StudyFinder
Search Results
345 Study Matches
Lorlatinib for Newly-Diagnosed High-Grade Glioma With ROS or ALK Fusion
Diarra Diop - diarra.diop@cchmc.org
ALL
1 year to 21 years old
EARLY_PHASE1
NCT06333899
Inclusion Criteria:
• Patients must be ≥ 12 months and ≤ 21 years of age at the time of study enrollment on TarGeT-SCR.
• Diagnosis: Patients with newly diagnosed high-grade glioma (HGG), including diffuse intrinsic pontine gliomas (DIPG), whose tumors harbor an ALK or ROS-1 fusion alteration are eligible. Patients must have had histologically verified high-grade glioma from diagnostic biopsy or resection. 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. All other HGGs must be Grade 3 or 4.
• Disease Status: Patients with disseminated DIPG or HGG are eligible only if the patient is to receive chemotherapy only, i.e. no craniospinal RT is intended to be given. MRI of spine must be performed if disseminated disease is suspected clinically by the treating physicians. Patients with primary spinal tumors are eligible only if the patient is to receive either chemotherapy or focal radiation therapy, i.e., no craniospinal RT is intended to be given. Patients with leptomeningeal disease only, with no definitive identifiable primary tumor, and documented ALK or ROS-1 fusion, must be discussed with the Study Chair on a case-by-case basis.
• Performance Level: 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: * Patients must not have received any prior anti-cancer chemotherapy. * Prior use of corticosteroids is allowed (see below Exclusion Criteria)
• Organ Function Requirements 6.1 Adequate Bone Marrow Function Defined as: * Peripheral absolute neutrophil count (ANC) ≥ 1000/μL * Platelet count ≥ 100,000/μL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) * Hemoglobin \>8 g/dL (may receive transfusions) 6.2 Adequate Renal Function Defined as: * Serum creatinine within normal institutional limits OR Creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73 m2 6.3 Adequate Liver Function Defined as: * Total bilirubin ≤ 2 × institutional upper limit of normal * AST(aspartate aminotransferase)/ALT(alanine transaminase) ≤ 2.5 × institutional upper limit of normal 6.4 Adequate Pulmonary Function Defined as: Pulse oximetry \> 94% on room air if there is clinical indication for determination (e.g. dyspnea at rest).
• 5Adequate Cardiac Function Defined as: QTc ≤ 470 msec (by Bazett formula) 6.6 Adequate Neurologic Function Defined as: Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled.
• 7 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:
• 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. Females of reproductive potential must use an effective non-hormonal method of contraception, since lorlatinib can render hormonal contraceptives ineffective, during study treatment and for at least 6 months after the final dose. Males with female partners of reproductive potential must use effective contraception during treatment with lorlatinib and for 3 months after the final dose.
• Concomitant Medications * Investigational Agents/Drugs: Patients who have previously received or are currently receiving another investigational drug are not eligible. * Anti-cancer Agents: Patients who have previously received or are currently receiving other anti-cancer agents, including chemotherapy, immunotherapy, monoclonal antibodies, biologic or targeted therapy, are not eligible
• Infection: Patients must not have any active, uncontrolled systemic bacterial, viral or fungal infection.
• Patients who have received prior solid organ transplantation are not eligible.
• Patients must not have malabsorption syndrome or other condition affecting oral absorption.
• Patients must not be receiving any treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor or inducer. Discontinue strong CYP3A inducers for 3 plasma half-lives of the strong CYP3A inducer prior to treatment with loraltinib. Moderate inducers of CYP3A4 should be avoided
• Avoid concomitant use of lorlatinib with certain CYP3A substrates, for which minimal concentration changes may lead to serious therapeutic failures. If concomitant use is unavoidable, increase the CYP3A substrate dosage in accordance with approved product labeling.
• P-glycoprotein (P-gp) substrates: Lorlatinib is considered a moderate P-gp inducer. Co-administration of lorlatinib with P-gp substrates including but not limited to digoxin should be avoided as the concentration of these drugs may be reduced by lorlatinib.
• 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 a known personal history of acute or chronic severe psychiatric disorders or current history of suicidal ideation and history of suicide attempt.
DRUG: Lorlatinib, DRUG: Lorlatinib with chemotherapy1, DRUG: Lorlatinib with chemotherapy 2, DRUG: Lorlatinib post Radiation
High Grade Glioma, Diffuse Intrinsic Pontine Glioma, Anaplastic Astrocytoma, Infant Type Hemispheric Glioma, Glioblastoma, Glioblastoma Multiforme, WHO Grade III Glioma, WHO Grade IV Glioma, Diffuse Midline Glioma, H3K27-altered
ALK fusion, ROS fusion, High Grade Glioma, Diffuse Intrinsic Pontine Glioma
BEATRIX: A Study to Learn About a Group B Streptococcus Vaccine in Healthy Pregnant Women and Their Babies
Natalie Brinkmann - natalie.brinkmann@cchmc.org
ALL
1 day to 49 years old
PHASE3
NCT07160244
Key Inclusion criteria- Maternal:
* Healthy pregnant women ≤49 years of age who are between 24 0/7 and 36 0/7 weeks of gestation on the day of planned vaccination, with an uncomplicated, singleton pregnancy, and who have no known increased risk of complications.
* Had a fetal anomaly ultrasound examination with no significant fetal abnormalities observed.
* Documented negative human immunodeficiency virus (HIV) antibody test, syphilis test, and hepatitis B virus (HBV) surface antigen test during this pregnancy and prior to randomization.
* Capable of giving personal signed informed consent.
* Willing to give informed consent for her infant to participate in the study.
Key Exclusion criteria- Maternal:
* Prepregnancy body mass index (BMI) of \>40 kg/m2.
* Current pregnancy complications or abnormalities that may increase the risk associated with the participation in and completion of the study.
* Prior pregnancy complications or abnormalities that, based on the investigator's judgment, may increase the risk associated with the participation in and completion of the study.
* History of microbiologically proven invasive disease caused by GBS in the current pregnancy.
* A known or suspected infection during the current pregnancy that may increase the risk of complications in pregnancy (eg, active tuberculosis, syphilis, primary genital herpes simplex, malaria).
Key Inclusion criteria- Infant Participants
\- Evidence of a signed and dated ICD signed by the parent(s)/legally authorized representative or legal guardian
Key Exclusion Criteria - Infant Participants:
\- Children or grandchildren who are direct descendants of investigator site staff or sponsor and sponsor delegate employees directly involved in the conduct of the study.
Key Exclusion Criteria - Infant immunogenicity subset Participants:
\- Children with a known or suspected contraindication to any vaccine administered in the infant vaccine immunogenicity subset.
Refer to the study contact for further eligibility details
BIOLOGICAL: Multivalent Group B streptococcus vaccine, BIOLOGICAL: Placebo, BIOLOGICAL: Infanrix hexa, BIOLOGICAL: Prevenar 20, BIOLOGICAL: Pediarix, BIOLOGICAL: Prevnar 20, BIOLOGICAL: Infanrix
Healthy
group B streptococcus, maternal immunization, vaccine
Targeted Reversal of Inflammation in Pediatric Sepsis-induced MODS (TRIPS)
Abigayle Gibson - abigayle.gibson@cchmc.org
ALL
1 day to 17 years old
PHASE2
NCT05267821
Inclusion Criteria:
* ≥ 40 weeks corrected gestational age to \< 18 years; AND
* Admission to the PICU or CICU; AND
* Onset of ≥ 2 new organ dysfunctions within the last 3 calendar days (compared to pre-sepsis baseline) as measured by the modified Proulx criteria; AND
* Documented or suspected infection as the MODS inciting event.
Exclusion Criteria:
* Weight \<3kg; OR
* Limitation of care order at the time of screening; OR
* Patients at high likelihood of progression to brain death in opinion of the clinical team; OR
* Moribund condition in which the patient is unlikely to survive the next 48 hours in opinion of the clinical team; OR
* Current or prior diagnosis of hemophagocytic lymphohistiocytosis or macrophage activation syndrome; OR
* Peripheral white blood cell count \< 1,000 cells/mm3 as the result of myeloablative therapy OR receipt of myeloablative therapy within the previous 14 days; OR
* Known allergy to anakinra, or E. coli-derived products; OR
* Known pregnancy; OR
* Lactating females; OR
* Receipt of anakinra within the previous 28 days; OR
* Resolution of MODS by MODS Day 2; OR
* Previous enrollment in the TRIPS study. DRUG: Anakinra, DRUG: Placebo
Pediatric Sepsis-induced Multiple Organ Dysfunction Syndrome (MODS)
A Study to Investigate Efficacy and Safety of Teplizumab Compared With Placebo in Participants 1 to 25 Years of Age With Stage 3 Type 1 Diabetes (βETA PRESERVE)
Cierra Farrell - cierra.farrell@cchmc.org
ALL
1 year to 25 years old
PHASE3
NCT07088068
Inclusion Criteria:
* Participants are eligible to be included in the study only if all of the following criteria apply:
* Participant must be 1 to 25 years of age inclusive, at the time of signing the informed consent.
* Participants diagnosed with T1D Stage 3 according to American Diabetes Association 2025 criteria
* Participants able to be randomized and initiate study drug within 8 weeks (56 days) of the Stage 3 T1D diagnosis
* Participants must be positive for at least one T1D autoantibody at screening:
* Glutamic acid decarboxylase (GAD-65),
* Insulinoma Antigen-2 (IA-2),
* Zinc-transporter 8 (ZnT8), or
* Insulin (if obtained not later than 14 days after exogenous insulin therapy initiation).
* Islet cell cytoplasmic autoantibodies (ICAs)
* Have random C-peptide level ≥0.2 nmol/L obtained at screening
* Enter Inclusion Criteria Sex
* Both male and female participants are eligible.
* Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
* A female participant is eligible to participate if she is not pregnant, and one of the following conditions applies:
* Is a woman of nonchildbearing potential (WONCBP) OR
* Is a woman of childbearing potential (WOCBP) and agrees to use a contraceptive method that is highly effective, with a failure rate of \<1% during the study intervention period (to be effective before starting the intervention) and for at least 30 days after the last administration of study intervention.
* A WOCBP must have a negative highly sensitive pregnancy test at screening (serum) and within 24 hours (urine or serum as required by local regulations) before the first administration of study intervention.
* Lactating woman must interrupt breastfeeding and pump and discard breast milk during and for 20 days after last administration of study intervention.
* Capable of giving signed informed consent as described in Appendix 1 of the protocol which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol.
Note: For minor participants, a specific ICF must also be signed by the participant's legally authorized representative (LAR).
Exclusion Criteria:
Participants are excluded from the study if any of the following criteria apply:
* Participant has diabetes other than autoimmune T1D that includes but is not limited to genetic forms of diabetes, maturity-onset diabetes of the young (MODY), diabetes secondary to medications or surgery and type 2 diabetes by judgement of the Investigator.
* Participant has an active serious infection and/or fever ≥38.5°C (101.3°F) within the 48 hours prior to the first dose (except if localized skin infection), or has chronic, recurrent or opportunistic infectious disease.
* At screening, participant has laboratory or clinical evidence of acute or clinically active infection with Epstein-Barr virus (EBV), cytomegalovirus (CMV).
* At screening, participant has positive serology for human immunodeficiency virus (HIV), hepatitis B (HBV), or hepatitis C (HCV).
* Participant has evidence of active or latent tuberculosis (TB) as documented by medical history and examination, chest X-rays (posterior anterior and lateral), and/or TB testing. Blood testing (eg, QuantiFERON® TB Gold test) is strongly preferred; if not available, any local approved TB test is allowed.
* Has other autoimmune diseases, (eg, rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, multiple sclerosis, systemic lupus erythematosus etc), except clinically stable autoimmune thyroid disease, or controlled celiac disease (at discretion of Investigator).
* Any clinically significant abnormality identified either in medical/surgical history or during screening evaluation (eg, physical examination, laboratory tests, vital signs), or any adverse event (AE) during screening period which, in the judgment of the investigator, would preclude safe completion of the study or constrains efficacy assessment.
* Participant has recent or planned vaccinations as follows:
* Live-attenuated (live) vaccines (eg, varicella, measles, mumps, rubella, cold-attenuated intranasal influenza vaccine, and smallpox) within the 8 weeks before first dose of the investigational medicinal product (IMP) or planned/required administration during treatment or up to 26 weeks after last IMP administration in any treatment course
* Inactivated or mRNA vaccines within 2 weeks before the first dose of IMP or planned required administration during treatment or up to 6 weeks after last IMP administration in any treatment course.
* Current or prior use (within 30 days before screening) of any anti-hyperglycemic agents other than insulin
* Past (within 30 days prior to screening) or current administration of any treatment that is known to cause a significant, ongoing change in the course of T1D or immunologic status, including but not limited to systemic corticosteroids (ie, oral, high doses of inhaled or injectable) with duration \>14 days, adrenocorticotropic hormone, verapamil).
* Past systemic immunosuppression medicine or immune modulatory biologic therapy (such as monoclonal antibodies), within 3 months or 5 half-lifes (whichever is longer) prior to dosing.
* Current or prior (within 30 days before screening) use of any medication known to significantly influence glucose tolerance (eg, atypical antipsychotics, diphenylhydantoin, niacin).
* Participant has previously received teplizumab or other anti-CD3 treatment.
* Other medications not compatible or interfering with IMP at discretion of Investigator.
* Current enrollment OR past participation in another investigational study in which an investigational intervention (eg, drug, vaccine, invasive device) was administered within the last 8 weeks or 5 half-lifes, whichever is longer, prior to screening.
* Participant has any of the following laboratory parameters, at screening prior to first dose:
* Lymphocyte count: \<1000/µL,
* Neutrophil count: \<1500/µL (\< 1000 /µL in participants with documented Duffy-null genotype),
* Platelet count: \<150,000 platelets/µL,
* Hemoglobin: \<10 g/dL,
* Aspartate aminotransferase (AST) \>2.0 × upper limit of normal (ULN),
* Alanine aminotransferase (ALT) \>2.0 × ULN,
* Total bilirubin \>1.5 × ULN with the exception of participants with the diagnosis of Gilbert's syndrome who may be eligible provided they have no other causes leading to hyperbilirubinemia
The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial. DRUG: Teplizumab, OTHER: Placebo
Type 1 Diabetes Mellitus
Checkpoint Inhibition In Pediatric Hepatocellular Carcinoma
- cancer@cchmc.org
ALL
0 years to 30 years old
PHASE2
NCT04134559
Inclusion Criteria:
* Age: Patients must be \<30 years of age at the time of study enrollment.
* Diagnosis: Patients must have relapsed/refractory, histologically confirmed HCC to be eligible for enrollment. Patients with hepatocellular neoplasm not otherwise specified (HCN NOS) will also be eligible.
* Disease Status: Participants must have measurable disease by RECIST criteria, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) measured at ≥20 mm with conventional technique or ≥10 mm with spiral CT scan, MRI, or calipers by clinical exam. See Section 10 for the evaluation of measurable disease.
* Performance Level: Karnofsky performance status ≥ 60% for patients ≥ 16 years of age or Lansky ≥ 60% for patients \< 16 years of age.
* Prior Therapy: Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy.
* Patients must not have received standard or targeted treatment regimens within 14 days of initiation of treatment with pembrolizumab.
* Patients must not have received prior radiotherapy within 7 days of initiation of treatment with pembrolizumab. Patients who have experienced radiation-induced adverse events must recover to a grade 1 prior to enrollment.
* Organ Function Requirements: Participants must have normal organ and marrow function as defined below:
* Adequate Bone Marrow Function defined as:
* Peripheral absolute neutrophil count (ANC) ≥ 750/μL
* Platelet count ≥ 75,000/μL (can be transfused)
* Adequate Liver Function defined as:
* Total bilirubin \< 1.5 x institutional upper limit of normal (ULN)
* AST(SGOT) ≤ 2.5 x ULN
* ALT(SGPT) ≤ 2.5 x ULN
* If liver function studies are more elevated than the thresholds above, and if if this elevation is felt secondary to tumor, patients may still be eligible for enrollment after discussion with the study PI.
* Adequate Renal and Metabolic Function defined as:
* A serum creatinine based on age/gender as follows:
* Age Maximum Serum Creatinine (mg/dL) Male Female
* 1 to \<2 years 0.6 0.6
* 2 to \<6 years 0.8 0.8
* 6 to \<10 years 1.0 1.0
* 10 to \<13 years 1.2 1.2
* 13 to \<16 years 1.5 1.4
* \>16 years 1.7 1.4
* OR
* Creatinine clearance ≥60 mL/min/1.73 m2 for participants with creatinine levels above institutional normal.
* Amylase ≤ 1.5 x ULN
* Lipase ≤ 1.5 x ULN
* If liver function studies are more elevated than the thresholds above, and if this elevation is felt secondary to tumor, patients may still be eligible for enrollment after discussion with the study PI.
\-- Adequate Thyroid Function defined as:
\--- TSH ≤1.5 ULN. Patients can be receiving thyroid supplementation.
* Confirmation of Insurance Pre-authorization approval for Pembrolizumab.
* Patients, their parent, and/or legally authorized representative must be able to understand and be willing to sign a written informed consent document. Assent for participants \< 18 years will follow institutional guidelines. The protocol will require approval by each institution's Institutional Review Board.
* The effects of pembrolizumab on the developing human fetus are unknown. For this reason, patients of child-bearing and child-fathering potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 4 months after completion of pembrolizumab administration. Should a female become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Males treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of pembrolizumab administration.
* Women of child bearing potential (WOCBP) must have a negative serum or urine pregnancy test within 24 hours of each treatment.
* A tumor sample must be available for submission to the central laboratory (Dana-Farber Cancer Institute, see Section 9). If surgery was performed at the time of recurrence, this sample, in addition to a diagnostic sample should be submitted. If no re-operation was performed, archived tissue from diagnosis or the most recent procedure should be submitted (see section 9 for further details regarding tissue specifications).
Exclusion Criteria:
* Participants who are receiving any other investigational agents are not eligible.
* Participants who have received checkpoint inhibitors (PD-1, PD-L1, and CTLA-4 inhibitors) are not eligible.
* Participants who have received antibody-based therapies are not eligible if they are within 3 half-lives of receipt of the last antibody dose.
* Participants who are receiving chronic steroids are not eligible.Chronic steroids are defined as either \> or = 2mg/kg/day of body weight or \> or = 20mg/day of prednisone or equivalent for persons who weigh \> or = 10kg administered for \> or = 14 consecutive days.
* Participants who are receiving anti-inflammatory or immunosuppressive medications are not eligible.
* Participants with known autoimmune disease, with the exceptions of childhood asthma or atopic dermatitis, are not eligible.
* Patients with a history of a positive test for human immunodeficiency virus or acquired immunodeficiency syndrome are not eligible.
* Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to pembrolizumab are not eligible. History of severe allergy to monoclonal antibody therapies (i.e. anaphylaxis) are likewise an exclusion.
* Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, or psychiatric illness/social situations that would limit compliance with study requirements are not eligible.
* Patients with prior solid organ transplantation are not eligible. DRUG: Pembrolizumab
Hepatocellular Carcinoma, Childhood, Fibrolamellar Carcinoma, Liver Cancer, Liver Cancer, Pediatric
Hepatocellular Carcinoma Childhood, Fibrolamellar Carcinoma, Liver Cancer, Liver Cancer Pediatric
A Study to Compare Standard Chemotherapy to Therapy With CPX-351 and/or Gilteritinib for Patients With Newly Diagnosed AML With or Without FLT3 Mutations
- cancer@cchmc.org
ALL
6 months to 21 years old
PHASE3
NCT04293562
Inclusion Criteria:
* All patients must be enrolled on APEC14B1 and consented to Eligibility Screening (Part A) prior to enrollment and treatment on AAML1831. Bone marrow and/or blood must have been submitted to the BPC via APEC14B1 for testing of FLT3 markers. Patients without samples submitted for FLT3 testing are not eligible
* Patients must be at least 6 months of age and less than 22 years of age at the time of study enrollment
* Patient must be newly diagnosed with de novo AML according to the 2016 World Health Organization (WHO) classification with or without extramedullary disease
* Patient must have 1 of the following:
* \>= 20% bone marrow blasts (obtained within 14 days prior to enrollment)
* In cases where extensive fibrosis may result in a dry tap, blast count can be obtained from touch imprints or estimated from an adequate bone marrow core biopsy
* \< 20% bone marrow blasts with one or more of the genetic abnormalities associated with childhood/young adult AML as provided in the protocol (sample obtained within 14 days prior to enrollment)
* A complete blood count (CBC) documenting the presence of at least 1,000/uL (i.e., a white blood cell \[WBC\] count \>= 10,000/uL with \>= 10% blasts or a WBC count of \>= 5,000/uL with \>= 20% blasts) circulating leukemic cells (blasts) if a bone marrow aspirate or biopsy is pending or cannot be performed (performed within 7 days prior to enrollment)
* ARM C: Patient must be \>= 2 years of age at the time of Late Callback
* ARM C: Patient must have FLT3/ITD allelic ratio \> 0.1 as reported by Molecular Oncology
* ARM C: Patient does not have any congenital long QT syndrome or congenital heart block
* ARM C: Females of reproductive potential must agree to use effective contraception during treatment and for at least 6 months after the last dose of gilteritinib
* ARM C: Lactating women must agree not to breastfeed during treatment with gilteritinib and for 2 months after the last dose of gilteritinib
* ARM C: Males of reproductive potential must agree to use effective contraception during treatment and for at least 4 months after the last dose of gilteritinib
* ARM D: Patient must be \>= 2 years of age at the time of Late Callback
* ARM D: Patient must have one of the clinically relevant non-ITD FLT3 activating mutations as reported by Foundation Medicine
* ARM D: Females of reproductive potential must agree to use effective contraception during treatment and for at least 6 months after the last dose of gilteritinib
* ARM D: Lactating women must agree not to breastfeed during treatment with gilteritinib and for 2 months after the last dose of gilteritinib
* ARM D: Males of reproductive potential must agree to use effective contraception during treatment and for at least 4 months after the last dose of gilteritinib
* NEUROPSYCHOLOGICAL TESTING: Patient must be enrolled on Arm A or Arm B. Patients who transfer to Arm C or Arm D are not eligible
* NEUROPSYCHOLOGICAL TESTING: Patient must be 5 years or older at the time of enrollment
* NEUROPSYCHOLOGICAL TESTING: English-, French- or Spanish-speaking
* NEUROPSYCHOLOGICAL TESTING: No known history of neurodevelopmental disorder prior to diagnosis of AML (e.g., Down syndrome, fragile X, William syndrome, mental retardation)
* NEUROPSYCHOLOGICAL TESTING: No significant visual or motor impairment that would prevent computer use or recognition of visual test stimuli
* All patients and/or their parents or legal guardians must sign a written informed consent
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Exclusion Criteria:
* Fanconi anemia
* Shwachman Diamond syndrome
* Patients with constitutional trisomy 21 or with constitutional mosaicism of trisomy 21
* Telomere disorders
* Germline predispositions known, or suspected by the treating physician to increase risk of toxicity with AML therapy
* Any concurrent malignancy
* Juvenile myelomonocytic leukemia (JMML)
* Philadelphia chromosome positive AML
* Mixed phenotype acute leukemia
* Acute promyelocytic leukemia
* Acute myeloid leukemia arising from myelodysplasia
* Therapy-related myeloid neoplasms
* Patients with persistent cardiac dysfunction prior to enrollment, defined as ejection fraction (EF) \< 50% (preferred method Biplane Simpson's EF) or if EF unavailable, shortening fraction (SF) \< 24%. \*Note: if clinically safe and feasible, repeat echocardiogram is strongly advised in order to confirm cardiac dysfunction following clinical stabilization, particularly if occurring in the setting of sepsis or other transient physiologic stressor. If the repeat echocardiogram demonstrates an EF \>= 50%, the patient is eligible to enroll and may receive an anthracycline-containing Induction regimen
* Administration of prior anti-cancer therapy except as outlined below:
* Hydroxyurea
* All-trans retinoic acid (ATRA)
* Corticosteroids (any route)
* Intrathecal therapy given at diagnosis
* In particular, strong inducers of CYP3A4 and/or P-glycoprotein (P-gp) should be avoided from the time of enrollment until it is determined whether the patient will receive gilteritinib. Patients receiving gilteritinib will be required to avoid strong CYP3A4 inducers and/or strong P-gp inducers for the duration of the study treatment
* Patients \< 8.3 kg at study enrollment are not eligible
* Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential
* Lactating females who plan to breastfeed their infants
* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation
* ARM D: Patient does not have any congenital long QT syndrome or congenital heart block PROCEDURE: Allogeneic Hematopoietic Stem Cell Transplantation, DRUG: Asparaginase Erwinia chrysanthemi, PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Marrow Aspiration, PROCEDURE: Bone Marrow Biopsy, PROCEDURE: Computed Tomography, DRUG: Cytarabine, DRUG: Daunorubicin Hydrochloride, DRUG: Dexrazoxane Hydrochloride, DRUG: Etoposide, OTHER: Fludeoxyglucose F-18, DRUG: Gemtuzumab Ozogamicin, DRUG: Gilteritinib Fumarate, DRUG: Liposome-encapsulated Daunorubicin-Cytarabine, PROCEDURE: Magnetic Resonance Imaging, DRUG: Methotrexate, DRUG: Mitoxantrone Hydrochloride, PROCEDURE: Positron Emission Tomography, OTHER: Questionnaire Administration, DRUG: Therapeutic Hydrocortisone
Acute Myeloid Leukemia
KiteLock 4% EDTA Lock Solution for the Prevention of Occlusions in Children With Intestinal Failure
Crystal Slaughter - crystal.slaughter@cchmc.org
ALL
4 weeks to 18 years old
NA
NCT05879835
Inclusion Criteria:
• Patients managed by the intestinal rehabilitation program at one of the participating centers.
• Diagnosis of intestinal failure defined as need for PN support for \>60 days in previous 74 days for primary intestinal disease (short bowel syndrome, primary motility disorder, mucosal enteropathy).
• Expectation of the treating physician that the patient will require PN for at least 6 months following enrollment.
• Age less than 18 years at diagnosis but greater than 4 weeks chronological age or 40 weeks estimated gestational age, whichever is greater.
• Stable TPN cycling (4 hours off TPN minimum per day) enabling home TPN management
• Presence of a tunneled central venous catheter (CVC), port-a-catheter, or peripherally inserted central catheter (PICC).
• Clinical stability for at least 4 weeks and no acute medical comorbidities.
• A minimum dwell time of 4 consecutive hours daily.
• Care provider willing to provide informed consent to participate in the trial and willing to comply with randomization and study protocol.
Exclusion Criteria:
• A temporary CVC (jugular or femoral) or peripheral catheter.
• Patients receiving long-term PN, but not due to a primary intestinal disorder (i.e., oncology patients or premature neonates on PN due to intestinal immaturity).
• Known hypersensitivity, allergy, or reaction to EDTA.
• Pregnancy or nursing mother.
• Participation in another investigational device or drug trial within 30 days prior to enrollment (unless approved by the principal investigators of the trial).
• Severe coagulopathy (platelets \<50,000, or INR \> 1.5).
• Diagnosis of immunodeficiency disorder.
• Unstable medical condition requiring hospital admission
• Received antibiotic therapy for CLABSI within last 14 days.
DEVICE: KiteLock 4% Sterile Catheter Lock Solution, DEVICE: Heparin Lock Solution
Pediatric Intestinal Failure
catheter lock solution, pediatric intestinal failure, intestinal failure, central venous catheter, KiteLock 4%, heparin, total parenteral nutrition, parenteral nutrition
A Study of Axatilimab at 3 Different Doses in Participants With Chronic Graft Versus Host Disease (cGVHD) (AGAVE-201)
Sara Loveless - sara.loveless@cchmc.org
ALL
2 years and over
PHASE2
NCT04710576
Inclusion Criteria:
• Participants must be 2 years of age or older, at the time of signing the informed consent.
• Participants who are allogeneic hematopoietic stem cell transplantation (HSCT) recipients with active cGVHD requiring systemic immune suppression. Active cGVHD is defined as the presence of signs and symptoms of cGVHD per 2014 NIH Consensus Development Project on Criteria for Clinical trials in cGVHD.
• Participants with refractory or recurrent active cGVHD despite at least 2 lines of systemic therapy. * Refractory disease defined as meeting any of the following criteria: * The development of 1 or more new sites of disease while being treated for cGVHD. * Progression of existing sites of disease despite at least 1 month of standard or investigation therapy for cGVHD. * Participants who have not achieved a response within 3 months on their prior therapy for cGVHD and for whom the treating physician believes a new systemic therapy is required. * Recurrent cGVHD is active, symptomatic disease (after an initial response to prior therapy) as defined, based on the NIH 2014 consensus criteria, by organ-specific or global assessment or for which the physician believes that a new line of systemic therapy is required.
• Participants may have persistent, active acute and cGVHD manifestations (overlap syndrome), as defined by 2014 NIH Consensus Development Project on Criteria for Clinical trials in cGVHD.
• Karnofsky Performance Scale of ≥60 (if aged 16 years or older); Lansky Performance Score of ≥60 (if aged \<16 years)
• Adequate organ and bone marrow functions evaluated during the 14 days prior to randomization.
• Creatinine clearance (CrCl) ≥30 milliliter/minute based on the Cockcroft-Gault formula in adult participants and Schwartz formula in pediatric participants.
• Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Concomitant use a of systemic corticosteroid is allowed but not required. Topical and inhaled corticosteroid agents are allowed. If a participant is taking corticosteroids at study randomization, they must be on a stable dose of corticosteroids for at least 2 weeks prior to Cycle 1 Day 1.
• Concomitant use of CNI or mammalian target of repamycin (mTOR) inhibitors (sirolimus or everolimus) is allowed but not required.
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and protocol. A parent/guardian should provide consent for pediatric participants unable to provide consent themselves; in addition, where applicable pediatric participants should sign their own assent form.
Exclusion Criteria:
Participants are excluded from the study if any of the following criteria apply:
• Has acute GVHD without manifestations of cGVHD.
• Any evidence (histologic, cytogenetic, molecular, hematologic, or mixed) of relapse of the underlying cancer or post-transplant lymphoproliferative disease at the time of screening.
• History of acute or chronic pancreatitis.
• History of myositis.
• History or other evidence of severe illness, uncontrolled infection or any other conditions that would make the participant, in the opinion of the Investigator, unsuitable for the study.
• Participants with acquired immune deficiency syndrome (AIDS).
• Hepatitis B (defined as hepatitis B virus \[HBV\] surface antigen positive and HBV core antibody positive, with positive HBV deoxyribonucleic acid \[DNA\], or HBV positive core antibody alone with positive HBV DNA. Hepatitis C (defined as positive hepatitis C \[HCV\] antibody with positive HCV ribonucleic acid \[RNA\]).
• Diagnosed with another malignancy (other than malignancy for which transplant was performed) within 3 years of randomization, unless previously treated with curative intent and approved by Sponsor's Medical Monitor (for example, completely resected basal cell or squamous cell carcinoma of the skin, resected in situ cervical malignancy, resected breast ductal carcinoma in situ, or low-risk prostate cancer after curative resection).
• Female participant who is pregnant or breastfeeding.
• Previous exposure to CSF1-R targeted therapies.
• Taking agents for treatment of cGVHD other than corticosteroids or either a CNI or mTOR inhibitor is prohibited.
• For approved or commonly used agents, other than corticosteroids, CNI and mTOR inhibitor, a washout of 2 weeks or 5 half-lives, whichever is shorter, is required at study enrollment.
• Receiving another investigational treatment within 28 days of randomization.
• Participants should not be participating in any other interventional study. Pediatric participants are encouraged to also participate in the ongoing developmental studies of the Pediatric cGVHD Symptom Scale (PCSS).
DRUG: Axatilimab
Chronic Graft-versus-host-disease
cGVHD, AGAVE-201, GVHD, graft versus host disease, graft-versus-host-disease
Pediatric Pulmonary Hypertension Network (PPHNet) Informatics Registry (PPHNet)
Sarah Speed - sarah.speed@cchmc.org
ALL
1 day to 21 years old
NCT02249923
Inclusion Criteria:
* The subject's age of onset of pulmonary hypertension must be prior to age 18 years
* The person providing consent must be able to read either Spanish or English.
* The subject (and/or parent/legal guardian) must be able to provide informed consent
Exclusion Criteria:
* Diagnosed with pulmonary hypertension after age 18
* Refusal to sign informed consent Pulmonary Vascular Disease, Pulmonary Arterial Hypertension
Pulmonary Arterial Hypertension (PAH), Pulmonary Vascular Disease (PVD), Registry, Pediatric
Evaluation of Analgesia for Spine Fusion Elective Surgery in Children (PRECISE)
Geisler - Kristie.Geisler@cchmc.org
ALL
10 years to 18 years old
PHASE3
NCT06626503
Inclusion Criteria:
• Age 10 - \< 18 years
• American Society of Anesthesiologists (ASA) Physical Status 1 or 2
• Undergoing PSF for idiopathic scoliosis
• Participant or legal guardian can speak and read English or Spanish
Exclusion Criteria:
• Pregnant patients
• Methadone allergy
• Preoperative prolonged QTc more than 460 msec (-30 days to 0 day)
• Subjects undergoing concomitant treatment with known cytochrome P450 inhibitors included in methadone labeling (i.e. macrolides (e.g. erythromycin), azole-antifungal agents (e.g. ketoconazole, voriconazole), protease inhibitors (e.g. ritonavir), fluconazole, SSRIs (e.g. sertraline, fluvoxamine)
• Preoperative opioid use within 30 days before surgery
• History of severe sleep apnea, defined as a prior sleep study demonstrating an apnea-hypopnea index (AHI) greater than 10.
• Significant liver, kidney, neurological disease, developmental delay, or any other co-existing medical condition per discretion of the clinical investigator
DRUG: Methadone based ERAS, DRUG: Non-methadone based group
Idiopathic Scoliosis
A Study to Evaluate the Safety, Efficacy, PK, PD and Immunogenicity of Cipaglucosidase Alfa/Miglustat in IOPD Subjects Aged 0 to <18 (ROSSELLA)
Laurie Bailey - laurie.bailey@cchmc.org
ALL
Up to 17 years old
PHASE3
NCT04808505
Inclusion Criteria:
Cohort 1:
• Male or female subjects who are aged 6 months to \< 18 years on Day 1
• Subject must have documentation of IOPD genotype
• Subject must have had hypertrophic cardiomyopathy at the time of diagnosis
• Subject must have received ERT for at least 6 months immediately before enrollment. For subjects whose ERT dosage has been modified, the subject must have been on the modified dosage and regimen for at least 3 months before enrollment
• Subjects aged ≥ 12 to \< 18 years must perform one valid 6-minute walk test (6MWT) (≥ 75 meters) at screening; Subjects aged ≥ 5 to \< 12 years must perform one valid 6MWT (≥ 40 meters) at screening; Subjects aged 18 months to \< 5 years must be ambulatory and assessed to be likely to be able to perform 6MWT (≥ 40 meters) when they turn 5 years old
• Subjects must have experienced a clinical decline on their current rhGAA dose and frequency Cohort 2:
• Male or female subjects who are aged 0 to \<6 months at Day 1
• Subject must have documentation of IOPD genotype
• Subject must have had hypertrophic cardiomyopathy at the time of diagnosis
• Subject is ERT-naïve Long-term Extension (Cohort 1 or Cohort 2): 1\. Subject must have, in the opinion of the investigator, benefited from therapy with cipaglucosidase alfa/miglustat during the 104-week primary treatment period with no significant safety concerns.
Exclusion Criteria:
Cohort 1 and Cohort 2, unless specified
• Subject requires invasive ventilation (eg, tracheostomy)
• Subject is CRIM negative and has not received prophylactic immunomodulation (Cohort 1); Subject is CRIM negative and will not be receiving prophylactic immunomodulation (Cohort 2)
• Subject has a history of life-threatening IARs/hypersensitivity (eg, anaphylaxis and severe cutaneous reactions) to ERT (eg, alglucosidase alfa, cipaglucosidase alfa, miglustat) or other iminosugars, or to any of the excipients, where rechallenge was unsuccessful
• Subject has prior history of illness or condition known to affect motor function
• Female subject is pregnant (or intends to get pregnant) or breastfeeding at screening (Cohort 1)
BIOLOGICAL: Cipaglucosidase alfa, DRUG: Miglustat
Glycogen Storage Disease Type II Infantile Onset
Motor Training for Infants With Cerebral Palsy
Karen L Harpster, PhD, OTR/L - karen.harpster@cchmc.org
ALL
3 months to 8 months old
NA
NCT04886895
Inclusion Criteria:
* Age at enrollment: between 3-8 months corrected age
* Caregivers fluent in English
* Preterm infants with objectively defined severe diffuse white matter abnormality on MRI at term OR
* High-risk infants (e.g., preterm, neonatal hypoxic-ischemic encephalopathy, perinatal stroke) with moderate-severe injury on structural MRI or cranial ultrasound (e.g., basal ganglia/thalamic signal intensity, cystic periventricular leukomalacia, encephalomalacia, large stroke, and/or severe intraventricular/periventricular hemorrhage) at around term-equivalent age or before Neonatal Intensive Care Unit discharge AND either:
* "Absent" fidgety movements based on the Prechtl General Movement Assessment (GMA) between 3-4 months corrected age OR
* A score of 56 or below on the Hammersmith Infant Neuromotor Examination (HINE) between 3-6 months corrected age (31)
Exclusion Criteria:
* Medical conditions that restrict active participation such as oxygen dependence
* Infants with significant visual deficits defined by the inability to track an object horizontally
* Living in a remote location prohibiting drives to the hospital every other week. OTHER: Let's Move Motor Intervention
Cerebral Palsy
motor skills, occupational therapy, physical therapy
A-LiNK: Improving Outcomes in Autoimmune Liver Disease (ALINK)
Cyd M Castro-Rojas, PhD - Cyd.CastroRojas@cchmc.org
ALL
NCT05750498
Inclusion Criteria:
* Clinical diagnosis of autoimmune hepatitis (AIH)
* Clinical diagnosis of primary sclerosing cholangitis (PSC)
* Clinical diagnosis of autoimmune sclerosing cholangitis (ASC)
Exclusion Criteria:
• History of liver transplant OTHER: No interventions
Autoimmune Hepatitis, Primary Sclerosing Cholangitis
Pediatrics, Autoimmune Hepatitis, Primary Sclerosing Cholangitis, Autoimmune Sclerosing Cholangitis, Chronic Liver Disease, End-stage Liver Disease, Clinical Registry, Research Registry, Quality Improvement, Outcomes Research, Comparative Effectiveness Research, Patient Reported Outcomes, Health Services Research
A Study About How Blood Cell Growth Patterns Relate to Heart Health After Treatment for Hodgkin Lymphoma
- cancer@cchmc.org
ALL
7 years and over
NCT05705531
Inclusion Criteria:
* Patient must be \>= 7 years of age at the time of enrollment (age to perform an MRI without sedation).
* History of pathologically confirmed classical Hodgkin Lymphoma (cHL) initially diagnosed when the patient was \>= 2 and \< 22 years of age.
* As part of frontline therapy for cHL, the patient must have received a cumulative doxorubicin equivalent anthracycline dose of ≥ 200 mg/m\^2 as estimated in doxorubicin isotoxic equivalents dose conversion calculation.
* Note: History of COG therapeutic trial participation is not required. Institutional records (e.g., clinic note, treatment summary, chemotherapy roadmap) can be used as reference documentation of receipt of anthracycline dose.
* All systemic cancer treatment must have been completed ≥ 2 years prior to study enrollment.
* Not known to have had a primary event (relapse/second malignancy/death).
* Note: Subjects treated at another institution are eligible if they are now being followed at the current COG institution, if the study procedures can be performed and the data accessible by a COG institution where the study is open.
* Patient must have access to cardiac MRI at the enrolling institution and must be able to complete cardiac MRI without sedation.
Exclusion Criteria:
* Medical contraindication to undergoing a non-contrast cardiac MRI.
* Patients with nodular lymphocyte-predominant HL.
* Received cancer therapy in addition to that for primary Hodgkin Disease (e.g., for disease progression or recurrence, or subsequent malignant neoplasm).
* History of CTCAE grade 3 or higher cardiovascular disease or condition known to exist prior to the patient's initial diagnosis of cHL.
* Note: exceptions are made for congenital conditions considered fully resolved by surgery and chronic conditions such as hypertension or hypercholesterolemia that are managed with medical intervention.
* History of an immunodeficiency that existed prior to cHL diagnosis, such as primary immunodeficiency syndromes, organ transplant recipients and conditions requiring systemic immunosuppressive agents. PROCEDURE: Archive Sample Retrieval, PROCEDURE: Biospecimen Collection, OTHER: Electronic Health Record Review, PROCEDURE: Magnetic Resonance Imaging, OTHER: Survey Administration
Cardiovascular Disorder, Classic Hodgkin Lymphoma, Clonal Hematopoiesis
TRANSPIRE: Lung Injury in a Longitudinal Cohort of Pediatric HSCT Patients
Sara Loveless - sara.loveless@cchmc.org
ALL
Up to 24 years old
NCT04098445
Inclusion Criteria:
* Subjects ≤ 24 years of age undergoing allogeneic or autologous HSCT.
Exclusion Criteria:
* Subjects over 24 years of age. Hematopoietic Stem Cell Transplant (HSCT), Diffuse Alveolar Hemorrhage, Thrombotic Microangiopathies, Interstitial Pneumonitis, Bronchiolitis Obliterans