy during the study period.
* Patients cannot have significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance with the protocol treatment or procedures, interfere with consent, study participation, follow up, or interpretation of study results.
* Patients cannot have a clinical or molecular diagnosis of Noonan syndrome. Note: patients with either neurofibromatosis type 1 or Casitas B-lineage lymphoma (CBL) syndrome (also known as Noonan-like syndrome), are eligible to enroll. Patients with Down syndrome are excluded from the study.
* Patient cannot have had prior use of hematopoietic growth factors, biologics (anti-neoplastic agent), or XRT.
* Patients cannot be taking any medications for treatment of left ventricular systolic dysfunction.
* Patients cannot have a history of or current evidence of retinal vein occlusion (RVO) or central serous retinopathy (CSR).
* Patients cannot have had prior use of any MEK inhibitor. DRUG: Trametinib, DRUG: Azacitidine, DRUG: Fludarabine, DRUG: Cytarabine
Leukemia, Juvenile Myelomonocytic, JMML, JCML, Neurofibromatosis 1, CBL Syndrome
Sinus Disease in Young Children With Cystic Fibrosis
Megan Schmitt - megan.schmitt@cchmc.org
ALL
2 years to 8 years old
NCT06191640
Inclusion Criteria:
HEMT Group:
* Children with documentation of a CF diagnosis
* Age 2-8 years old at first study visit
* CFTR mutation consistent with FDA labeled indication of highly effective modulator therapy (ivacaftor or elexacaftor/tezacaftor/ivacaftor)
* Clinician intent to prescribe ivacaftor or ETI so that enrollment is before start of HEMT
Non-HEMT/Control Group:
* Children with documentation of a CF diagnosis
* Age 2-8 years at first study visit
* Ineligible for highly effective modulator therapy (ivacaftor or elexacaftor/tezacaftor/ivacaftor) based on CFTR mutation or clinical decision not to initiate HEMT if eligible
Exclusion Criteria:
For Both Groups:
* Use of an investigational drug within 28 days prior to the first study visit
* Use of ivacaftor or elexacaftor/tezacaftor/ivacaftor within the 180 days prior to and including the first study visit
* Use of chronic oral corticosteroids within the 28 days prior to and including the first study visit.
* Sinus surgery within 180 days prior to the first study visit DRUG: Ivacaftor or elexacaftor/tezacaftor/ivacaftor
Cystic Fibrosis in Children, Cystic Fibrosis, Chronic Rhinosinusitis (Diagnosis), Olfactory Disorder, Olfactory Impairment
Cystic Fibrosis, Chronic Rhinosinusitis, Olfactory Dysfunction
Safety and Efficacy Study of Intracystic TARA-002 for the Treatment of Lymphatic Malformations in Participants 6 Months to Less Than 18 Years of Age (STARBORN-1)
Kimberly Whittaker - kimberly.whittaker@cchmc.org
ALL
6 months to 18 years old
PHASE2
NCT05871970
Inclusion Criteria:
* Male or female participants 6 months to less than 18 years of age at the time of informed consent/assent form was signed
* Participants whose parent/LAR(s) have voluntarily given written consent and participants who provided assent (if applicable) after the study has been explained to them
* Participants with macrocystic LM or mixed cystic LM (≥ 50% macrocystic disease measured by volume) of the Head/Neck/Mediastinum according to the ISSVA 2018 criteria (ISSVA 2018) measured via LM imaging at Screening to confirm, upon central review, the diagnosis of macrocystic or mixed cystic LM
* Participants who may have had surgical or sclerotherapy treatment for their LM, but not within six months of the consent/assent form being signed
Exclusion Criteria:
* Penicillin allergy
* Vascular tumors or combined vascular malformations
* Microcystic LM or mixed cystic LM with predominant microcystic features
* LMs of the orbit (orbital LM) as target cyst
For more information on eligibility criteria, please contact the sponsor. BIOLOGICAL: TARA-002
Lymphatic Malformation
Macrocystic lymphatic malformations, Mixed-cystic lymphatic malformations
MEKTOVI® for the Treatment of Pediatric Adamantinomatous Craniopharyngioma
- cancer@cchmc.org
ALL
1 year to 39 years old
PHASE2
NCT05286788
Inclusion Criteria:
• Age: Patients must be ≥ 12 months and ≤ 39 years of age at the time of study enrollment.
• Diagnosis: Patients with histologically-confirmed adamantinomatous craniopharyngioma (ACP) Histologic confirmation of ACP may be made on solid tumor or, if no solid tumor can be safely obtained, cyst fluid with classic ACP characteristics of thick, cholesterol-rich, greenish-brown liquid in the context of imaging features consistent with craniopharyngioma, including lobulated, cystic/solid mass with calcifications that originates in the sellar/suprasellar region.
• Disease Status: Patients must have measurable disease. * Stratum 1: Patients with progressive or recurrent ACP who demonstrate cystic and/or solid recurrence or progression at least 6 months post completion of radiation therapy * Stratum 2 (NOT CURRENTLY ENROLLING): Patients with measurable ACP who have undergone surgery but have NOT previously undergone irradiation (but may have received prior systemic or intracystic therapy). Progressive disease is allowed but not required.
• Performance Level: Karnofsky ≥ 50% for patients \> 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of age (See Appendix I). Note: Neurologic deficits in patients with CNS tumors must have been stable for at least 7 days prior to study enrollment. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
• Prior Therapy: Patients must have recovered or stabilized from the acute toxic effects of prior treatments * Biologic (anti-neoplastic agent): At least 7 days must have elapsed after the last (systemic or intracystic) dose of a biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair * Immunotherapy: At least 42 days after the completion of any type of systemic immunotherapy, e.g. tumor vaccines. * Monoclonal antibodies: At least 21 days after the last dose of a monoclonal antibody. * Radiation therapy: Patients must have had their last (conventional or hypofractionated) fraction of: a) Focal irradiation \> 6 months prior to enrollment and b) No prior craniospinal irradiation is permitted. * Corticosteroids: Patients receiving dexamethasone must be on a stable or decreasing dose for at least 1 week prior to enrollment * Myelosuppressive systemic therapy: At least 21 days must have elapsed after the last systemic myelosuppressive therapy. * Surgery: At least 6 weeks must have elapsed since major or intermediate surgery. Major surgery includes major craniotomy for tumor resection of cyst fenestration, organ resection, and exploratory laparotomy. Intermediate procedures include ventriculoperitoneal shunt placement, stereotactic brain biopsy, and intraventricular catheter placement. Minor procedures that are not excluded include skin biopsy/incision and drainage, bone marrow aspirate, and central venous catheter placement, ommaya aspirations, lumbar punctures, and nasal endoscopy to remove packing.
• Organ Function Requirements Adequate Bone Marrow Function Defined as: * Peripheral absolute neutrophil count (ANC) ≥1000/mm3 * Platelet count ≥100,000/mm3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) * Hemoglobin \>8 g/dL (may be transfused) Adequate Renal Function Defined as: * Creatinine clearance or radioisotope GFR \> 70ml/min/1.73 m2 or * A serum creatinine based on (Schwartz et al. J. Peds, 106:522, 1985) age/gender as follows:
• to \< 2 years: maximum serum creatinine 0.6 mg/dL for males and females. 2 to \< 6 years: maximum serum creatinine 0.8 mg/dL for males and females. 6 to \< 10 years: maximum serum creatinine 1.0 mg/dL for males and females. 10 to \< 13 years: maximum serum creatinine 1.2 mg/dL for males and females. 13 to \< 16 years: maximum serum creatinine 1.5 mg/dL for males and 1.4 mg/dL for females. ≥ 16 years: maximum serum creatinine 1.7 mg/dL for males and 1.4 mg/dL for females. Adequate Liver Function Defined as: * Total bilirubin ≤ 1.5 × institutional upper limit of normal * AST (SGOT) ≤ 2.5 × institutional upper limit of normal * ALT (SGPT) ≤ 2.5 × institutional upper limit of normal Adequate Cardiac Function Defined as: * Left Ventricular Ejection Fraction greater than the institutional lower limit of normal by echocardiogram * QTc ≤ 480 msec (by Bazett formula) Adequate Neurologic Function Defined as: * Patients with neurological deficits should have deficits that are stable for a minimum of 1 week prior to enrollment. * Patients with current seizure disorders may be enrolled if seizures are well-controlled on antiepileptic therapies.
• Informed Consent: All patients and/or their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines
Exclusion Criteria:
• Pregnancy or Breast-Feeding: Pregnant or breast-feeding women will not be entered on this study due to unknown risks of fetal and teratogenic adverse events as seen in animal/human studies. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method for at least 90 days after discontinuation of drug for females and at least 60 days for males. For females of childbearing potential, agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods (bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices; hormonal contraceptive methods must be supplemented by a barrier method) and agreement to refrain from donating eggs are required. For males of reproductive potential, agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm.
• Gastrointestinal Disease: * Patients with a history of serious gastrointestinal disease, including inflammatory bowel disease or gastrointestinal perforation * Patients who are unable to absorb enteral medications * Administration via NG/NJ/G-tube is allowed
• Concomitant Medications * Corticosteroids: Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible. * Investigational Drugs: Patients who are currently receiving another investigational drug are not eligible. * Anti-cancer Agents: Patients who are currently receiving other anti-cancer agents are not eligible.
• Study Specific: * Patients who have an uncontrolled infection are not eligible. * Patients who have received any live or attenuated vaccinations within three months prior to start of therapy are not eligible. * Any significant concurrent medical or surgical condition that would jeopardize the patient's safety or ability to complete the study, including, but not limited to, disease of the nervous, renal, hepatic, cardiac (such as symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia), pulmonary, or endocrine system * Patients who have a history of Human Immunodeficiency Virus, Hepatitis B Virus, Hepatitis C Virus or Tuberculosis infection are not eligible. * Patients who have received a prior solid organ transplantation are not eligible. * Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible. * Patients who have a history of alcohol, drug, or chemical abuse within 6 months of screening. * Patients who have had surgery within the last 6 weeks or who have concerns for poor postsurgical wound healing. * Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to tocilizumab and its excipients are not eligible.
DRUG: Binimetinib Oral Tablet [Mektovi]
Adamantinous Craniopharyngioma, Recurrent Adamantinomatous Craniopharyngioma
Study of Ribociclib and Everolimus in HGG and DIPG or Ribociclib and Temozolomide in DHG, H3G34-mutant
- cancer@cchmc.org
ALL
12 months to 39 years old
PHASE2
NCT05843253
TarGeT-A study strata definitions Part1: Initial Feasibility Study for the combination of ribociclib PfOS formulation with everolimus: Enrollment on this cohort will be limited to patients aged \<21 years with primary intracranial localized HGG and DIPG
Part 2
* Stratum A: Patients with localized, intracranial, non-pontine, and non-thalamic HGG (who do not meet criteria for strata C-D)
* Stratum B: Patients with DIPG
* Stratum C: Patients with primary thalamic, spinal cord, and/or secondary/radiation-related HGG.
* Stratum D: Patients with metastatic/disseminated HGG, multifocal HGG, and/or gliomatosis cerebri who received CSI.
Stratum E
* Stratum E: Patients with localized DHG, H3G34-mutant.
• Inclusion criteria already met to enroll on TarGeT-SCR (central molecular and histopathologic screening) based on:
• 1) Age: patients must be ≥12 months and ≤39 years of age at the time of enrollment on TarGeT-SCR. For the Part 1 Initial Feasibility Cohort (receiving ribociclib and everolimus) only: patients must be \<21 years of age at the time of enrollment on this protocol.
• 2) Diagnosis: patients with newly-diagnosed HGG, including DIPG are eligible. All patients must have histologic confirmation tumor tissue from diagnostic biopsy or resection, without exceptions. The diagnosis of HGG, including DIPG, must have been confirmed through TarGeT-SCR: * For the diagnosis of DIPG, patients must have a tumor with pontine epicenter and diffuse involvement of at least 2/3 of the pons, with histopathology, consistent with diffuse WHO grade 2-4 glioma * All other HGGs must be WHO grade 3 or 4.
• 3) Disease status: There are no disease status requirements for enrollment * Patients without measurable disease are eligible. * Patients with metastatic or multifocal disease or gliomatosis cerebri who received upfront CSI are eligible * Patients with a primary spinal HGG are eligible * Patients with secondary, radiation-related HGG are eligible.
• Inclusion criteria for assignment to TarGeT-A, for all strata:
• 1) Presence of at least one relevant actionable somatic alteration, detailed here: * Pathogenic alterations presumed to cause activation of cell cycle: * Amplification of CDK4 or CDK6 * Deletion of CDKN2A, CDKN2B, or CDKN2C * Amplification of CCND1 or CCND2 * Pathogenic alterations presumed to cause activation of the PI3K/mTOR pathway: * Deletion or mutation of PTEN * Mutation or amplification of PIK3CA * Mutation of PIK3R1 * Deletion or mutation of TSC1 or TSC2 * Patients with evidence of homozygous (biallelic) RB1 loss by sequencing are excluded from TarGeT-A * Patients whose tumors harbor other alterations suspected to activate the cell cycle and/or PI3K/mTOR pathway could potentially also be eligible, but only following consensus recommendation by the international multidisciplinary molecular screening committee. * For Stratum E: H3G34 (R/V) mutation
• 2) Performance Level: Karnofsky ≥ 50% for patients \> 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of ag. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
• 3) Prior Therapy for HGG: * Surgery, RT, dexamethasone are permissible. Temozolomide administered concurrently with RT is permissible. Avastin/bevacizumab use is permitted given the last dose was administered \> 21 days prior to enrollment. No other prior anticancer therapy for HGG will be allowed. * Patients must have received photon or proton RT. * Patients must have started RT \< 42 calendar days from initial diagnosis defined as the date of diagnostic biopsy or resection. If a patient underwent 2 upfront surgeries (e.g., biopsy then resection or debulking), this is the date of the second surgery. * RT delivered via photon or proton beam, must have been administered at a standard dose including (54 Gy in 30 fractions for DIPG, 54-59.4 Gy in 30-33 fractions), 45 Gy-54 Gy for primary spinal disease, and/or 36 Gy-39.6 Gy craniospinal for patients with spinal or leptomeningeal metastatic disease with supplemental boost to 45-54 Gy for metastasis within the thecal sac and 54 Gy-60 Gy for intracranial metastasis. Any variances in the radiotherapy dose within 10% of the standard doses outlined above will be discussed with the Sponsor-Investigator to confirm eligibility prior to study enrollment. * Patients must enroll and start treatment No later than 35 calendar days post-completion of RT. The earliest patients can begin protocol treatment is 28 calendar days post-completion of RT.
• 4) Organ Function Requirements
• 4.1) Adequate Bone Marrow Function Defined as: * Peripheral absolute neutrophil count (ANC) ≥ 1000/mm3 * Platelet count ≥ 100,000/mm3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) * Hemoglobin \>8 g/dL (may be transfused)
• 4.2) Adequate Renal Function Defined as: * Creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73 m2 OR * Maximum serum creatinine based on (Schwartz et al. J. Peds, 106:522, 1985) age/gender as follows: 1 to \< 2 years=0.6 mg/dL for males and females; 2 to \< 6 years=0.8 mg/dL for males and females; 6 to \< 10 years= 1.0 mg/dL for males and females; 10 to \< 13 years=1.2 mg/dL for males and females. 13 to \< 16 years=1.5 mg/dL for males and 1.4 mg/dL for females.
• 4.3) Adequate Liver Function Defined as: * Total bilirubin must be ≤ 1.5 times institutional upper limit of normal for age * AST(SGOT)/ALT(SGPT) ≤ 3 times institutional upper limit of normal * Serum albumin ≥ 2g/dL
• 4.4) Adequate Cardiac Function Defined as: * Ejection fraction of ≥ 50% by echocardiogram * QTc ≤ 450 msec (by Bazett formula)
• 4.5) Adequate Neurologic Function Defined as: Patients with seizure disorder may be enrolled if well-controlled on anticonvulsants that are not strong inducers or inhibitors of CYP3A4/5.
• 4.6) Adequate Pulmonary Function Defined as: No evidence of dyspnea at rest, and a pulse oximetry \>94% on room air if there is clinical indication for determination.
• 5) Ability to take medications by mouth: For ribociclib and everolimus strata, patients must be able to take study medications by mouth as administration via NG/NJ/G tube is not allowed.
• 6) Informed Consent: All patients and/or their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines
• 7) Contraception: Male and female patients of childbearing potential must be willing to use a highly effective contraception method. Exclusion Criteria
• Pregnant or Breast-Feeding Pregnant or breast-feeding women will not be entered on this study due to known potential risks of fetal and teratogenic adverse events as seen in animal/human studies. Pregnancy tests must be obtained in girls who are post-menarchal. Patients of childbearing or child fathering potential must agree to use at least one highly effective method of contraception while being treated on this study and for 3 months after completing therapy. A woman is considered of childbearing potential if she is fertile, following menarche and until becoming post-menopausal unless permanently sterile. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. A man is considered fertile after puberty unless permanently sterile by bilateral orchidectomy. Male participants should refrain from sperm donation throughout the duration of treatment and for 3 months after completion of therapy A highly effective contraception method is defined as one that results in a low failure rate (\<1% per year) when used consistently and correctly. The following are considered highly effective contraception methods: * Combined estrogen and progesterone containing hormonal contraception associated with inhibition of ovulation. * Progesterone-only hormonal contraception associated with inhibition of ovulation. * Intra Uterine Device (IUD) * Intra Uterine hormone releasing system * Bilateral tubal occlusion * Vasectomized partner * Sexual abstinence (avoiding having heterosexual intercourse) The following contraceptive measures are NOT considered effective * Progesterone-only hormonal contraception (birth control pill) that that does NOT stop ovulation * Male or female condom with or without spermicide * Cap, diaphragm or sponge with spermicide
• Concomitant Medications * Patients receiving corticosteroids are eligible. The use of corticosteroids must be reported. * Patients who are currently receiving another investigational drug are not eligible. * Patients who are currently receiving other anti-cancer agents are not eligible, with the exception of temozolomide given concurrently with RT only. * Patients who are receiving enzyme inducing anticonvulsants that are strong inducers or inhibitors of CYP3A4/5 are not eligible. * Patients who are receiving strong inducers or inhibitors of CYP3A4/5 are not eligible and should be avoided from 14 days prior to enrollment to the end of the study. * Patients who are receiving medications known to prolong QTc interval are not eligible. * Patients who are receiving therapeutic anticoagulation with warfarin or other coumadin-derived anticoagulants are not eligible. Therapy with heparin, low molecular weight heparin (LMWH), or fondaparinux is allowed as long as the patient has adequate coagulation defined as aPTT \< 1.5Xs ULN and INR \< 1.5.
• Patients who have an uncontrolled infection are not eligible.
• Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study are not eligible.
• Patients with known clinically significant active malabsorption syndrome or other condition that could affect absorption are not eligible.
• Patients with prior or ongoing clinically significant medical or psychiatric condition that, in the investigator's opinion, could affect the safety of the subject, or could impair the assessment of study results are not eligible.
Inclusion Criteria:
• Inclusion criteria already met to enroll on TarGeT-SCR (central molecular and histopathologic screening) based on:
• 1) Age: patients must be ≥12 months and ≤39 years of age at the time of enrollment on TarGeT-SCR. For the Part 1 Initial Feasibility Cohort (receiving ribociclib and everolimus) only: patients must be \<21 years of age at the time of enrollment on this protocol.
• 2) Diagnosis: patients with newly-diagnosed HGG, including DIPG are eligible. All patients must have histologic confirmation tumor tissue from diagnostic biopsy or resection, without exceptions. The diagnosis of HGG, including DIPG, must have been confirmed through TarGeT-SCR: * For the diagnosis of DIPG, patients must have a tumor with pontine epicenter and diffuse involvement of at least 2/3 of the pons, with histopathology, consistent with diffuse WHO grade 2-4 glioma * All other HGGs must be WHO grade 3 or 4.
• 3) Disease status: There are no disease status requirements for enrollment * Patients without measurable disease are eligible. * Patients with metastatic or multifocal disease or gliomatosis cerebri who received upfront CSI are eligible * Patients with a primary spinal HGG are eligible * Patients with secondary, radiation-related HGG are eligible.
• Inclusion criteria for assignment to TarGeT-A, for all strata:
• 1) Presence of at least one relevant actionable somatic alteration, detailed here: * Pathogenic alterations presumed to cause activation of cell cycle: * Amplification of CDK4 or CDK6 * Deletion of CDKN2A, CDKN2B, or CDKN2C * Amplification of CCND1 or CCND2 * Pathogenic alterations presumed to cause activation of the PI3K/mTOR pathway: * Deletion or mutation of PTEN * Mutation or amplification of PIK3CA * Mutation of PIK3R1 * Deletion or mutation of TSC1 or TSC2 * Patients with evidence of homozygous (biallelic) RB1 loss by sequencing are excluded from TarGeT-A * Patients whose tumors harbor other alterations suspected to activate the cell cycle and/or PI3K/mTOR pathway could potentially also be eligible, but only following consensus recommendation by the international multidisciplinary molecular screening committee. * For Stratum E: H3G34 (R/V) mutation
• 2) Performance Level: Karnofsky ≥ 50% for patients \> 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of ag. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
• 3) Prior Therapy for HGG: * Surgery, RT, dexamethasone are permissible. Temozolomide administered concurrently with RT is permissible. Avastin/bevacizumab use is permitted given the last dose was administered \> 21 days prior to enrollment. No other prior anticancer therapy for HGG will be allowed. * Patients must have received photon or proton RT. * Patients must have started RT \< 42 calendar days from initial diagnosis defined as the date of diagnostic biopsy or resection. If a patient underwent 2 upfront surgeries (e.g., biopsy then resection or debulking), this is the date of the second surgery. * RT delivered via photon or proton beam, must have been administered at a standard dose including (54 Gy in 30 fractions for DIPG, 54-59.4 Gy in 30-33 fractions), 45 Gy-54 Gy for primary spinal disease, and/or 36 Gy-39.6 Gy craniospinal for patients with spinal or leptomeningeal metastatic disease with supplemental boost to 45-54 Gy for metastasis within the thecal sac and 54 Gy-60 Gy for intracranial metastasis. Any variances in the radiotherapy dose within 10% of the standard doses outlined above will be discussed with the Sponsor-Investigator to confirm eligibility prior to study enrollment. * Patients must enroll and start treatment No later than 35 calendar days post-completion of RT. The earliest patients can begin protocol treatment is 28 calendar days post-completion of RT.
• 4) Organ Function Requirements
• 4.1) Adequate Bone Marrow Function Defined as: * Peripheral absolute neutrophil count (ANC) ≥ 1000/mm3 * Platelet count ≥ 100,000/mm3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) * Hemoglobin \>8 g/dL (may be transfused)
• 4.2) Adequate Renal Function Defined as: * Creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73 m2 OR * Maximum serum creatinine based on (Schwartz et al. J. Peds, 106:522, 1985) age/gender as follows: 1 to \< 2 years=0.6 mg/dL for males and females; 2 to \< 6 years=0.8 mg/dL for males and females; 6 to \< 10 years= 1.0 mg/dL for males and females; 10 to \< 13 years=1.2 mg/dL for males and females. 13 to \< 16 years=1.5 mg/dL for males and 1.4 mg/dL for females.
• 4.3) Adequate Liver Function Defined as: * Total bilirubin must be ≤ 1.5 times institutional upper limit of normal for age * AST(SGOT)/ALT(SGPT) ≤ 3 times institutional upper limit of normal * Serum albumin ≥ 2g/dL
• 4.4) Adequate Cardiac Function Defined as: * Ejection fraction of ≥ 50% by echocardiogram * QTc ≤ 450 msec (by Bazett formula)
• 4.5) Adequate Neurologic Function Defined as: Patients with seizure disorder may be enrolled if well-controlled on anticonvulsants that are not strong inducers or inhibitors of CYP3A4/5.
• 4.6) Adequate Pulmonary Function Defined as: No evidence of dyspnea at rest, and a pulse oximetry \>94% on room air if there is clinical indication for determination.
• 5) Ability to take medications by mouth: For ribociclib and everolimus strata, patients must be able to take study medications by mouth as administration via NG/NJ/G tube is not allowed.
• 6) Informed Consent: All patients and/or their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines
• 7) Contraception: Male and female patients of childbearing potential must be willing to use a highly effective contraception method. Exclusion Criteria
• Pregnant or Breast-Feeding Pregnant or breast-feeding women will not be entered on this study due to known potential risks of fetal and teratogenic adverse events as seen in animal/human studies. Pregnancy tests must be obtained in girls who are post-menarchal. Patients of childbearing or child fathering potential must agree to use at least one highly effective method of contraception while being treated on this study and for 3 months after completing therapy. A woman is considered of childbearing potential if she is fertile, following menarche and until becoming post-menopausal unless permanently sterile. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. A man is considered fertile after puberty unless permanently sterile by bilateral orchidectomy. Male participants should refrain from sperm donation throughout the duration of treatment and for 3 months after completion of therapy A highly effective contraception method is defined as one that results in a low failure rate (\<1% per year) when used consistently and correctly. The following are considered highly effective contraception methods: * Combined estrogen and progesterone containing hormonal contraception associated with inhibition of ovulation. * Progesterone-only hormonal contraception associated with inhibition of ovulation. * Intra Uterine Device (IUD) * Intra Uterine hormone releasing system * Bilateral tubal occlusion * Vasectomized partner * Sexual abstinence (avoiding having heterosexual intercourse) The following contraceptive measures are NOT considered effective * Progesterone-only hormonal contraception (birth control pill) that that does NOT stop ovulation * Male or female condom with or without spermicide * Cap, diaphragm or sponge with spermicide
• Concomitant Medications * Patients receiving corticosteroids are eligible. The use of corticosteroids must be reported. * Patients who are currently receiving another investigational drug are not eligible. * Patients who are currently receiving other anti-cancer agents are not eligible, with the exception of temozolomide given concurrently with RT only. * Patients who are receiving enzyme inducing anticonvulsants that are strong inducers or inhibitors of CYP3A4/5 are not eligible. * Patients who are receiving strong inducers or inhibitors of CYP3A4/5 are not eligible and should be avoided from 14 days prior to enrollment to the end of the study. * Patients who are receiving medications known to prolong QTc interval are not eligible. * Patients who are receiving therapeutic anticoagulation with warfarin or other coumadin-derived anticoagulants are not eligible. Therapy with heparin, low molecular weight heparin (LMWH), or fondaparinux is allowed as long as the patient has adequate coagulation defined as aPTT \< 1.5Xs ULN and INR \< 1.5.
• Patients who have an uncontrolled infection are not eligible.
• Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study are not eligible.
• Patients with known clinically significant active malabsorption syndrome or other condition that could affect absorption are not eligible.
• Patients with prior or ongoing clinically significant medical or psychiatric condition that, in the investigator's opinion, could affect the safety of the subject, or could impair the assessment of study results are not eligible.
DRUG: Ribociclib, DRUG: Everolimus, DRUG: Temozolomide (TMZ)
High Grade Glioma, Diffuse Intrinsic Pontine Glioma, Anaplastic Astrocytoma, Glioblastoma, Glioblastoma Multiforme, Diffuse Midline Glioma, H3 K27M-Mutant, Metastatic Brain Tumor, WHO Grade III Glioma, WHO Grade IV Glioma, Diffuse Hemispheric Glioma, H3 G34-Mutant
Pediatric Dose Optimization for Seizures in Emergency Medical Services (PediDOSE)
Lauren Riney - lauren.riney@cchmc.org
ALL
6 months to 13 years old
PHASE3
NCT05121324
Inclusion Criteria:
* Witnessed by the paramedic to be actively seizing, regardless of seizure type or duration; AND
* Under the care of a paramedic; AND
* Transported by an EMS agency participating in the study
Exclusion Criteria:
* A prior history of a benzodiazepine allergy; OR
* Known or presumed pregnancy; OR
* Severe growth restriction based on the paramedic's subjective assessment DRUG: Standardized seizure protocol, DRUG: Conventional seizure protocol
Seizures
Child, Emergency Medical Services
Spastic Paraplegia - Centers of Excellence Research Network (SP-CERN)
Karlee Migneault - Karlee.Migneault@cchmc.org
ALL
NCT06553976
Inclusion Criteria:
* Male or female patients of all ages with a clinical and molecular diagnosis of hereditary spastic paraplegia type 4 (SPG4, SPAST) or hereditary spastic paraplegia type 5A (SPG5A, CYP7B1).
Exclusion Criteria:
* Not having such a diagnosis and/or not being related to such individual. Hereditary Spastic Paraplegia, Primary Lateral Sclerosis, SPG4, SPG5A, Spastic Paraplegia 4, Spastic Paraplegia 5A, Early Onset Hereditary Spastic Paraplegia, Neuromuscular Diseases, Spastic Paraplegia, Hereditary
A Phase 2, Open-Label Study to Evaluate the Safety and Effects of HLX-1502 in Patients With Neurofibromatosis Type 1 (INSPIRE-NF1)
Lori Backus - lori.backus@cchmc.org
ALL
12 years and over
PHASE2
NCT06541847
Inclusion Criteria:
• All participants must have a diagnosis of NF1 based on the 2021 revised consensus criteria.
• Participants must have PN(s) that are progressive OR are causing significant morbidity, such as (but not limited to) head and neck lesions that are compromising the airway or great vessels, brachial or lumbar plexus lesions that are causing nerve compression and loss of function, lesions causing significant disfigurement (e.g., orbital lesions), lesions of the extremity that cause limb hypertrophy or loss of function, and painful lesions. Participants with paraspinal PN will be eligible for this trial. Histologic confirmation of tumor is not necessary but should be considered if there are clinical or radiographic findings concerning for malignant transformation of a PN.
• Measurable Disease: Participants must have measurable PN(s) amenable to volumetric MRI analysis. For the purpose of this study, the target lesion must be seen on at least 3 consecutive MRI slices and the field of view must contain the entire tumor of interest. Tumors must be at least 3 mL in volume (most PN 3 cm in longest diameter will meet this criteria). If the tumor is \< 3 cm in longest diameter, the participant may still be eligible. Central review of the MRI of the target PN is required prior to enrollment to ensure that the tumor is measurable and amenable to volumetric analysis.
• Age: Participants must be ≥ 12 years of age at the time of study entry. Note: Although prior MEKi therapy is not a requirement, patients should be counseled on the availability of FDA-approved MEKi therapies prior to enrollment.
• Weight ≥ 42 kg.
• Performance Level: Participants must have a Lansky (12-15 years of age) or Karnofsky (16+ years of age) score ≥ 50%.
• Organ Function Requirements: Adequate Bone Marrow Function, Adequate Renal Function, Adequate Liver Function, Normal pancreatic function: amylase and lipase levels ≤ 1.5 x ULN. Blood pressure within upper limit of normal as defined below based on the average of the 2nd and 3rd of a total of 3 consecutive measurements, 5 minutes apart. Antihypertensives are permissible to achieve blood pressure within ULN, however must be on stable antihypertensive regimen with no adjustments within 14 days of enrollment.
• Sexually active women of childbearing potential and fertile male participants and their partners must agree to use effective methods of contraception e.g., hormonal oral contraception, injectables, intrauterine device, surgical sterilization including vasectomy, or hormonal implant with barrier methods (male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 4 months after the last dose of study treatment. Barrier methods alone are insufficient. True sexual abstinence or evidence of surgical sterility (e.g. vasectomized partner, post-hysterectomy, menopause with last menstrual period \>=12 months prior to screening visit) are acceptable method of birth control. Persons of childbearing potential will be given a pregnancy test within 14 days prior to first dose of study treatment and must have a negative urine or serum pregnancy test.
• The participant is not planning to undergo surgery or other interventions/ treatments for the target lesion, except protocol specified therapy, for the duration of the study.
• The participant or the participant's legal authorized representative is able to understand the informed consent form describing the risks of the study and voluntarily signs the informed consent document.
• In the opinion of the investigator, the participant is willing and able to attend study visits, comply with the study procedures as specified in the protocol, and comply with the administration of the study drug.
Exclusion Criteria:
• Prior treatment with HLX-1502 for a PN.
• The participant has used any of the following systemic medications/ therapies within the specified period prior to enrollment: MEK-inhibitors, other drugs in the TKI class, HLX-1502, Participants may have received treatment for a PN or other tumor/malignancy but must have fully recovered to baseline or CTCAE ≤ Grade 1 from acute toxicities from prior therapies except alopecia, Myelosuppressive chemotherapy, Hematopoietic growth factors, Biologic (anti-neoplastic agent), Investigational Drugs, Any other systemically administered anti-neoplastic agent and Radiation therapy.
• Evidence of an NF1-related tumor such as optic pathway or other low-grade glioma, high-grade glioma, malignant peripheral nerve sheath tumor, or other cancer/tumor requiring treatment with chemotherapy, biologic therapy, surgery or radiation therapy.
• Participants with high-grade glioma, malignant peripheral nerve sheath tumor, or other malignancy who received treatment in the last 12 months. Exceptions include basal cell carcinoma of the skin and squamous cell carcinoma of the skin that have undergone potentially curative therapy. If the investigator has any clinical concerns for ANNUBP/Atypical Neurofibroma or MPNST, a biopsy sample must be taken prior to study confirming eligibility.
• Dental braces or prosthesis that interfere with volumetric analysis of the neurofibroma(s).
• Surgery: Any major surgery within 12 weeks before starting the Treatment Period or foreseen during participation in the trial, any minor surgeries within 1 month before first dose of study treatment and Participants must have complete wound healing from major surgery or minor surgery before the first dose of study treatment. Participants with clinically relevant ongoing complications from prior surgery are not eligible.
• Cataracts noted on ophthalmologic exam.
• Cardiovascular disorders.
• Other clinically significant disorders that would preclude safe study participation, including active infection, a known history of HIV seropositivity or known immunodeficiency or Known history of Hepatitis B or Hepatitis C.
• Participants who require treatment with a drug that is a substrate of CYP1A2, CYP2C8, UGT1A1, UGT1A3 with a narrow therapeutic index during protocol therapy.
• Known severe sensitivity to HLX-1502 or any excipient of HLX-1502 or history of allergic reactions attributed to compounds of similar chemical or biologic composition to HLX-1502.
• Known severe sensitivity to FD\&C Yellow No. 5.
• Participants receiving therapeutic anticoagulation with vitamin K antagonist.
• Participants presently with iron deficiency and/or actively receiving iron replacement or requiring treatment with copper or zinc for any indication at study baseline.
• Pregnant or breast-feeding women.
• Unable or unwilling to swallow tablets.
• Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter ingestion and/or the absorption of HLX-1502.
• Participants who have other medical, social or concurrent challenges that are likely to negatively impact their ability to meet all of the trial obligations and therefore may increase the risk of safe participation in the study.
DRUG: HLX-1502
Neurofibromatosis Type 1
Neurofibromatosis Type 1, Plexiform Neurofibroma, pediatric
Regulating Together in Tuberous Sclerosis Complex (RT)
Molly Griffith - molly.griffith@cchmc.org
ALL
8 years to 17 years old
NA
NCT06105736
Inclusion Criteria:
* Children ages 8-17 years inclusive with a documented clinical and/or genetic diagnosis of TSC and exhibiting symptoms of behavioral dysregulation (identified on the TAND Checklist having temper tantrums, aggressive outbursts, self-injury, and/or impulsivity) are eligible for inclusion.
Additional inclusion/eligibility criteria include:
* Participants and their caregivers have access to a computer, phone, or tablet with video capability and stable internet connection. If lack of a device or internet service is the sole barrier to eligibility/participation, interested individuals will be connected to a TSC Clinic social worker to link them to existing government and charity programs specifically addressing this disparity in underserved communities and households in need (e.g., the Affordable Connectivity Program).
* Participants must also be willing to participate in treatment sessions and have minimal levels of functional verbal communication (child and their caregiver must be fluent in English
* Child must have a minimum IQ\>65 on the WASI-II at the screening/baseline visit).
Exclusion Criteria:
* Participants be on a stable medication regimen at least 4 weeks prior to enrollment
* Do not have a plan to start a new psychosocial intervention (e.g., individual psychotherapy, family psychotherapy, group psychotherapy or social skills training) or behavior medication within 30 days prior to enrollment or at any point during the study. ----Participants with significant disruptive, aggressive, self-injurious or sexually inappropriate behaviors deemed potentially dangerous or overly disruptive to the group dynamic/session, having significant co-occurring neuropsychiatric illness warranting other treatment approaches as determined by study clinician (e.g., substance use disorders, psychotic disorders, schizophrenia), or having significant sensory impairment that would limit participation in intervention curriculum/materials (e.g., blindness or uncorrected hearing loss) also will be excluded. BEHAVIORAL: Behavioral Intervention in a small group platform
TSC, Behavioral Symptoms
Child and Adolescent Registry for Participants With Narcolepsy
Melodie Boh - melodie.boh@cchmc.org
ALL
Up to 17 years old
NCT04899947
Inclusion Criteria:
* Any child or adolescent with a physician-confirmed diagnosis of narcolepsy
* Age less than 18 years
* Willing to participate in the Registry and complete the informed consent form
* Able to participate in English based registry
Exclusion Criteria:
* Age 18 years or more
* Fail to complete the informed consent form Narcolepsy
Rett Syndrome Registry (RSR)
Andrea Gonnella - Andrea.Gonnella@cchmc.org
ALL
0 years to 99 years old
NCT05432349
Inclusion Criteria:
* Male or female with a pathologic loss of function alteration of MECP2
Exclusion Criteria:
* Male or female with a gain of function alteration of MECP2, including those with MEPC2 duplication or triplication Rett Syndrome, Rett Syndrome, Atypical, Genetic Disease, Genetic Diseases, X-Linked, Intellectual Disability, Neurobehavioral Manifestations, Neurologic Manifestations, Neurologic Disorder, Neurodevelopmental Disorders, Nervous System Diseases
Rett syndrome, MECP2, Neurodevelopmental disorder, Registry, Natural History Study
Prospective Research Rare Kidney Stones (ProRKS) (ProRKS)
Prasad Devarajan - prasad.devarajan@cchmc.org
ALL
NCT02780297
Inclusion Criteria:
• Diagnosis of primary hyperoxaluria
• Diagnosis of enteric hyperoxaluria
• Diagnosis of Dent Disease
• Diagnosis of Cystinuria
• Diagnosis of adenine phosphoribosyltransferase deficiency (APRTd)
• Diagnosis of Lowe Syndrome
• Diagnosis of Dent Disease Carrier
Exclusion Criteria:
• Prior renal failure
• History of liver and/or kidney transplant.
Hyperoxaluria, Cystinuria, Dent Disease, Lowe Syndrome, Adenine Phosphoribosyltransferase Deficiency
primary hyperoxaluria, Dent Disease, enteric hyperoxaluria, cystinuria, Lowe Syndrome, Adenine phosphoribosyltransferase deficiency, PH, APRTd, APRT, hyperoxaluria, oxalate, oxalosis, PH type 1, PH type 2, PH type 3, Dents, Dent, Dent 1, Dent 2, APRT deficiency
Gene Therapy Trial for Otoferlin Gene-mediated Hearing Loss
Sawvell Katie - katie.sawvell@cchmc.org
ALL
PHASE3
NCT05821959
Criteria for Inclusion:
• Participants may be of any age, based on Cohort Criteria
• At least two mutations in the otoferlin gene
• Clinical presentation of Profound (Part A) or Severe to Profound (Parts B, C, and D) bilateral sensorineural hearing loss as assessed by ABR
• Preserved distortion product otoacoustic emissions (DPOAEs)
• Able and willing to comply with all study requirements, including willingness to participate in a separate long term follow-up study after completion of this trial Criteria for Exclusion:
• Persistent ear infections, anatomic or other abnormalities of the ear, and/or medical conditions that would contraindicate undergoing surgery, anesthesia, and/or administration of investigational gene therapy
• Cochlear Implant(s) in the ear(s) to receive AAVAnc80-hOTOF
• Prior participation in a clinical trial with an investigational drug, within six months prior to administration, or any prior participation in a gene therapy clinical trial (with the exception of AK-OTOF-101 for Part D participants)
• Participants may be of any age, based on Cohort Criteria
• At least two mutations in the otoferlin gene
• Clinical presentation of Profound (Part A) or Severe to Profound (Parts B, C, and D) bilateral sensorineural hearing loss as assessed by ABR
• Preserved distortion product otoacoustic emissions (DPOAEs)
• Able and willing to comply with all study requirements, including willingness to participate in a separate long term follow-up study after completion of this trial Criteria for Exclusion:
• Persistent ear infections, anatomic or other abnormalities of the ear, and/or medical conditions that would contraindicate undergoing surgery, anesthesia, and/or administration of investigational gene therapy
• Cochlear Implant(s) in the ear(s) to receive AAVAnc80-hOTOF
• Prior participation in a clinical trial with an investigational drug, within six months prior to administration, or any prior participation in a gene therapy clinical trial (with the exception of AK-OTOF-101 for Part D participants)
COMBINATION_PRODUCT: AAVAnc80-hOTOF via Akouos Delivery Device, COMBINATION_PRODUCT: AAVAnc80-hOTOF via Akouos Delivery Device and Precision Delivery Mechanism
Sensorineural Hearing Loss, Bilateral
Otoferlin, Auditory neuropathy (AN), Deafness, autosomal recessive 9 (DFNB9), Hearing loss, Hearing loss, bilateral, Hearing loss, sensorineural
Descartes-08 for Children, Adolescents, and Young Adults With Autoimmune Disorders
Alexandra Duell - alexandra.duell@cchmc.org
ALL
12 years and over
PHASE1
NCT07089121
Inclusion Criteria:
* At least age 12
* definitive diagnosis of childhood-onset systemic lupus erythematous, juvenile Myasthenie gravis, juvenile dermatomyositis and AAV
* Signs and symptoms of moderate disease
* History of systemic treatment
* Parent/Guardian/Patient must be able to give written informed consent
Exclusion Criteria:
* Major chronic illness that is not well managed at the time of study entry and in the opinion of the investigator may increase the risk to the patient;
* Abnormal PT/INR or PTT increased \> 1.5-fold or patient is on anticoagulation therapy (except in cases of elevated PTT with documented lupus anticoagulant; or in patients who have been on stable doses of anticoagulation therapy for more than 6 months of VTE diagnosis; or in patients on stable doses of anticoagulation therapy for at least 8 weeks of atrial fibrillation diagnosis; these conditions will not be exclusionary unless, in the investigator's opinion, they make participation in the study unsafe);
* ANC \< 1000 cells/microliter ;
* Hemoglobin \< 8.0 g/dL ;
* Platelets \< 50,000/mm3 (NOTE: platelet transfusions are permissible);
* ALT and/or AST with GGT ≥ 3× upper limit of normal
* Creatine Clearance less than 30mL/min /1.73 m2;
* History of primary immunodeficiency, organ, or allogeneic bone marrow transplant;
* Patients must be seronegative for hepatitis B surface antigen;
* Patients must be seronegative for hepatitis C antibody. If hepatitis C antibody test is positive, then patients must be tested for the presence of viremia by RT-PCR and must be HCV RNA negative;
* History of positive HIV or positive HIV at screening;
* Active tuberculosis or positive QuantiFERON test at screening;
* Any other laboratory abnormality that, in the opinion of the investigator, may jeopardize the subject's ability to participate in the study; 23. Any active significant cardiac or pulmonary disease not related to the primary indication as determined by principal investigator and medical monitor Note: Patients with asthma and COPD controlled with inhaled medications are allowed; 24. Any arterial or venous thromboembolic events in the past 3 months; 25. History of malignancy that required treatment in the past 3 years except for successfully-treated squamous cell and/or basal cell carcinoma of the skin and/or breast or colon cancer that is surgically removed and did not require adjuvant chemotherapy or radiotherapy; 26. Treatment with any investigational agent within 4 weeks of screening or 5 half-lives of the investigational drug (whichever is longer); 27. Receipt of a live vaccination within 4 weeks prior to baseline (Day 1) or intent to receive live vaccination during the study (Note: mRNA-based vaccines such as those against SARS-CoV-2 are not considered live; likewise, the Janssen Covid-19 vaccine is not live); 28. History of significant recurrent infections or any active infection that may interfere with the patient's participation in the opinion of the investigator; 29. Any known psychiatric illness that may interfere with the patient's participation in the study in the opinion of the investigator. DRUG: Descartes-08
Childhood-onset Systemic Lupus Erythematous, ANCA-Associated Vasculitis (AAV), Juvenile Myasthenia Gravis, Juvenile Dermatomyositis
A Study to Evaluate the Efficacy and Safety of Cannabidiol Oral Solution (CBD-OS [GWP42003-P, JZP926]) for the Treatment of Focal-Onset Seizures
Katie Hall - Katie.Hall@cchmc.org
ALL
12 years to 75 years old
PHASE1
NCT07233239
Participants are eligible to be included in the main study only if all of the following criteria apply:
• Participant has a documented diagnosis of focal epilepsy according to the ILAE Classification of Epilepsy, 2017, characterized by focal seizure types with typical interictal/ictal EEG findings (eg, history of an EEG with focal sharp waves or slowing). Participants with a documented diagnosis of focal epilepsy and a normal EEG are eligible for inclusion.
• Participant is currently treated with at least 1, but no more than 4, antiseizure medications on a stable regimen.
• Participant is aged 12 to 75 years old, inclusive, at Screening. Participants are excluded from the study if any of the following criteria apply:
• Has a concurrent, confirmed diagnosis of non-epileptic seizures or events that can confound the assessment of the efficacy measures, in the opinion of the investigator.
• Has clinically significant unstable medical condition(s), other than epilepsy.
• History of suicidal behavior, current suicidal risk as determined from history, or presence of active suicidal ideation as indicated by a positive response to Item 4 or Item 5 on the C-SSRS or is considered at risk of suicide or self-harm based on the clinical judgement of the investigator following interview with the participant and/or caregiver.
• Has known or suspected hypersensitivity to cannabinoids or any of the excipients of the study intervention, such as sesame oil.
• Is currently treated with Epidiolex or received treatment with Epidiolex within 28 days prior to Screening (Visit 1).
• Is currently using or has used recreational or medicinal cannabis, cannabinoid/CBD based medications, products, or supplements (botanical or synthetic) within 28 days prior to Screening (Visit 1) and/or is unwilling to abstain for the duration of the study.
• Presence of only nonmotor focal aware seizures or primary generalized epilepsies.
• Participant has a documented diagnosis of focal epilepsy according to the ILAE Classification of Epilepsy, 2017, characterized by focal seizure types with typical interictal/ictal EEG findings (eg, history of an EEG with focal sharp waves or slowing). Participants with a documented diagnosis of focal epilepsy and a normal EEG are eligible for inclusion.
• Participant is currently treated with at least 1, but no more than 4, antiseizure medications on a stable regimen.
• Participant is aged 12 to 75 years old, inclusive, at Screening. Participants are excluded from the study if any of the following criteria apply:
• Has a concurrent, confirmed diagnosis of non-epileptic seizures or events that can confound the assessment of the efficacy measures, in the opinion of the investigator.
• Has clinically significant unstable medical condition(s), other than epilepsy.
• History of suicidal behavior, current suicidal risk as determined from history, or presence of active suicidal ideation as indicated by a positive response to Item 4 or Item 5 on the C-SSRS or is considered at risk of suicide or self-harm based on the clinical judgement of the investigator following interview with the participant and/or caregiver.
• Has known or suspected hypersensitivity to cannabinoids or any of the excipients of the study intervention, such as sesame oil.
• Is currently treated with Epidiolex or received treatment with Epidiolex within 28 days prior to Screening (Visit 1).
• Is currently using or has used recreational or medicinal cannabis, cannabinoid/CBD based medications, products, or supplements (botanical or synthetic) within 28 days prior to Screening (Visit 1) and/or is unwilling to abstain for the duration of the study.
• Presence of only nonmotor focal aware seizures or primary generalized epilepsies.
DRUG: CBD-OS
Focal Seizures
Focal Seizures
Clinical Course Of Disease In Participants With FA-CM
Jaynee.Bartsch@cchmc.org
ALL
6 years and over
NCT06865482
Inclusion Criteria:
* Male or female, ages ≥6 years at the time of signing the informed consent (and assent, if applicable).
* Diagnosis of FA, based on clinical phenotype and genotype (GAA expansion on both alleles or compound heterozygous), with onset of FA occurring at ≤25 years of age
* Confirmed left ventricular hypertrophy (LVH)
* Left ventricular ejection fraction ≥30%
Exclusion Criteria:
* Presence of other form(s) of CM contributing to heart failure (HF), clinically significant cardiac anatomic abnormality or congenital cardiac malformation, clinically significant coronary artery, uncorrected, hemodynamically significant primary structural valvular disease not due to CM
* Currently receiving intermittent or continuous intravenous (IV) inotrope infusion, presence of a ventricular assist device, or history of prior heart transplantation
* Contraindication to cMRI, participants \<12 years of age who cannot complete the cMRI without sedation will instead undergo ECHOs and are exempt from this criterion.
* Prior organ transplantation
* Initiation of cardiac resynchronization therapy (CRT) within 6 months prior to screening.
* History of prior gene transfer or cell therapy.
* Poorly controlled diabetes (hemoglobin A1c ≥8%)
* Active hematologic or solid organ malignancy Friedreich Ataxia, Cardiomyopathy
Friedreich Ataxia, FA-CM, Cardiomyopathy, FA, Cardiac Disease
A Study of EPX-100 (Clemizole Hydrochloride) in Participants With Dravet Syndrome (ARGUS)
Samantha Ballard - samantha.ballard@cchmc.org
ALL
2 years and over
PHASE3
NCT04462770
Key
• Male and female participants 2 years and older at time of consent.
• Participant or parent/legally authorized representative (LAR) willing and able to provide written informed consent and assent (if applicable) prior to initiation of any study related procedures.
• Clinical diagnosis of DS. Participants must have seizures which are not completely controlled by AEDs with the following criteria: * Onset of seizures prior to 18 months of age, * Normal development at onset, * History of at least one type of countable motor seizure (CMS), * Brain MRI without cortical malformation (not including mild atrophy associated with the natural progression of DS), * Genetic mutation of the SCN1A gene must be documented. Key
• Known sensitivity, allergy, or previous exposure to clemizole HCl.
• Exposure to any investigational drug or device \<90 days prior to Screening or plans to participate in another drug or device trial at any time during the study.
• Seizures secondary to illicit drug (this includes concomitant use of tetrahydrocannabinol \[THC\] and nonprescription cannabidiol preparations) or alcohol use, infection, neoplasm, demyelinating disease, degenerative neurological disease, or central nervous system disease deemed progressive, metabolic illness, or progressive degenerative disease.
• Concurrent use of lorcaserin. Note: Prior use of lorcaserin is permitted if at least 30 days have passed since the last dose.
• Concurrent use of fenfluramine.
• Epilepsy surgery planned during the study or epilepsy surgery within 6 months prior to Screening.
Inclusion Criteria:
• Male and female participants 2 years and older at time of consent.
• Participant or parent/legally authorized representative (LAR) willing and able to provide written informed consent and assent (if applicable) prior to initiation of any study related procedures.
• Clinical diagnosis of DS. Participants must have seizures which are not completely controlled by AEDs with the following criteria: * Onset of seizures prior to 18 months of age, * Normal development at onset, * History of at least one type of countable motor seizure (CMS), * Brain MRI without cortical malformation (not including mild atrophy associated with the natural progression of DS), * Genetic mutation of the SCN1A gene must be documented. Key
Exclusion Criteria:
• Known sensitivity, allergy, or previous exposure to clemizole HCl.
• Exposure to any investigational drug or device \<90 days prior to Screening or plans to participate in another drug or device trial at any time during the study.
• Seizures secondary to illicit drug (this includes concomitant use of tetrahydrocannabinol \[THC\] and nonprescription cannabidiol preparations) or alcohol use, infection, neoplasm, demyelinating disease, degenerative neurological disease, or central nervous system disease deemed progressive, metabolic illness, or progressive degenerative disease.
• Concurrent use of lorcaserin. Note: Prior use of lorcaserin is permitted if at least 30 days have passed since the last dose.
• Concurrent use of fenfluramine.
• Epilepsy surgery planned during the study or epilepsy surgery within 6 months prior to Screening.
DRUG: Clemizole HCl, DRUG: Placebo
Dravet Syndrome
Clemizole hydrochloride, Convulsive seizure, Pediatric epilepsy, Dravet syndrome
Animal Assisted Therapy After Pediatric Brain Injury: Mediators and Moderators of Treatment Response.
Megan Narad - megan.narad@cchmc.org
ALL
4 years to 24 years old
NA
NCT05250180
Inclusion Criteria:
* Diagnosis: Participants must be admitted to the inpatient rehabilitation unit for treatment of an acquired brain injury (TBI, brain tumor, infection, etc).
* Consent: The family must provide informed consent by parents or legal guardians.
* Assent: The child/adolescent must provide a signature indicating assent to participate in the study.
* Age at the time of screening: 4-21 years old
* Sex: includes both males and females
* Responsiveness: Rancho score greater than 2 at the time of enrollment (as noted in the medical chart).
Exclusion Criteria:
* Allergies: Patient has a significant allergy to dogs
* Fear: Patient has a significant fear of dogs
* Disease: Participant is on contact precautions or has a communicable disease that may pose a risk to the dog or dog handler or has a compromised immune system where interacting with the dog and/or handler would be of significant risk to the patient.
* Medical History: History of developmental delay prior to ABI.
* Behavioral History: Participant or family has a history of animal abuse or cruelty.
* Responsiveness: Rancho score of 2 or less OTHER: Animal Assisted Therapy, OTHER: Control
Brain Injuries
Pediatric brain injury, Animal assisted therapy, inpatient rehabilitation
Observation Study in Patients Age 0-5 Years With LAMA2-related Congenital Muscular Dystrophy
Jessica Getz - Jessica.getz@cchmc.org
ALL
Up to 5 years old
NCT06503367
Inclusion Criteria:
* Signed informed consent by the subject, parent(s) or legally authorized representative (LAR) and/or assent by the subject (when applicable).
* Subject must be aged birth to less than 5.0 years of age at time of consent.
* A confirmed diagnosis of LAMA2-RD confirmed via:
a: Two pathogenic variants in the LAMA2 gene (via a CLIA-approved laboratory) or: b. muscle biopsy with absence of merosin (laminin-211) and at least one pathogenic variant in the LAMA2 gene
* Absence of another confirmed genetic disease.
* Willingness to maintain current exercise and/or physical therapy regimen for the duration of the clinical study.
* Willingness to comply with the study protocol, including but not limited to, all study procedures and visits.
Exclusion Criteria:
* Acute medical illness or hospitalization within 30 days prior to informed consent.
* Participation in a previous trial of any investigational agent for LAMA2-RD within 1 month prior to informed consent, or use of any other investigational therapy (including off-label use of Losartan) within 30 days prior to informed consent, or participation in other clinical studies, within 30 days (or 3 half-lives, whichever is longer) prior to informed consent, which in the opinion of the PI, may potentially confound results from this study.
* Other significant medical condition, which in the opinion of the site Principal Investigator may confound interpretation of the clinical course of LAMA2- RD. LAMA2-MD \(Merosin Deficient Congenital Muscular Dystrophy, MDC1A\)
Early Phase 1, Observational, Natural History, Neuromuscular, Functional Assessments
RASopathy Biorepository
Lindsey Aschbacher-Smith - lindsey.aschbacher-smith@cchmc.org
ALL
NCT04395495
Inclusion Criteria:
* Patients with a suspected or known diagnosis of any of the group of disorders known as RASopathies (e.g., Neurofibromatosis, Costello Syndrome, Noonan Syndrome). Diagnosis may be made clinically and/or confirmed through genetic testing.
* Unaffected relatives of patients with a suspected or known diagnosis of any of the group of disorders known as RASopathies.
Exclusion Criteria:
* Individuals who do not have a suspected or definite diagnosis of a RASopathy.
* Individuals who do not have a relative with a suspected or definite diagnosis of a RASopathy.
* Patients who do not have the ability/capacity to undergo the informed consent process OR whose parent/legal guardian is unable to undergo the informed consent process. RAS Mutation, Neurofibromatosis 1, Noonan Syndrome, Noonan Syndrome With Multiple Lentigines, Noonan Neurofibromatosis Syndrome, Cardiofaciocutaneous Syndrome, Costello Syndrome, Legius Syndrome, Smith-Kingsmore Syndrome, MTOR Gene Mutation, GATOR-1 Gene Mutation, SYNGAP1-Related Intellectual Disability, DLG4, MAPK1 Gene Mutation
Lutathera for Treatment of Recurrent or Progressive High-Grade CNS Tumors
- cancer@cchmc.org
ALL
4 years to 39 years old
PHASE1
NCT05278208
All participants must meet the following inclusion and exclusion criteria. No exceptions will be given. Imaging studies to establish eligibility must be done within three weeks prior to enrollment. All other clinical evaluations to establish eligibility (except for \[68Ga\]Ga-DOTATATE PET) must be done within 7 days prior to enrollment.
• Screening Criteria
• 1 Diagnosis Patient must have a diagnosis of primary high-grade CNS tumor (any histopathologic diagnosis that is WHO grade III-IV) or meningioma (any histologic grade) that is recurrent, progressive, or refractory. Note that patients with DIPG (based on radiographic/clinical diagnosis) who have undergone biopsy will be eligible with histologic diagnosis of grade II-IV infiltrating glioma. All tumors must have histologic verification either at the time of diagnosis or recurrence, except for patients meningioma who have not previously undergone biopsy or resection. Note: Refractory disease is defined as the presence of persistent abnormality on conventional MRI that is further distinguished by histology (biopsy or sample of lesion) or advanced imaging, OR as determined by the treating physician and discussed with the primary investigator prior to enrollment.
• 2 Prior Therapy Patients must have recurred/progressed following prior standard therapy for their tumor. Note: Patients with meningioma, atypical meningioma, or anaplastic meningioma must have received at least surgical resection or radiation.
• 3 Screening Consent Participant/legal guardian is willing to sign a screening consent for \[68Ga\]Ga-DOTATATE PET imaging. The screening consent is to be obtained according to institutional guidelines. Assent, when appropriate, will be obtained according to institutional guidelines.
• Eligibility Criteria * Phase I Age Patient must be ≥ 4 and \<12 years of age at the time of enrollment. Disease Status: Patients who participate in the efficacy expansion cohort must have bi-dimensionally measurable disease, defined as at least one lesion that can be accurately measured in at least two dimensions Patients with measurable extraneural disease only are also eligible. * Phase II Age Patient must be 12 to \ • Inclusion Criteria
• 1 Uptake on \[68Ga\]Ga-DOTATATE PET Patients must have uptake on DOTATATE PET/CT in at least one tumor lesion (corresponding to known disease) equivalent to a Krenning score ≥2 (confirmed by central radiology review).
• 2 Prior Therapy Patients must have recovered from the acute treatment related toxicities (defined as ≤ grade 1 if not defined in eligibility criteria) of all prior chemotherapy, immunotherapy, radiotherapy, or any other treatment modality prior to entering this study.
• 3 Chemotherapy Patients must have received their last dose of known myelosuppressive anticancer therapy at least 21 days prior to enrollment or at least 42 days if nitrosourea.
• 4 Investigational/Biologic Agent ●Biologic or investigational agent (anti-neoplastic): Patient must have recovered from any acute toxicity potentially related to the agent and received their last dose of the investigational or biologic agent ≥ 7 days prior to study enrollment. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. ●Monoclonal Antibodies and agents with known prolonged half-lives: Patient must have recovered from any acute toxicity potentially related to the agent and received their last dose of the agent ≥ 28 days prior to study enrollment.
• 5 Radiation Patients must have had their last fraction of: * Craniospinal irradiation or total body irradiation or radiation to \> 50% of pelvis \> 3 months prior to enrollment. * Focal irradiation \> 4 weeks prior to enrollment
• 6 Stem Cell Transplant Patient must be: * ≥ 6 months since allogeneic stem cell transplant prior to enrollment with no evidence of active graft vs. host disease * ≥ 3 months since autologous stem cell transplant prior to enrollment
• 7 Growth Factors Patients must be off all colony-forming growth factor(s) for at least 1 week prior to enrollment (e.g. filgrastim, sargramostim or erythropoietin). Two weeks must have elapsed if patients received long-acting formulations.
• 8 Thrombopoietin receptor agonist * Phase I: Patients must be off thrombopoietin receptor agonists for at least 1 week prior to enrollment (e.g. romiplostim, eltrombopag) * Phase II: Patients can receive concurrent thrombopoietin receptor agonists
• 9 Somatostatin analogs Patients must be off long-acting somatostatin analogs for at least 4 weeks and off short-acting somastatin analogs (i.e., octreotide) for at least 24 hours.
• 10 Neurologic Status * Patients with neurological deficits should have deficits that are stable for a minimum of 1 week prior to enrollment, documented by a detailed neurological exam. * Patients with seizure disorders may be enrolled if seizures are well controlled.
• 11 Performance Status Karnofsky Performance Scale (KPS for \> 16 years of age) or Lansky Performance Score (LPS for ≤ 16 years of age) assessed within two weeks of enrollment must be ≥ 50. Patients who are unable to walk because of neurologic deficits, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
• 12 Organ Function Patients must have adequate organ and marrow function, for eligibility and enrollment, as defined below: * Adequate Bone Marrow Function as defined as: * Absolute neutrophil count ≥ 1.0 x 109 cells/ L * Platelets ≥100 x 109 cells/ L (unsupported, defined as no platelet transfusion within 7 days) * Hemoglobin ≥8 g/dl (may receive transfusions) * Adequate Renal Function as defined as: * Creatinine clearance or radioisotope GFR \>70mL/min/1.73m2 OR * A serum creatinine based on (Schwartz et al. J. Peds, 106:522, 1985) age/gender as follows: 1 to \< 2 years: maximum serum creatinine 0.6 mg/dL for males and females. 2 to \< 6 years: maximum serum creatinine 0.8 mg/dL for males and females. 6 to \< 10 years: maximum serum creatinine 1.0 mg/dL for males and females. 10 to \< 13 years: maximum serum creatinine 1.2 mg/dL for males and females. 13 to \< 16 years: maximum serum creatinine 1.5 mg/dL for males and 1.4 mg/dL for females. ≥ 16 years: maximum serum creatinine 1.7 mg/dL for males and 1.4 mg/dL for females. * Adequate Liver Function as defined as: * Total bilirubin ≤ 3 times institutional upper limit of normal (ULN) for age * AST(SGOT)/ALT(SGPT) ≤ 3 times institutional ULN * Serum albumin ≥ 2g/dL * Coagulation parameters: INR \<1.5 times ULN and aPTT \<1.5 times ULN unless patients are receiving therapeutic anticoagulation which affects these parameters * Adequate Cardiac Function as defined as: * Ejection fraction of ≥ 55% by echocardiogram * Serum electrolytes (Sodium, Potassium, Chloride) within institutional limits of normal (patients can be on enteral supplementation)
• 13 Corticosteroids Patients who are receiving dexamethasone must be on a stable or decreasing dose for at least 1 week prior to enrollment, with a maximum dexamethasone dose of 2.5mg/m2/day.
• 14 Pregnancy Status Female patients of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• 15 Pregnancy Prevention Patients of childbearing or child fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study and for at least 7 months after drug cessation in females of childbearing potential and for at least 4 months after drug cessation in males of child fathering potential.
• 16 Informed Consent The patient or parent/guardian is able to understand the consent and is willing to sign a written informed consent document according to institutional guidelines.
• Exclusion Criteria
• 1 Confirmed bone marrow metastatic disease Patients with confirmed metastatic disease to bone marrow are ineligible.
• 2 Presence of bulky disease Patients with bulky disease on imaging as described below are ineligible. Treating physicians are encouraged to request a rapid central imaging review to confirm fulfillment of these criteria if there are questions or concerns. Bulky disease is defined as: * Tumor with evidence of clinically significant uncal herniation or midline shift. * Tumor with diameter of \>5cm in one dimension on T2/FLAIR. * Tumor that in the opinion of the site investigator shows significant mass effect in either the brain or spine. Note that patients with metastatic or multi-focal disease (with exception of bone marrow) are eligible as long as no sites of disease meet above criteria for bulky disease.
• 3 Breast-feeding Nursing mothers are excluded from this study. There is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with Lutathera.
• 4 Concurrent Illness * Patients with a history of any other malignancy, except patients with a secondary brain tumor if the patient's prior malignancy has been in remission for at least 5 years from the end of treatment. * Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the opinion of the investigator would compromise the patient's ability to tolerate protocol therapy, put them at additional risk for toxicity or would interfere with the study procedures or results. * Patients with type I diabetes.
• 5 Concomitant Medications * Patients who are receiving any other anti-cancer or investigational drug therapy are ineligible. * Prior or current treatment with 177Lu-DOTATATE/TOC or 90Y-DOTATATE/TOC.
• 6 Prisoners will be excluded from this study.
• 7 Inability to participate: Patients who in the opinion of the investigator are unwilling or unable to return for required follow-up visits, obtain follow-up studies required to assess toxicity to therapy, or adhere to drug administration plan, other study procedures, and study restrictions.
• Inclusion of Women and Minorities Both males and females of all races and ethnic groups are eligible for this study.
• Screening Criteria
• 1 Diagnosis Patient must have a diagnosis of primary high-grade CNS tumor (any histopathologic diagnosis that is WHO grade III-IV) or meningioma (any histologic grade) that is recurrent, progressive, or refractory. Note that patients with DIPG (based on radiographic/clinical diagnosis) who have undergone biopsy will be eligible with histologic diagnosis of grade II-IV infiltrating glioma. All tumors must have histologic verification either at the time of diagnosis or recurrence, except for patients meningioma who have not previously undergone biopsy or resection. Note: Refractory disease is defined as the presence of persistent abnormality on conventional MRI that is further distinguished by histology (biopsy or sample of lesion) or advanced imaging, OR as determined by the treating physician and discussed with the primary investigator prior to enrollment.
• 2 Prior Therapy Patients must have recurred/progressed following prior standard therapy for their tumor. Note: Patients with meningioma, atypical meningioma, or anaplastic meningioma must have received at least surgical resection or radiation.
• 3 Screening Consent Participant/legal guardian is willing to sign a screening consent for \[68Ga\]Ga-DOTATATE PET imaging. The screening consent is to be obtained according to institutional guidelines. Assent, when appropriate, will be obtained according to institutional guidelines.
• Eligibility Criteria * Phase I Age Patient must be ≥ 4 and \<12 years of age at the time of enrollment. Disease Status: Patients who participate in the efficacy expansion cohort must have bi-dimensionally measurable disease, defined as at least one lesion that can be accurately measured in at least two dimensions Patients with measurable extraneural disease only are also eligible. * Phase II Age Patient must be 12 to \ • Inclusion Criteria
• 1 Uptake on \[68Ga\]Ga-DOTATATE PET Patients must have uptake on DOTATATE PET/CT in at least one tumor lesion (corresponding to known disease) equivalent to a Krenning score ≥2 (confirmed by central radiology review).
• 2 Prior Therapy Patients must have recovered from the acute treatment related toxicities (defined as ≤ grade 1 if not defined in eligibility criteria) of all prior chemotherapy, immunotherapy, radiotherapy, or any other treatment modality prior to entering this study.
• 3 Chemotherapy Patients must have received their last dose of known myelosuppressive anticancer therapy at least 21 days prior to enrollment or at least 42 days if nitrosourea.
• 4 Investigational/Biologic Agent ●Biologic or investigational agent (anti-neoplastic): Patient must have recovered from any acute toxicity potentially related to the agent and received their last dose of the investigational or biologic agent ≥ 7 days prior to study enrollment. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. ●Monoclonal Antibodies and agents with known prolonged half-lives: Patient must have recovered from any acute toxicity potentially related to the agent and received their last dose of the agent ≥ 28 days prior to study enrollment.
• 5 Radiation Patients must have had their last fraction of: * Craniospinal irradiation or total body irradiation or radiation to \> 50% of pelvis \> 3 months prior to enrollment. * Focal irradiation \> 4 weeks prior to enrollment
• 6 Stem Cell Transplant Patient must be: * ≥ 6 months since allogeneic stem cell transplant prior to enrollment with no evidence of active graft vs. host disease * ≥ 3 months since autologous stem cell transplant prior to enrollment
• 7 Growth Factors Patients must be off all colony-forming growth factor(s) for at least 1 week prior to enrollment (e.g. filgrastim, sargramostim or erythropoietin). Two weeks must have elapsed if patients received long-acting formulations.
• 8 Thrombopoietin receptor agonist * Phase I: Patients must be off thrombopoietin receptor agonists for at least 1 week prior to enrollment (e.g. romiplostim, eltrombopag) * Phase II: Patients can receive concurrent thrombopoietin receptor agonists
• 9 Somatostatin analogs Patients must be off long-acting somatostatin analogs for at least 4 weeks and off short-acting somastatin analogs (i.e., octreotide) for at least 24 hours.
• 10 Neurologic Status * Patients with neurological deficits should have deficits that are stable for a minimum of 1 week prior to enrollment, documented by a detailed neurological exam. * Patients with seizure disorders may be enrolled if seizures are well controlled.
• 11 Performance Status Karnofsky Performance Scale (KPS for \> 16 years of age) or Lansky Performance Score (LPS for ≤ 16 years of age) assessed within two weeks of enrollment must be ≥ 50. Patients who are unable to walk because of neurologic deficits, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
• 12 Organ Function Patients must have adequate organ and marrow function, for eligibility and enrollment, as defined below: * Adequate Bone Marrow Function as defined as: * Absolute neutrophil count ≥ 1.0 x 109 cells/ L * Platelets ≥100 x 109 cells/ L (unsupported, defined as no platelet transfusion within 7 days) * Hemoglobin ≥8 g/dl (may receive transfusions) * Adequate Renal Function as defined as: * Creatinine clearance or radioisotope GFR \>70mL/min/1.73m2 OR * A serum creatinine based on (Schwartz et al. J. Peds, 106:522, 1985) age/gender as follows: 1 to \< 2 years: maximum serum creatinine 0.6 mg/dL for males and females. 2 to \< 6 years: maximum serum creatinine 0.8 mg/dL for males and females. 6 to \< 10 years: maximum serum creatinine 1.0 mg/dL for males and females. 10 to \< 13 years: maximum serum creatinine 1.2 mg/dL for males and females. 13 to \< 16 years: maximum serum creatinine 1.5 mg/dL for males and 1.4 mg/dL for females. ≥ 16 years: maximum serum creatinine 1.7 mg/dL for males and 1.4 mg/dL for females. * Adequate Liver Function as defined as: * Total bilirubin ≤ 3 times institutional upper limit of normal (ULN) for age * AST(SGOT)/ALT(SGPT) ≤ 3 times institutional ULN * Serum albumin ≥ 2g/dL * Coagulation parameters: INR \<1.5 times ULN and aPTT \<1.5 times ULN unless patients are receiving therapeutic anticoagulation which affects these parameters * Adequate Cardiac Function as defined as: * Ejection fraction of ≥ 55% by echocardiogram * Serum electrolytes (Sodium, Potassium, Chloride) within institutional limits of normal (patients can be on enteral supplementation)
• 13 Corticosteroids Patients who are receiving dexamethasone must be on a stable or decreasing dose for at least 1 week prior to enrollment, with a maximum dexamethasone dose of 2.5mg/m2/day.
• 14 Pregnancy Status Female patients of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• 15 Pregnancy Prevention Patients of childbearing or child fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study and for at least 7 months after drug cessation in females of childbearing potential and for at least 4 months after drug cessation in males of child fathering potential.
• 16 Informed Consent The patient or parent/guardian is able to understand the consent and is willing to sign a written informed consent document according to institutional guidelines.
• Exclusion Criteria
• 1 Confirmed bone marrow metastatic disease Patients with confirmed metastatic disease to bone marrow are ineligible.
• 2 Presence of bulky disease Patients with bulky disease on imaging as described below are ineligible. Treating physicians are encouraged to request a rapid central imaging review to confirm fulfillment of these criteria if there are questions or concerns. Bulky disease is defined as: * Tumor with evidence of clinically significant uncal herniation or midline shift. * Tumor with diameter of \>5cm in one dimension on T2/FLAIR. * Tumor that in the opinion of the site investigator shows significant mass effect in either the brain or spine. Note that patients with metastatic or multi-focal disease (with exception of bone marrow) are eligible as long as no sites of disease meet above criteria for bulky disease.
• 3 Breast-feeding Nursing mothers are excluded from this study. There is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with Lutathera.
• 4 Concurrent Illness * Patients with a history of any other malignancy, except patients with a secondary brain tumor if the patient's prior malignancy has been in remission for at least 5 years from the end of treatment. * Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the opinion of the investigator would compromise the patient's ability to tolerate protocol therapy, put them at additional risk for toxicity or would interfere with the study procedures or results. * Patients with type I diabetes.
• 5 Concomitant Medications * Patients who are receiving any other anti-cancer or investigational drug therapy are ineligible. * Prior or current treatment with 177Lu-DOTATATE/TOC or 90Y-DOTATATE/TOC.
• 6 Prisoners will be excluded from this study.
• 7 Inability to participate: Patients who in the opinion of the investigator are unwilling or unable to return for required follow-up visits, obtain follow-up studies required to assess toxicity to therapy, or adhere to drug administration plan, other study procedures, and study restrictions.
• Inclusion of Women and Minorities Both males and females of all races and ethnic groups are eligible for this study.
DRUG: LUTATHERA® (Lutetium Lu 177 dotatate)
High Grade Glioma, Meningioma, Embryonal Tumor, Medulloblastoma, Anaplastic Ependymoma, Recurrent Diffuse Intrinsic Pontine Glioma, Recurrent Malignant Glioma, Recurrent Medulloblastoma, Recurrent Primary Central Nervous System Neoplasm, Refractory Diffuse Intrinsic Pontine Glioma, Refractory Malignant Glioma, Refractory Medulloblastoma, Refractory Primary Central Nervous System Neoplasm
Somatostatin Receptor, DOTATATE, Lutathera
Tuberous Sclerosis Complex and Lymphangioleiomyomatosis Pregnancy Registry (TSC-LAM Registry)
Molly Griffith - molly.griffith@cchmc.org
FEMALE
NCT06160310
Inclusion Criteria:
* A pregnant woman with a clinical or genetic diagnosis of TSC as determined by the 2021 Consensus Guidelines (1)
* A pregnant woman with a diagnosis of LAM
* A pregnant woman with a variant of uncertain significance in TSC 1 or TSC 2
* A pregnant woman who is pregnant and the fetus has a 50% chance of TSC as deemed by the PI or Sub-Is
* A pregnant woman whose fetus is found to have concern for TSC secondary to rhabdomyomas, tubers, or congenital subependymal giant cell astrocytoma.
* An infant born to an enrolled individual.
Exclusion Criteria:
* A pregnant woman without TSC who has used preimplantation genetic testing for TSC unless qualifies under inclusion criteria #4.
* Infants diagnosed with TSC whose birth mother was not enrolled. Tuberous Sclerosis Complex, Lymphangioleiomyomatosis
Tuberous Sclerosis Complex, TSC, Lymphangioleiomyomatosis, LAM
Autism Doula Program Evaluation
Teresa Smith, PhD - teresa.smith@cchmc.org
ALL
18 months to 71 months old
NA
NCT06896942
Inclusion Criteria:
caregivers of children who are 18 months to five years and recently diagnosed with autism. Caregivers must identify as Black and be over the age of 18 and identify their children as Black. OTHER: Autism Doula, OTHER: DDBP Family Navigation
Health Equity, Autism Spectrum Disorder
health equity, autism spectrum disorder, family navigation
Alpha Auditory Entrainment for Cognitive Enhancement and Sensory Hypersensitivity in Youth With Developmental Disorders (ENTRAIN)
Jae Citarella - Jae.Citarella@cchmc.org
ALL
5 years to 10 years old
NA
NCT06227780
Inclusion Criteria:
* FXS Cohort: 1) Aged 5-10 years, inclusive; 2) Patient has full FMR1 mutation confirmed by genetic testing.
* ASD Cohort: 1) Aged 5-10 years, inclusive; 2) Have no known genetic mutation; 3) Have documentation of ASD diagnosis; 4) Score ≤ 15 on SCQ screen; 5) Be in good health per investigator.
* TDC Cohort: 1) Aged 5-10 years, inclusive; 2) Have no known genetic mutation; 3) Have documentation of ASD diagnosis; 4) Score ≤ 15 on SCQ screen; 5) Be in good health per investigator; 6) Patient has met normal developmental milestones; Patient has no family history of heritable neuropsychiatric disorders; 7) Patient has an IQ greater than 85 on the Stanford-Binet; 8) Score ≤8 on an SCQ screen.
Exclusion Criteria:
* All subjects: 1) Patient has auditory or visual impairments that cannot be corrected; 2) History of substance abuse or dependence within the past 6 months OTHER: Alpha Auditory Entrainment, OTHER: Sham
Fragile X Syndrome, Autism Spectrum Disorder, Autistic Disorder, Asperger Syndrome
Neurodevelopmental Disorders, Autistic Disorder, Autism Spectrum Disorder, Fragile X Syndrome, Fragile X, FXS, ASD, Asperger, Autism
Phase 1 Dose-escalating Study of MM-398 (Irinotecan Sucrosofate Liposome Injection) Plus Intravenous Cyclophosphamide in Recurrent or Refractory Pediatric Solid Tumors
- cancer@cchmc.org
ALL
12 months to 20 years old
PHASE1
NCT02013336
Inclusion Criteria:
* Histologically or cytologically-confirmed Ewing sarcoma, rhabdomyosarcoma, neuroblastoma, or osteosarcoma
* Disease progression after prior therapy in locally advanced or metastatic setting
* Measurable or evaluable disease based on the Response Evaluation Criteria in Solid Tumors (RECIST v1.1) criteria
* Age 12 months to \<21 years
* Adequate bone marrow reserves, hepatic function, and renal function
* Recovered from effects of any prior surgery or cancer therapy
* Patients 18 years or older will provide written consent. A parent or legal guardian of a patient \<18 years of age will provide informed consent and patients 11 to 18 years of age will provide written assent or as per participating institutional policy.
Exclusion Criteria:
* Clinically significant gastrointestinal disorders
* NYHA Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure
* Active infection or unexplained fever
* Known hypersensitivity to any of the components of MM-398 or other liposomal products
* Recent Investigational therapy
* Pregnant or breast feeding; females of child-bearing potential must test negative for pregnancy at the time of enrollment DRUG: MM-398 (Irinotecan Sucrosofate Liposome Injection) plus cyclophosphamide
Recurrent or Refractory Solid Tumors, Ewing Sarcoma, Rhabdomyosarcoma, Neuroblastoma, Osteosarcoma
pediatric, MM-398, cyclophosphamide, irinotecan
Study of S-606001 as an Add-on to Enzyme Replacement Therapy (ERT) in Participants With Late-onset Pompe Disease (LOPD)
Laurie Bailey - Laurie.Bailey@cchmc.org
ALL
18 years and over
PHASE2
NCT07123155
Key
• Deficiency of acid alpha-glucosidase (GAA) enzyme
• GAA genotype * Participant has a %FVC ≥30% and ≤80% in an upright position without mechanical ventilation at screening; or Participant has ≥10% %FVC drop from upright position to supine position and %FVC ≥20% in a supine position. * Participant performs the 6MWT at screening, as determined by the clinical evaluator, and meets all of the following criteria:
• Screening values of 6-minute walk distance (6MWD) are ≥75 meters
• Screening values of 6MWD are ≤90% of the predicted value for healthy adults * Participants must be ERT-experienced, defined as currently receiving ERT and having been receiving ERT for ≥24 months, with no regimen change in the last 6 months. Key
Inclusion Criteria:
* Participant must be ≥18 years of age and ≥40 kilograms (kg) of body weight at the time of signing the informed consent.
* Participant must have a diagnosis of LOPD based on documentation of 1 of the following:
• Deficiency of acid alpha-glucosidase (GAA) enzyme
• GAA genotype * Participant has a %FVC ≥30% and ≤80% in an upright position without mechanical ventilation at screening; or Participant has ≥10% %FVC drop from upright position to supine position and %FVC ≥20% in a supine position. * Participant performs the 6MWT at screening, as determined by the clinical evaluator, and meets all of the following criteria:
• Screening values of 6-minute walk distance (6MWD) are ≥75 meters
• Screening values of 6MWD are ≤90% of the predicted value for healthy adults * Participants must be ERT-experienced, defined as currently receiving ERT and having been receiving ERT for ≥24 months, with no regimen change in the last 6 months. Key
Exclusion Criteria:
* Has a medical condition or any other extenuating circumstance that may pose an undue safety risk to the participant or may compromise his/her ability to comply with or adversely impact protocol requirements.
* Has active infections at screening.
* Malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.
* Current or chronic history of liver disease.
* Known biallelic loss of function mutations whether in glycogenin gene (GYG) or in glycogen phosphorylase muscle associated gene(PYGM) .
* Has received any investigational therapy or pharmacological treatment for Pompe disease, within 30 days or 5 half-lives of the therapy or treatment, whichever is longer, before day 1 or is anticipated to do so during the study.
* Has received gene therapy or small interfering ribonucleic acid (RNA) therapy for Pompe disease.
* Participant, if female, is pregnant or breastfeeding at screening.
* Participant, whether male or female, is planning to conceive a child during the study.
Note: Other protocol-specified inclusion and exclusion criteria may apply. DRUG: S-606001, DRUG: Placebo
Pompe Disease
Late-onset Pompe disease, Enzyme replacement therapy, LOPD, ERT, S-606001, Muscle glycogen synthase, Liver glycogen synthase, Rare disease, Autosomal disease, Acid alpha-glucosidase, GAA, Glycogen storage disorder, GSD
Tegavivint for the Treatment of Recurrent or Refractory Solid Tumors, Including Lymphomas and Desmoid Tumors
- cancer@cchmc.org
ALL
12 months to 30 years old
PHASE1
NCT04851119
Inclusion Criteria:
* PART A: Patients must be \>= 12 months and =\< 21 years of age at the time of study enrollment
* PART B: Patients must be \>= 12 months and =\< 30 years of age at the time of study enrollment
* Patients with recurrent or refractory solid tumors including non-Hodgkin lymphoma and desmoid tumors are eligible. Patients must have had histologic verification of malignancy at original diagnosis or relapse
* PART A: Patients with relapsed or refractory solid tumors, including patients with non-Hodgkin lymphoma and desmoid tumors
* PART B: Patients with recurrent or refractory Ewing sarcoma, desmoid tumors, osteosarcoma, liver tumors (HCC and hepatoblastoma), Wilms tumor, and tumors with Wnt pathway aberrations. For the Wnt pathway aberrations cohort we will include the most common CTNNB1 mutations (S37F, S45F, T41A, S45P, S33C, S37C, D32Y, S33F, T41I, G34R, G34V, D32N, S33P, G34E, D32G) as well as any loss of function mutations in the APC, Axin2FBXW7, TCF7L2, and RNF43 genes or any gain-of-function mutations in the GSK3B, LRP6, and LGR5 genes. For patients without prior sequencing, immunohistochemistry (IHC), is required. IHC showing strong nuclear beta-catenin staining will be accepted for the following tumor types: colorectal carcinoma, melanoma, endometrial cancer, ovarian cancer, neuroblastoma, non-Hodgkin lymphoma, pancreatic ductal adenocarcinoma, and solid pseudopapillary tumor of the pancreas
* PART A: Patients must have either measurable or evaluable disease. For desmoid tumors, the patient must have disease that the investigator deems unresectable or sufficiently morbid or potentially life-threatening that there is favorable risk/benefit to the patient to participate in the trial
* PART B: Patients must have measurable disease. For desmoid tumors, the patient must have measurable disease that the investigator deems unresectable or sufficiently morbid or potentially life-threatening that there is favorable risk/benefit to the patient to participate in the trial
* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients \> 16 years of age and Lansky for patients =\< 16 years of age
* Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the numerical eligibility criteria are met, e.g., blood count criteria, the patient is considered to have recovered adequately.
* Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive
* Solid tumor patients: \>= 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea)
* Non-Hodgkin lymphoma patients
* A waiting period prior to enrollment is not required for patients receiving standard maintenance chemotherapy (i.e., corticosteroid, vincristine, thioguanine \[6MP\], and/or methotrexate)
* \>= 14 days must have elapsed after the completion of other cytotoxic therapy, with the exception of hydroxyurea, for patients not receiving standard maintenance therapy
* NOTE: Cytoreduction with hydroxyurea must be discontinued \>= 24 hours prior to the start of protocol therapy
* Anti-cancer agents not known to be myelosuppressive (e.g., not associated with reduced platelet or absolute neutrophil counts \[ANC\]): \>= 7 days after the last dose of agent
* Antibodies: \>= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =\< 1
* Corticosteroids: If used to modify immune adverse events related to prior therapy, \>= 14 days must have elapsed since last dose of corticosteroid
* Hematopoietic growth factors: \>= 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or 7 days for short acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur
* Interleukins, interferons and cytokines (other than hematopoietic growth factors): \>= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
* Stem cell Infusions (with or without total-body irradiation \[TBI\]):
* Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: \>= 84 days after infusion and no evidence of graft versus host disease (GVHD)
* Autologous stem cell infusion including boost infusion: \>= 42 days.
* Cellular therapy: \>= 42 days after the completion of any type of cellular therapy (e.g., modified T cells, natural killer \[NK\] cells, dendritic cells, etc.).
* External beam radiation therapy (XRT)/external beam irradiation including protons: \>= 14 days after local XRT; \>= 150 days after TBI, craniospinal XRT or if radiation to \>= 50% of the pelvis; \>= 42 days if other substantial bone marrow (BM) radiation
* Radiopharmaceutical therapy (e.g., radiolabeled antibody, iobenguane I-131 \[131I MIBG\]): \>= 42 days after systemically administered radiopharmaceutical therapy
* Patients must not have received prior exposure to tegavivint
* PATIENTS WITH SOLID TUMORS WITHOUT KNOWN BONE MARROW INVOLVEMENT: Peripheral absolute neutrophil count (ANC) \>= 1000/uL (within 7 days prior to enrollment)
* PATIENTS WITH SOLID TUMORS WITHOUT KNOWN BONE MARROW INVOLVEMENT: Platelet count \>= 100,000/uL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) (within 7 days prior to enrollment)
* PATIENTS WITH SOLID TUMORS WITHOUT KNOWN BONE MARROW INVOLVEMENT: Hemoglobin \>= 8.0 g/dL at baseline (may receive red blood cell \[RBC\] transfusions) (within 7 days prior to enrollment)
* Patients with known bone marrow metastatic disease will be eligible for study provided they meet blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions). These patients will not be evaluable for hematologic toxicity. At least 5 of every cohort of 6 patients must be evaluable for hematologic toxicity for the dose-escalation part of the study. If dose-limiting hematologic toxicity is observed, all subsequent patients enrolled on Part A must be evaluable for hematologic toxicity
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 or a creatinine based on age/gender as follows (within 7 days prior to enrollment):
* Age; maximum serum creatinine
* Age 1 to \< 2 years; 0.6 mg/dL (male); 0.6 mg/dL (female)
* Age 2 to \< 6 years; 0.8 mg/dL (male); 0.8 mg/dL (female)
* Age 6 to \< 10 years; 1 mg/dL (male); 1 mg/dL (female)
* Age 10 to \< 13 years; 1.2 mg/dL (male); 1.2 mg/dL (female)
* Age 13 to \< 16 years; 1.5 mg/dL (male); 1.4 mg/dL (female)
* Age \>= 16 years; 1.7 mg/dL (male); 1.4 mg/dL (female)
* PATIENTS WITH SOLID TUMORS: Bilirubin (sum of conjugated + unconjugated or total) =\< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment)
* PATIENTS WITH SOLID TUMORS: Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 135 U/L. For the purpose of this study, the ULN for SGPT is 45 U/L (within 7 days prior to enrollment)
* PATIENTS WITH SOLID TUMORS: Albumin \>= 2 g/dL (within 7 days prior to enrollment)
Exclusion Criteria:
* Pregnant or breast-feeding women will not be entered on this study because there is yet no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use two effective methods of birth control, including a medically accepted barrier or contraceptive method (e.g., male or female condom) for the duration of the study. Abstinence is an acceptable method of birth control
* Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible. If used to modify immune adverse events related to prior therapy, \>= 14 days must have elapsed since last dose of corticosteroid
* Patients who are currently receiving another investigational drug are not eligible
* Patients who are currently receiving other anti-cancer agents are not eligible
* Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial
* Patients who are currently receiving drugs that are strong inducers or inhibitors of CYP3A4 are not eligible. Strong inducers or inhibitors of CYP3A4 should be avoided from 14 days prior to the 1st dose of tegavivint to the end of the study
* Patients who have received bisphosphonates within 4 weeks prior to study enrollment will be excluded
* Patients who have received denosumab within 180 days prior to study enrollment will be excluded
* Patients with primary brain tumors are ineligible
* Patients with known central nervous system (CNS) metastasis, except for craniopharyngeal tumors, will be excluded
* Patients with a known metabolic bone disease (ex: hyperparathyroidism, Paget's disease, osteomalacia) are not eligible
* Patients with a disorder associated with abnormal bone metabolism will be excluded
* Patients with grade \>= 2 hypocalcemia that is not corrected with oral calcium supplementation will be excluded
* Patients with vitamin D \< 20 ng/mL will require supplementation, or will otherwise be excluded. Patients must agree to take vitamin D +/- calcium supplements (if necessary) according to institutional or published guidelines. Additional calcium supplementation is not required if adequate dietary intake can be ascertained
* Patients with pre-existing grade 3 osteoporosis are excluded
* Patients who have an uncontrolled infection are not eligible
* Patients who have received a prior solid organ transplantation are not eligible
* Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible PROCEDURE: Biospecimen Collection, PROCEDURE: Dual X-ray Absorptiometry, DRUG: Tegavivint, PROCEDURE: X-Ray Imaging
Colorectal Carcinoma, Endometrial Carcinoma, Melanoma, Neuroblastoma, Ovarian Carcinoma, Pancreatic Ductal Adenocarcinoma, Recurrent Desmoid Fibromatosis, Recurrent Ewing Sarcoma, Recurrent Hepatoblastoma, Recurrent Hepatocellular Carcinoma, Recurrent Malignant Solid Neoplasm, Recurrent Non-Hodgkin Lymphoma, Recurrent Osteosarcoma, Refractory Desmoid Fibromatosis, Refractory Ewing Sarcoma, Refractory Hepatoblastoma, Refractory Hepatocellular Carcinoma, Refractory Malignant Solid Neoplasm, Refractory Non-Hodgkin Lymphoma, Refractory Osteosarcoma, Solid Pseudopapillary Neoplasm of the Pancreas, Wilms Tumor
PEP-CMV Vaccine Targeting CMV Antigen to Treat Newly Diagnosed Pediatric HGG and DIPG and Recurrent Medulloblastoma
- cancer@cchmc.org
ALL
3 years to 39 years old
PHASE2
NCT05096481
Inclusion Criteria for patients with recurrent /progressive medulloblastoma (stratum I)
• Age: Patients must be ≥3 and ≤39 years of age at the time of study enrollment
• Diagnosis: Patients must have a diagnosis of medulloblastoma that is recurrent, progressive or refractory. All patients must have histological verification of a medulloblastoma, at original diagnosis or relapse. • Patients must have measurable disease defined as a lesion that can be measured in two perpendicular diameters on MRI.
• Metastatic Disease: Patients with M+ disease are eligible.
• Performance Status: Karnofsky ≥ 50% for patients \>16 years of age or Lansky ≥ 50 for patients ≤ 16 years of age. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
• Prior Therapy:
• Radiotherapy: prior radiotherapy requirements Patients must have received prior disease-directed therapy including radiotherapy for their initial diagnosis of medulloblastoma unless patients are less than 4 years of age at the time of enrollment. For those less than 4 years of age at the time of enrollment, prior disease directed therapy does not have to include prior radiotherapy. Patients must have had their last fraction of: * Craniospinal irradiation, total body irradiation or radiation to ≥ 50% of pelvis \> 3 months prior to enrollment. * Focal irradiation \> 4 weeks prior to enrollment
• Myelosuppressive anticancer therapy: Patients must have received their last dose of myelosuppressive anticancer therapy at least 21 days prior to enrollment
• Immunotherapy: Patients must have received their last dose of any immunotherapy agents at least 30 days prior to enrollment
• Non-myelosuppressive anticancer agents: Patients must have received their last dose of non-myelosuppressive anticancer agents at least 7 days prior to study enrollment.
• Antibodies: Patients must have received their last dose of any antibodies at least 21 days prior to enrollment.
• Hematopoietic growth factors: Patients must have received their last dose of hematopoietic growth factors at least 14 days prior to enrollment for a long-acting growth factor (e.g. pegfilgrastim) or 7 days prior to enrollment for short-acting growth factor.
• Autologous stem cell infusion: At least 90 days must have elapsed after an autologous stem cell infusion
• Organ Function Requirements:
• Adequate bone marrow function defined as: * ANC (Absolute neutrophil count) ≥ 1000/µl. * Platelets ≥ 100,000/µl. (may be supported) * Hemoglobin \> 8 g/dL. (may be supported)
• Adequate Renal Function defined as: Creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73 m2 or A serum creatinine based on age/gender as follows: Age: Maximum Serum Creatinine (mg/dL) * 2 to \< 6 years: 0.8 (Male) 0.8 (Female) * 6 to \< 10 years: 1 (Male) 1 (Female) * 10 to \< 13 years: 1.2 (Male) 1.2 (Female) * 13 to \< 16 years: 1.5 (Male) 1.4 (Female) * ≥ 16 years: 1.7 (Male) 1.4 (Female)
• Adequate Liver Function Defined as * Total bilirubin ≤1.5 times institutional ULN * AST(SGOT) ≤3 × institutional upper limit of normal * ALT(SGPT) ≤3 × institutional upper limit of normal
• Adequate Neurological Function Defined as * Patients with neurological deficits should have deficits that are stable for a minimum of 2 weeks prior to enrollment. * Patients with current seizure disorders may be enrolled if seizures are well- controlled on antiepileptic therapies.
• Patients of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study and for three months after drug cessation.
• Signed informed consent according to institutional guidelines must be obtained prior to enrollment. Inclusion Criteria for Patients with Newly-Diagnosed High-Grade Gliomas (HGG) (stratum II, CLOSED on 19Aug2026) and Newly-Diagnosed (DIPG) (stratum III)
• Age: Patients must be ≥3 and ≤39 years of age at the time of study enrollment
• Diagnosis
• Stratum II \[CLOSED on 19Aug2026\]: patients must have histologically confirmed, newly-diagnosed HGG (such as anaplastic astrocytoma, glioblastoma, H3K27-altered DMG). * Patients with a newly-diagnosed HGG must enroll within 6 weeks of their final dose of standard radiation therapy with or without chemotherapy. * Patients with primary spinal cord tumors are eligible
• Stratum III: Patients with a newly-diagnosed DIPG: * Patients with a radiographically typical DIPG, defined as a tumor with a pontine epicenter and diffuse involvement of more than 2/3 of the pons, are eligible without histologic confirmation. * Patients with brainstem lesions that do not meet these radiographic criteria will be eligible if there is histologic confirmation of an infiltrating astrocytoma WHO grades II-IV.
• Metastatic Disease: Patients with M+ disease are eligible.
• Performance Status: Karnofsky ≥ 50 for patients \> 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of age (See Appendix I). Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
• Prior Therapy requirements: Patients must have received no prior therapy other than surgery, radiation, chemotherapy during radiotherapy and/or steroids (dexamethasone with goal to wean dexamethasone throughout protocol therapy). Patients with a newly diagnosed high-grade glioma or DIPG must enroll within 6 weeks of their final dose of standard of care radiation therapy with or without chemotherapy.
• Patients with HGG or DIPG are permitted, but not required, to have received chemotherapy during radiation. Bevacizumab is permitted prior to enrollment in patients with DIPG or HGG. Patients must have received their last dose of bevacizumab at least 14 days prior to enrollment.
• For HGG patients, Patients must have received radiotherapy at a standard dose of 54-59.4 Gy in 1.8 Gy fractions for approximately 6 weeks with an acceptable variance of 10%. Radiation therapy must have begun no later than 42 days after the date definitive surgery.
• For patients with DIPG, Patients must have received radiotherapy at a standard dose of radiotherapy of 54 Gy in 1.8 Gy daily fractions for approximately 6 weeks with an acceptable variance rate of 10%. Radiation therapy must have begun no later than 42 days after the date of radiographic diagnosis or biopsy
• For patients with spinal cord HGG: Patients must have received radiotherapy at a standard dose of 45-54 Gy in 1.8 Gy fractions for approximately 6-7 weeks with an acceptable variance of 10%
• For patients with metastatic disease: Patients may have received standard dose CSI
• Organ Function Requirements:
• Adequate bone marrow function defined as • ANC (Absolute neutrophil count) ≥ 1000/µl. • Platelets ≥ 100,000/µl. (may be supported) • Hemoglobin \> 8 g/dL. (may be supported)
• Adequate Renal Function defined as: Creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73 m2 or A serum creatinine based on age/gender as follows: Age: Maximum Serum Creatinine (mg/dL) • 2 to \< 6 years: 0.8 (Male) 0.8 (Female) • 6 to \< 10 years: 1 (Male) 1 (Female) • 10 to \< 13 years: 1.2 (Male) 1.2 (Female) • 13 to \< 16 years: 1.5 (Male) 1.4 (Female) • ≥ 16 years: 1.7 (Male) 1.4 (Female)
• Adequate Liver Function Defined as: • Total bilirubin ≤1.5 times institutional ULN * AST(SGOT) ≤3 × institutional upper limit of normal * ALT(SGPT) ≤3 × institutional upper limit of normal
• Adequate Neurological Function Defined as: Patients with neurological deficits should have deficits that are stable for a minimum of 1 week prior to enrollment. d. Patients of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study. e. Signed informed consent according to institutional guidelines must be obtained prior to registration and for 3 months after drug cessation. Exclusion Criteria for all strata:
• Pregnancy or Breast-Feeding:
• Pregnant or breast-feeding women will not be entered on this study due to known or unknown risks of fetal and teratogenic adverse events as seen in animal/human studies. Pregnancy tests must be obtained in girls who are post-monarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.
• Pregnancy Prevention Patients of childbearing or child fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study and for 3 months after drug cessation.
• Study Specific:
• Active infection requiring treatment
• Patients with malignancy related to HIV or solid organ transplant: known history of HIV, HBV surface antigen positivity or positive HCV antibody are not eligible. Viral testing is not required unless clinically indicated in patients without a known history
• Known immunosuppressive disease
• Patients with active renal, cardiac (congestive cardiac failure, myocardial infarction, myocarditis), or moderate to severe pulmonary problems generally defined by need for medical intervention (e.g., oxygen, medications) and/or limiting activities of daily living (generally CTCAE Grade 2 or higher) or shortness of breath with limited exertion are not eligible. Pulmonary conditions include (but are not limited to) COPD, asthma, and hemi-pneumectomy
• Patients receiving concomitant immunosuppressive agents for medical conditions; inhaled corticosteroids for asthma are allowed.
• Patients receiving concomitant tumor-directed therapy
• Patients receiving any other investigational drug therapy.
• Patients on dexamethasone \> 0.1 mg/Kg/day up to maximum dose of 4 mg/day or equivalent.
• Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction).
• Patients with inability to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy
• Patients at high risk for imminent neurologic decline due to extensive bulk disease, midline shift, or herniation on MRI. These patients should be discussed with the study chairs.
• Age: Patients must be ≥3 and ≤39 years of age at the time of study enrollment
• Diagnosis: Patients must have a diagnosis of medulloblastoma that is recurrent, progressive or refractory. All patients must have histological verification of a medulloblastoma, at original diagnosis or relapse. • Patients must have measurable disease defined as a lesion that can be measured in two perpendicular diameters on MRI.
• Metastatic Disease: Patients with M+ disease are eligible.
• Performance Status: Karnofsky ≥ 50% for patients \>16 years of age or Lansky ≥ 50 for patients ≤ 16 years of age. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
• Prior Therapy:
• Radiotherapy: prior radiotherapy requirements Patients must have received prior disease-directed therapy including radiotherapy for their initial diagnosis of medulloblastoma unless patients are less than 4 years of age at the time of enrollment. For those less than 4 years of age at the time of enrollment, prior disease directed therapy does not have to include prior radiotherapy. Patients must have had their last fraction of: * Craniospinal irradiation, total body irradiation or radiation to ≥ 50% of pelvis \> 3 months prior to enrollment. * Focal irradiation \> 4 weeks prior to enrollment
• Myelosuppressive anticancer therapy: Patients must have received their last dose of myelosuppressive anticancer therapy at least 21 days prior to enrollment
• Immunotherapy: Patients must have received their last dose of any immunotherapy agents at least 30 days prior to enrollment
• Non-myelosuppressive anticancer agents: Patients must have received their last dose of non-myelosuppressive anticancer agents at least 7 days prior to study enrollment.
• Antibodies: Patients must have received their last dose of any antibodies at least 21 days prior to enrollment.
• Hematopoietic growth factors: Patients must have received their last dose of hematopoietic growth factors at least 14 days prior to enrollment for a long-acting growth factor (e.g. pegfilgrastim) or 7 days prior to enrollment for short-acting growth factor.
• Autologous stem cell infusion: At least 90 days must have elapsed after an autologous stem cell infusion
• Organ Function Requirements:
• Adequate bone marrow function defined as: * ANC (Absolute neutrophil count) ≥ 1000/µl. * Platelets ≥ 100,000/µl. (may be supported) * Hemoglobin \> 8 g/dL. (may be supported)
• Adequate Renal Function defined as: Creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73 m2 or A serum creatinine based on age/gender as follows: Age: Maximum Serum Creatinine (mg/dL) * 2 to \< 6 years: 0.8 (Male) 0.8 (Female) * 6 to \< 10 years: 1 (Male) 1 (Female) * 10 to \< 13 years: 1.2 (Male) 1.2 (Female) * 13 to \< 16 years: 1.5 (Male) 1.4 (Female) * ≥ 16 years: 1.7 (Male) 1.4 (Female)
• Adequate Liver Function Defined as * Total bilirubin ≤1.5 times institutional ULN * AST(SGOT) ≤3 × institutional upper limit of normal * ALT(SGPT) ≤3 × institutional upper limit of normal
• Adequate Neurological Function Defined as * Patients with neurological deficits should have deficits that are stable for a minimum of 2 weeks prior to enrollment. * Patients with current seizure disorders may be enrolled if seizures are well- controlled on antiepileptic therapies.
• Patients of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study and for three months after drug cessation.
• Signed informed consent according to institutional guidelines must be obtained prior to enrollment. Inclusion Criteria for Patients with Newly-Diagnosed High-Grade Gliomas (HGG) (stratum II, CLOSED on 19Aug2026) and Newly-Diagnosed (DIPG) (stratum III)
• Age: Patients must be ≥3 and ≤39 years of age at the time of study enrollment
• Diagnosis
• Stratum II \[CLOSED on 19Aug2026\]: patients must have histologically confirmed, newly-diagnosed HGG (such as anaplastic astrocytoma, glioblastoma, H3K27-altered DMG). * Patients with a newly-diagnosed HGG must enroll within 6 weeks of their final dose of standard radiation therapy with or without chemotherapy. * Patients with primary spinal cord tumors are eligible
• Stratum III: Patients with a newly-diagnosed DIPG: * Patients with a radiographically typical DIPG, defined as a tumor with a pontine epicenter and diffuse involvement of more than 2/3 of the pons, are eligible without histologic confirmation. * Patients with brainstem lesions that do not meet these radiographic criteria will be eligible if there is histologic confirmation of an infiltrating astrocytoma WHO grades II-IV.
• Metastatic Disease: Patients with M+ disease are eligible.
• Performance Status: Karnofsky ≥ 50 for patients \> 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of age (See Appendix I). Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
• Prior Therapy requirements: Patients must have received no prior therapy other than surgery, radiation, chemotherapy during radiotherapy and/or steroids (dexamethasone with goal to wean dexamethasone throughout protocol therapy). Patients with a newly diagnosed high-grade glioma or DIPG must enroll within 6 weeks of their final dose of standard of care radiation therapy with or without chemotherapy.
• Patients with HGG or DIPG are permitted, but not required, to have received chemotherapy during radiation. Bevacizumab is permitted prior to enrollment in patients with DIPG or HGG. Patients must have received their last dose of bevacizumab at least 14 days prior to enrollment.
• For HGG patients, Patients must have received radiotherapy at a standard dose of 54-59.4 Gy in 1.8 Gy fractions for approximately 6 weeks with an acceptable variance of 10%. Radiation therapy must have begun no later than 42 days after the date definitive surgery.
• For patients with DIPG, Patients must have received radiotherapy at a standard dose of radiotherapy of 54 Gy in 1.8 Gy daily fractions for approximately 6 weeks with an acceptable variance rate of 10%. Radiation therapy must have begun no later than 42 days after the date of radiographic diagnosis or biopsy
• For patients with spinal cord HGG: Patients must have received radiotherapy at a standard dose of 45-54 Gy in 1.8 Gy fractions for approximately 6-7 weeks with an acceptable variance of 10%
• For patients with metastatic disease: Patients may have received standard dose CSI
• Organ Function Requirements:
• Adequate bone marrow function defined as • ANC (Absolute neutrophil count) ≥ 1000/µl. • Platelets ≥ 100,000/µl. (may be supported) • Hemoglobin \> 8 g/dL. (may be supported)
• Adequate Renal Function defined as: Creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73 m2 or A serum creatinine based on age/gender as follows: Age: Maximum Serum Creatinine (mg/dL) • 2 to \< 6 years: 0.8 (Male) 0.8 (Female) • 6 to \< 10 years: 1 (Male) 1 (Female) • 10 to \< 13 years: 1.2 (Male) 1.2 (Female) • 13 to \< 16 years: 1.5 (Male) 1.4 (Female) • ≥ 16 years: 1.7 (Male) 1.4 (Female)
• Adequate Liver Function Defined as: • Total bilirubin ≤1.5 times institutional ULN * AST(SGOT) ≤3 × institutional upper limit of normal * ALT(SGPT) ≤3 × institutional upper limit of normal
• Adequate Neurological Function Defined as: Patients with neurological deficits should have deficits that are stable for a minimum of 1 week prior to enrollment. d. Patients of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study. e. Signed informed consent according to institutional guidelines must be obtained prior to registration and for 3 months after drug cessation. Exclusion Criteria for all strata:
• Pregnancy or Breast-Feeding:
• Pregnant or breast-feeding women will not be entered on this study due to known or unknown risks of fetal and teratogenic adverse events as seen in animal/human studies. Pregnancy tests must be obtained in girls who are post-monarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.
• Pregnancy Prevention Patients of childbearing or child fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study and for 3 months after drug cessation.
• Study Specific:
• Active infection requiring treatment
• Patients with malignancy related to HIV or solid organ transplant: known history of HIV, HBV surface antigen positivity or positive HCV antibody are not eligible. Viral testing is not required unless clinically indicated in patients without a known history
• Known immunosuppressive disease
• Patients with active renal, cardiac (congestive cardiac failure, myocardial infarction, myocarditis), or moderate to severe pulmonary problems generally defined by need for medical intervention (e.g., oxygen, medications) and/or limiting activities of daily living (generally CTCAE Grade 2 or higher) or shortness of breath with limited exertion are not eligible. Pulmonary conditions include (but are not limited to) COPD, asthma, and hemi-pneumectomy
• Patients receiving concomitant immunosuppressive agents for medical conditions; inhaled corticosteroids for asthma are allowed.
• Patients receiving concomitant tumor-directed therapy
• Patients receiving any other investigational drug therapy.
• Patients on dexamethasone \> 0.1 mg/Kg/day up to maximum dose of 4 mg/day or equivalent.
• Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction).
• Patients with inability to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy
• Patients at high risk for imminent neurologic decline due to extensive bulk disease, midline shift, or herniation on MRI. These patients should be discussed with the study chairs.
BIOLOGICAL: PEP-CMV, DRUG: Temozolomide, BIOLOGICAL: Tetanus Diphtheria Vaccine
High Grade Glioma, Diffuse Intrinsic Pontine Glioma, Recurrent Medulloblastoma
High Grade Glioma, Diffuse Intrinsic Pontine Glioma, Recurrent Medulloblastoma, Immunotherapy
Bowel Continence Across the Lifespan in People With Spina Bifida (BCALS)
Cassie Hulme - cassie.hulme@cchmc.org
ALL
5 years and over
NCT07390318
Inclusion Criteria:
* Minimum age 5 years old
* Myelomeningocele diagnosis
* Starting a retrograde or antegrade enema program (or switching from one enema program to the other)
* English or Spanish speaking/literate
Exclusion Criteria:
\- Other types of spinal dysraphism (e.g., lipomyelomeningocele, fatty filum) PROCEDURE: Retrograde Enema, PROCEDURE: Antegrade Enema
Spina Bifida, Neurogenic Bowel, Bowel Incontinence
retrograde enema, antegrade enema, bowel management program, bowel continence program, self-management, quality of life