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A Study of a New Way to Treat Children and Young Adults With a Brain Tumor Called NGGCT
- cancer@cchmc.org
ALL
3 years to 29 years old
PHASE2
NCT04684368
Inclusion Criteria:
* Patients must be \>= 3 years and \< 30 years at the time of study enrollment
* Patients must be newly diagnosed with localized primary CNS NGGCT of the suprasellar and/or pineal region by pathology and/or serum or cerebrospinal fluid (CSF) elevation of AFP above institutional normal or \> 10 ng/mL or human chorionic gonadotropin (hCG) beta \> 100 mIU/mL as confirmed by Rapid Central Marker Screening Review on APEC14B1-CNS. Suprasellar, pineal and bifocal tumors are included. (CSF tumor markers and cytology must be within 31 days prior to enrollment and start of protocol therapy \[repeat if necessary\]. Serum tumor markers, AFP and hCGbeta must be within 7 days prior to enrollment and start of protocol therapy \[repeat if necessary\]). Basal ganglia or other primary sites are excluded
* Patients with any of the following pathological elements are eligible: endodermal sinus (yolk sac), embryonal carcinoma, choriocarcinoma, malignant/immature teratoma and mixed germ cell tumor (GCT) (i.e., may include some pure germinoma) if malignant elements listed above are present. Patients with only mature teratoma are excluded. Patients with pure germinoma admixed with mature teratoma are excluded (would be eligible for pure germinoma protocols)
* Patients must have a cranial MRI with and without gadolinium at diagnosis/prior to enrollment. If surgical resection is performed, patients must have pre-operative and post operative brain MRI with and without gadolinium. The post operative brain MRI should be obtained within 72 hours of surgery. If patient has a biopsy only, post-operative brain MRI is recommended but not required (within 31 days prior to study enrollment and start of protocol therapy )
* Patients must have a spine MRI with gadolinium obtained at diagnosis/prior to enrollment. Spine MRI with and without gadolinium is recommended (within 31 days prior to study enrollment and start of protocol therapy)
* Lumbar CSF must be obtained prior to study enrollment unless medically contraindicated. If a patient undergoes surgery and lumbar CSF cytology cannot be obtained at the time of surgery, then it should be performed at least 10 days following surgery and prior to study enrollment. False positive cytology can occur within 10 days of surgery
* Patients must have RAPID CENTRAL TUMOR MARKER REVIEW CSF tumor markers obtained prior to enrollment unless medically contraindicated. Ventricular CSF obtained at the time of CSF diversion procedure (if performed) is acceptable for tumor markers but lumbar CSF is preferred. In case CSF diversion and biopsy/surgery are combined, CSF tumor markers should be collected first
* Peripheral absolute neutrophil count (ANC) \>= 1000/uL (within 7 days prior to enrollment)
* Platelet count \>= 100,000/uL (transfusion independent) (within 7 days prior to enrollment)
* Hemoglobin \>= 8.0 g/dL (may receive red blood cell \[RBC\] transfusions) (within 7 days prior to enrollment)
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 or a serum creatinine based on age/gender as follows (within 7 days prior to enrollment):
* Age: Maximum serum creatinine (mg/dL)
* 3 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: male (1.7), 1.4 (female)
* Total bilirubin =\< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment)
* Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 135 U/L (within 7 days prior to enrollment)
* Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L
* Central nervous system function defined as:
* Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled
* Patients must not be in status epilepticus, coma or assisted ventilation prior to study enrollment
* Protocol therapy must begin within 31 calendar days of definitive surgery or clinical diagnosis, whichever is later. If a biopsy only was performed, the biopsy date will be considered the date of definitive surgery. For patients who have a biopsy or incomplete resection at diagnosis followed by additional surgery, the date of the last resection will be considered the date of definitive surgery.
* 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
* NEUROCOGNITIVE FUNCTION AND QUALITY OF LIFE ASSESSMENT:
* English-, Spanish-, or French- speaking
* Note: Patients who speak a language other than English, Spanish, or French will be allowed to participate in ACNS2021 but will not complete the neurocognitive and quality of life assessments
* No known history of neurodevelopmental disorder prior to diagnosis of NGGCT (e.g., Down syndrome, fragile X, William syndrome, intellectual disability). Patients with NF1 will be allowed to participate
* Additional eligibility criteria for the COG Standardized Neuropsychological Battery only: must be at a site that has a psychologist to administer the battery
* Note: If not eligible for the COG Standardized Battery, patients should still complete the Behavior Rating Inventory of Executive Function, Second Edition (BRIEF-2), Pediatric Quality of Life Inventory (PedsQL), Adaptive Behavior Assessment System Third Edition (ABAS-3), and Behavior Assessment System for Children, Third Edition (BASC-3) questionnaires
Exclusion Criteria:
* Patients with tumors located outside the ventricles (i.e., basal ganglia, thalamus)
* Patients with only mature teratoma and non-elevated markers upon tumor sampling at diagnosis
* Patients who have received any prior tumor-directed therapy for their diagnosis of NGGCT other than surgical intervention and corticosteroids
* Patients with metastatic disease (i.e., MRI evaluation, lumbar CSF cytology or intraoperative evidence of dissemination)
* Female patients who are pregnant, since fetal toxicities and teratogenic effects have been noted for several of the study drugs
* Note: Serum and urine pregnancy tests may be falsely positive due to HCGbeta-secreting germ cell tumors. Ensure the patient is not pregnant by institutional standards
* 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 PROCEDURE: Biospecimen Collection, DRUG: Carboplatin, DRUG: Etoposide, BIOLOGICAL: Filgrastim, DRUG: Ifosfamide, PROCEDURE: Magnetic Resonance Imaging, DRUG: Mesna, BIOLOGICAL: Pegfilgrastim, PROCEDURE: Peripheral Blood Stem Cell Transplantation, OTHER: Questionnaire Administration, RADIATION: Radiation Therapy, RADIATION: Radiation Therapy, PROCEDURE: Second-Look Surgery, DRUG: Thiotepa
Central Nervous System Nongerminomatous Germ Cell Tumor, Choriocarcinoma, Embryonal Carcinoma, Immature Teratoma, Malignant Teratoma, Mixed Germ Cell Tumor, Pineal Region Germ Cell Tumor, Pineal Region Immature Teratoma, Pineal Region Yolk Sac Tumor, Suprasellar Germ Cell Tumor
Study of Inotuzumab Ozogamicin, Venetoclax, and Dexamethasone for Relapsed B-cell ALL
- jeremy.rubinstein@cchmc.org
ALL
1 year to 39 years old
PHASE1
NCT06863259
Inclusion Criteria:
Diagnosis:
\- Patients must have relapsed B-ALL \> 5 % bone marrow blasts with or without extramedullary disease.
* At least 20% of leukemic blasts must demonstrate surface expression of CD22 at the time of relapse by flow cytometry of a bone marrow aspirate. In the case of an inadequate aspirate sample (dry tap) or if bone marrow aspirate is unable to be obtained due to patient clinical status, then flow cytometry of peripheral blood specimens may be substituted if the patient has \> 1,000/µL circulating blasts. Alternatively, CD22 expression may be documented by immunohistochemistry of a relapse bone marrow biopsy specimen.
* Patients with one of the following:
* 2nd or greater relapse OR first relapse less than 24 months from diagnosis OR first or greater relapse in patients over 18.
* Primary refractory disease: defined as \> 1% bone marrow blasts by flow MRD after at least 2 courses of frontline chemotherapy. Patients who receive 2 courses of chemotherapy and 1 course of blinatumomab are also eligible, but no further treatment attempts beyond that are permitted.
* Any relapse after HSCT or CAR-T therapy.
* Patients with Ph+ ALL must have had at least two prior therapy attempts and failed all available tyrosine kinase inhibitors.
Prior Therapy:
\- Cytotoxic chemotherapy:
• At least 14 days must have elapsed from the completion of systemic cytotoxic therapy that is known to be myelosuppressive with the exception of hydroxyurea for cytoreduction OR conventional maintenance chemotherapy (i.e., corticosteroids, vincristine, 6MP, and/or oral methotrexate) for patient who relapse while on maintenance therapy OR lumbar puncture with intrathecal chemotherapy. Corticosteroids, vincristine, 6MP, and/or oral methotrexate must be discontinued at least 24 hours prior to the start of protocol therapy. If corticosteroids were used to modify immune adverse events of prior therapy rather than as chemotherapy, at least 14 days must have elapsed since the last dose.
Systemic corticosteroids may be administered for cytoreduction up to 24 hours prior to the start of protocol therapy. For all patients, corticosteroids may be administered as a premedication for inotuzumab ozogamicin and as treatment for allergic reactions or for physiologic replacement/stress dosing of hydrocortisone for documented adrenal insufficiency.
At least seven days must have elapsed from the administration of anti-cancer agents not known to be myelosuppressive.
* Anti-cancer agents that are antibodies
• At least 21 days must have elapsed from infusion of last dose of antibody. There is an exception for blinatumomab infusions, for which patients must have been off for at least 3 days.
* Radiation therapy
• At least 14 days must have elapsed since local palliative radiotherapy. At least 3 months must have elapsed if patient received cranial or craniospinal radiotherapy, if more than 50% of the pelvis was irradiated, or if total body irradiation was received. If other substantial bone marrow irradiation was given, at least 6 weeks must have elapsed.
* Hematopoietic stem cell transplant
• At least 90 days must have elapsed since stem cell transplant and at least 30 days from donor lymphocyte infusion. Patients must have had no more than one previous HSCT and currently have no evidence of active graft vs. host disease and must be off all immunosuppressive medications for at least 28 days.
* Chimeric antigen receptor T-cell therapy
• At least 30 days must have elapsed from the last CAR-T cell infusion. Patients may have previously received CD19 or CD22 directed CAR-T cell therapy but must still have CD22 expression on at least 20% of leukemic blasts.
* Prior Inotuzumab ozogamicin Patients with prior InO exposure must have received no more than 2.1 mg/m2 of prior InO and be at least 90 days from last dose.
* Prior Venetoclax exposure • Patients with prior venetoclax exposure are eligible provided they are at least 30 days from last dose.
Age:
\- Patients must be ≥ 1 year and ≤ 39.99 years of age at enrollment.
Performance status:
\- Karnofsky ≥ 50% for patients \> 16 years of age and 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.
Organ function requirements:
* Adequate Renal Function Defined As:
• An estimated GFR of 50 mL/min/1.73m2 as determined by the Levey formula (see appendix C), cystatin C, or radioisotope determination.
* Adequate Liver Function Defined As:
* Direct bilirubin ≤ 1.5 x upper limit of normal (ULN) for age.
* SGPT (ALT) \< 2.5 x the age-appropriate upper limit of normal (ULN) per local lab (unless elevation is related to leukemia involvement).
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
Exclusion Criteria:
* Patients with any prior history of SOS irrespective of severity.
* Patients with isolated CNS, testicular, or any other isolated extramedullary site of relapse.
* Patients with CNS3 disease at time of enrollment regardless of marrow involvement.
Concomitant Medications:
* Investigational drugs: patients who are currently receiving another investigational drug.
* Anti-cancer agents: Patients who are currently receiving or plan to receive other anti-cancer agents (except hydroxyurea, which may be continued until 24 hours prior to start of protocol therapy, and intrathecal chemotherapy).
* Anti-GVHD or agents to prevent organ rejection post-transplant. Patients who are receiving cyclosporine, tacrolimus, or other agents to prevent either graft vs host disease post bone marrow transplant or organ rejection post-transplant are not eligible for this trial. At least 3 half-lives must have relapsed after the last dose of GVHD or anti-rejection medications.
* Patients \> 10 kg AND \> 24months may receive azole antifungals (See altered venetoclax dosing provided for patients on azoles).
Infection:
* Patients with known HIV, hepatitis B or C infections. Testing to prove negative status is not required for enrollment unless it is deemed necessary for usual medical care of the patient.
* Patients who have an active uncontrolled infection defined as:
* Positive bacterial blood culture within 48 hours of study enrollment.
* Fever above 38.2℃ within 48 hours of study enrollment with documented infection Fever that is determined to be due to tumor burden is allowed if patients have documented negative blood cultures for at least 48 hours prior to enrollment and no concurrent signs or symptoms of active infection or hemodynamic instability.
* A positive fungal culture within 30 days of study enrollment or active therapy for presumed invasive fungal infection.
* Patients may be receiving IV or oral antibiotics to complete a course of therapy for a prior documented infection as long as cultures have been negative for at least 48 hours and signs or symptoms of active infection have resolved. For patients with C. difficile diarrhea, at least 72 hours of antibacterial therapy must have elapsed, and stools must have normalized to baseline.
* Active viral or protozoal infection requiring IV treatment.
* Patients known to have one of the following concomitant genetic syndromes: Blood syndrome, ataxia-telangiectasia, Fanconi anemia, Kostmann syndrome, Shwachmann-Diamond syndrome, or any other known bone marrow failure syndrome.
Pregnancy and Breastfeeding:
* There have been no human studies of inotuzumab ozogamicin or venetoclax in pregnant women. Based on safety studies, both agents have the potential to impair human male and female fertility to adversely affect human embryo-fetal development. Women of childbearing potential should be advised to avoid becoming pregnant while receiving inotuzumab ozogamicin and venetoclax. There is no known information regarding the presence of inotuzumab ozogamicin or venetoclax in human milk, the effects on the breast-fed infant, or the effect on milk production. Women should not breast-feed during treatment with inotuzumab ozogamicin or venetoclax and for at least 2 months after the final dose. Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained within 7 days prior to enrollment.
* Female patients who are sexually active and of reproductive potential are not eligible unless they agree to use an effective contraceptive method for the duration of their study participation and for 8 months after the last dose of inotuzumab ozogamicin or venetoclax.
* Men with female partners of childbearing potential should use effective contraception during treatment with inotuzumab ozogamicin and venetoclax and for at least 5 months after the last dose of inotuzumab ozogamicin and venetoclax.
* Lactating females are not eligible unless they agree not to breastfeed their infants.
* Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> Grade 2) with the exception of alopecia.
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to venetoclax or inotuzumab ozogamicin. DRUG: Inotuzumab Ozogamicin, Venetoclax, and Dexamethasone
B-cell Acute Lymphoblastic Leukemia
Relapsed, B-ALL, B-cell Acute Lymphoblastic Leukemia
Neuroimaging Reveals Treatment-related Changes in DLD
Kristi Barnett - Kristi.Barnett@cchmc.org
ALL
48 months to 71 months old
NA
NCT05268341
Inclusion Criteria:
* ages 48-71 months
* average nonverbal intelligence quotient (IQ)
* enrolled in participating center
* typically developing (receptive and expressive language, social, articulation, other)
* DLD for expressive grammar
* typical oral motor function
* typical social/pragmatics skills
* average hearing thresholds
* monolingual and native Standard English speakers
* does not have any uncorrected vision challenges
Exclusion Criteria:
* receiving co-occurring speech-language or other intervention for communication
* not MRI safe
* special education placement of child based on ability or behavior BEHAVIORAL: My Sentence Builder
Developmental Language Disorder
Registry of Patients With a Diagnosis of Spinal Muscular Atrophy (SMA)
Emily Hunsaker - emily.hunsaker@cchmc.org
ALL
NCT04174157
Inclusion Criteria:
* Patients treated with OAV-101 with a genetically confirmed diagnosis of SMA regardless of the date of diagnosis.
* Appropriate consent/assent has been obtained for participation in the registry
Exclusion Criteria:
\- Currently enrolled in an interventional clinical trial involving an investigational medicinal product to treat SMA.
Note: Patients who are participating in a Compassionate Use Program (CUP) for OAV-101 (Zolgensma) such as a Managed Access Program (MAP), an Expanded Access Program (EAP), Single Patient Investigational New Drug (IND) (SPI) or Named Patient Program (NPP) are eligible to enroll in the registry regardless of the date of a genetic or clinical diagnosis of SMA. OTHER: Prospective observational registry, DRUG: Zolgensma
Spinal Muscular Atrophy (SMA)
Otoferlin Gene-mediated Hearing Loss Natural History Study
Elizabeth Dolgas - Elizabeth.Dolgas@cchmc.org
ALL
Up to 44 years old
NCT05572073
Inclusion Criteria:
• Clinical presentation of bilateral sensorineural hearing loss (SNHL), including auditory neuropathy (AN) / auditory neuropathy spectrum disorder (ANSD) phenotype or medical history of AN / ANSD phenotype earlier in life
• Mutation(s) in the otoferlin gene
• Able and willing to comply with all study requirements, as evidenced by successful completion of the informed consent (and assent, if applicable) process Additional Criteria for Inclusion in the Prospective Phase:
• Presence of OAE / CM and absent / abnormal ABRs in at least one ear (that does not have a cochlear implant) within 12 months prior to or at the Month 0 visit
Exclusion Criteria:
• Unwillingness or inability of the potential participant and/or legally authorized representative to comply with all protocol requirements
• Presence of cochlear nerve deficiency and/or cochlear nerve dysplasia Additional Criteria for Exclusion from the Prospective Phase:
• Presence of bilateral cochlear implants at the time of record review or planned within the next 6 months
• Presence of middle ear or auditory brainstem implant(s) at the time of record review or planned within the next 6 months
• Any condition that would not allow the potential participant to complete follow-up assessments during the course of the study and/or, in the opinion of the Investigator, makes the potential participant unsuitable for the study Note: Potential participants will not be excluded based on their sex, gender, race, or ethnicity
OTHER: Natural History Study
Sensorineural Hearing Loss, Bilateral
Otoferlin Gene, sensorineural hearing loss (SNHL), auditory neuropathy, auditory neuropathy spectrum disorder
Study of Olutasidenib and Temozolomide in HGG
Peter M de Blank, MD - Peter.deBlank@cchmc.org
ALL
12 years to 39 years old
PHASE2
NCT06161974
Criteria TarGeT-D study strata definitions
* Stratum A: Patients with localized, intracranial, non-pontine, and non-thalamic IDH 1 mutant Astrocytoma, CNS WHO Grade 3.
* Stratum B: Patients with localized, intracranial, non-pontine, and non-thalamic IDH 1 mutant Astrocytoma, CNS WHO Grade 4.
* Stratum C: Patients with IDH-1 mutant DIPG, primary thalamic and spinal cord IDH-1 mutant HGG.
• Inclusion criteria already met to enroll on TarGeT-SCR (central molecular and histopathologic screening) based on:
• 1) Age: patients must be ≥12 years and ≤39 years of age at the time of enrollment on TarGeT-SCR 1.2) Diagnosis: * Patients with a newly-diagnosed IDH1-mutant HGG including DIPG are eligible. All patients must have 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, and histopathology consistent with diffuse WHO Grade 2-4 glioma. * All other HGG must be WHO Grade 3 or 4.
• 3) Disease status: There are no disease status requirements for enrollment * Measurable disease is not required. Patients without measurable disease are eligible. * Primary spinal tumor: Patients with a primary spinal HGG are eligible. * Patient must not have metastatic disease.
• Inclusion criteria for assignment to TarGeT-D, for all strata:
• 1 Presence of at Least One Relevant Actionable Somatic Mutation in IDH1 Gene, Detailed Here: * R132H, R132C, R132S, R132G or R132L. * Patients whose tumors harbor other alterations in addition to IDH1 mutation will potentially be eligible following consensus recommendation by the international multidisciplinary molecular screening committee. * Patients with IDH2 mutations are not eligible. * Patients with oligodendroglioma, IDH-mutant and 1p/19q-codeleted are not eligible.
• 2 Weight: Patients must weigh ≥35 Kg (77 lbs) at the time of enrollment on TarGeT-D.
• 3 Performance Level: Karnofsky ≥ 50% for patients \> 16 years of age and 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.
• 4 Prior Therapy 2.4.1 Surgery, radiation, and/or dexamethasone are permissible. Temozolomide administered concurrently with radiotherapy is permissible. Prior administration of bevacizumab is allowed, given at least 42-day washout period is completed prior to beginning treatment on TarGeT-D. No other prior anticancer therapy for HGG will be allowed.
• 4.2 Radiation therapy requirements: RT, delivered via photon or proton beam, must have been administered at a standard dose including 54 Gy in 30 fractions for DIPG, 55-59.4 Gy in 30-33 fractions for other HGG or 45-54 Gy for primary spinal cord HGG. Any variances in the radiotherapy dose within 10% of the standard doses outlined above will be discussed with the Study Chair to confirm eligibility prior to study enrollment.
• 4.3 Timing between diagnosis and start of RT: Patients must have started RT \< 42 calendar days of initial diagnosis defined as the date of diagnostic biopsy or resection; if a patient underwent two upfront surgeries (e.g., biopsy then resection or debulking), this is the date of the second surgery. * Patients in pre-maintenance phase must enroll and start treatment no later than 21 calendar days post-completion of RT. * Patients not in pre-maintenance phase must enroll and start treatment no later than 35 calendar days post-completion of RT.
• 5 Organ Function Requirements 2.5.1 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). 2.5.2 Adequate Renal Function Defined as * Creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73 m2 OR * Maximum serum creatinine based on age/gender as follows: 10 to \< 13 yrs=1.2 mg/dL for males and females. 13 to \< 16 yrs=1.5 mg/dL for males and 1.4 mg/dL for females.
• 5.3 Adequate Liver Function Defined as: * Total bilirubin must be ≤ 1.5 × institutional ULN. * AST(SGOT)/ALT(SGPT) \< 3 × institutional ULN. * Alkaline Phosphatase \< 3 × institutional ULN. 2.5.4 Adequate Neurologic Function Defined as: * Patients with seizure disorder may be enrolled if well-controlled on anticonvulsants that are not a strong inducer or inhibitor of CYP3A4/5. * Patients must be able to swallow oral medications to be eligible for study enrollment.
• 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.
• Pregnancy or Breast-Feeding: Pregnant or breast-feeding women will not be entered on this study due to unknown potential risks of fetal and teratogenic adverse events as seen in animal studies. Pregnancy tests must be obtained in girls who are post-menarchal. Patients of childbearing or child fathering potential must agree to use 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 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.
• Using the following types of concomitant medications: * Corticosteroids: Patients receiving corticosteroids are eligible. The use of corticosteroids must be reported. * Investigational Drugs: Patients who are currently receiving another investigational drug are not eligible. * Anti-cancer Agents: Concurrent anti-cancer agents are not allowed with the exception of temozolomide given concurrently with RT and as protocol-instructed post RT maintenance therapy after enrollment on TarGeT-D. * Anticonvulsants: Patients who are receiving enzyme inducing anticonvulsants that are strong inducers of CYP3A4/5 are not eligible. * Strong CYP3A4/5 inducers: Patients who are receiving strong inducers of CYP3A4/5 are not eligible. Strong inducers of CYP3A4/5 should be avoided from 14 days prior to or 5 half-lives (whichever is longer) enrollment to the end of the study. * Patients who are receiving medications known to prolong QTc interval are not eligible * Selective serotonin reuptake inhibitors (SSRIs) such as citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac), fluvoxamine (Luvox), paroxetine (Paxil), sertraline (Zoloft) should be used with caution but are not contraindicated.
• Other Criteria * Infection: 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 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. * Patients with prior or ongoing clinically significant illness, medical or psychiatric condition, that, in the investigator's opinion, could affect the safety of the participant, or could impair the assessment of study results are not eligible. * Patients with any prior solid organ transplant are not eligible. * Patients with secondary/radiation-related HGG are not eligible. * Patients with metastatic/disseminated HGG who have received CSI 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 years and ≤39 years of age at the time of enrollment on TarGeT-SCR 1.2) Diagnosis: * Patients with a newly-diagnosed IDH1-mutant HGG including DIPG are eligible. All patients must have 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, and histopathology consistent with diffuse WHO Grade 2-4 glioma. * All other HGG must be WHO Grade 3 or 4.
• 3) Disease status: There are no disease status requirements for enrollment * Measurable disease is not required. Patients without measurable disease are eligible. * Primary spinal tumor: Patients with a primary spinal HGG are eligible. * Patient must not have metastatic disease.
• Inclusion criteria for assignment to TarGeT-D, for all strata:
• 1 Presence of at Least One Relevant Actionable Somatic Mutation in IDH1 Gene, Detailed Here: * R132H, R132C, R132S, R132G or R132L. * Patients whose tumors harbor other alterations in addition to IDH1 mutation will potentially be eligible following consensus recommendation by the international multidisciplinary molecular screening committee. * Patients with IDH2 mutations are not eligible. * Patients with oligodendroglioma, IDH-mutant and 1p/19q-codeleted are not eligible.
• 2 Weight: Patients must weigh ≥35 Kg (77 lbs) at the time of enrollment on TarGeT-D.
• 3 Performance Level: Karnofsky ≥ 50% for patients \> 16 years of age and 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.
• 4 Prior Therapy 2.4.1 Surgery, radiation, and/or dexamethasone are permissible. Temozolomide administered concurrently with radiotherapy is permissible. Prior administration of bevacizumab is allowed, given at least 42-day washout period is completed prior to beginning treatment on TarGeT-D. No other prior anticancer therapy for HGG will be allowed.
• 4.2 Radiation therapy requirements: RT, delivered via photon or proton beam, must have been administered at a standard dose including 54 Gy in 30 fractions for DIPG, 55-59.4 Gy in 30-33 fractions for other HGG or 45-54 Gy for primary spinal cord HGG. Any variances in the radiotherapy dose within 10% of the standard doses outlined above will be discussed with the Study Chair to confirm eligibility prior to study enrollment.
• 4.3 Timing between diagnosis and start of RT: Patients must have started RT \< 42 calendar days of initial diagnosis defined as the date of diagnostic biopsy or resection; if a patient underwent two upfront surgeries (e.g., biopsy then resection or debulking), this is the date of the second surgery. * Patients in pre-maintenance phase must enroll and start treatment no later than 21 calendar days post-completion of RT. * Patients not in pre-maintenance phase must enroll and start treatment no later than 35 calendar days post-completion of RT.
• 5 Organ Function Requirements 2.5.1 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). 2.5.2 Adequate Renal Function Defined as * Creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73 m2 OR * Maximum serum creatinine based on age/gender as follows: 10 to \< 13 yrs=1.2 mg/dL for males and females. 13 to \< 16 yrs=1.5 mg/dL for males and 1.4 mg/dL for females.
• 5.3 Adequate Liver Function Defined as: * Total bilirubin must be ≤ 1.5 × institutional ULN. * AST(SGOT)/ALT(SGPT) \< 3 × institutional ULN. * Alkaline Phosphatase \< 3 × institutional ULN. 2.5.4 Adequate Neurologic Function Defined as: * Patients with seizure disorder may be enrolled if well-controlled on anticonvulsants that are not a strong inducer or inhibitor of CYP3A4/5. * Patients must be able to swallow oral medications to be eligible for study enrollment.
• 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.
Exclusion Criteria:
• Pregnancy or Breast-Feeding: Pregnant or breast-feeding women will not be entered on this study due to unknown potential risks of fetal and teratogenic adverse events as seen in animal studies. Pregnancy tests must be obtained in girls who are post-menarchal. Patients of childbearing or child fathering potential must agree to use 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 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.
• Using the following types of concomitant medications: * Corticosteroids: Patients receiving corticosteroids are eligible. The use of corticosteroids must be reported. * Investigational Drugs: Patients who are currently receiving another investigational drug are not eligible. * Anti-cancer Agents: Concurrent anti-cancer agents are not allowed with the exception of temozolomide given concurrently with RT and as protocol-instructed post RT maintenance therapy after enrollment on TarGeT-D. * Anticonvulsants: Patients who are receiving enzyme inducing anticonvulsants that are strong inducers of CYP3A4/5 are not eligible. * Strong CYP3A4/5 inducers: Patients who are receiving strong inducers of CYP3A4/5 are not eligible. Strong inducers of CYP3A4/5 should be avoided from 14 days prior to or 5 half-lives (whichever is longer) enrollment to the end of the study. * Patients who are receiving medications known to prolong QTc interval are not eligible * Selective serotonin reuptake inhibitors (SSRIs) such as citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac), fluvoxamine (Luvox), paroxetine (Paxil), sertraline (Zoloft) should be used with caution but are not contraindicated.
• Other Criteria * Infection: 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 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. * Patients with prior or ongoing clinically significant illness, medical or psychiatric condition, that, in the investigator's opinion, could affect the safety of the participant, or could impair the assessment of study results are not eligible. * Patients with any prior solid organ transplant are not eligible. * Patients with secondary/radiation-related HGG are not eligible. * Patients with metastatic/disseminated HGG who have received CSI are not eligible.
DRUG: Olutasidenib + TMZ
High Grade Glioma, Astrocytoma, Astrocytoma, Grade III, Astrocytoma, Grade IV, Diffuse Intrinsic Pontine Glioma, WHO Grade III Glioma, WHO Grade IV Glioma, Metastatic Brain Tumor, Diffuse Midline Glioma, H3 K27M-Mutant, Thalamus Tumor, Spinal Tumor, IDH1 Mutation, IDH1 R132, IDH1 R132C, IDH1 R132H, IDH1 R132S, IDH1 R132G, IDH1 R132L, Oligodendroglioma
Verifying Antibodies After Live Immunization Delivery (VALID): A Study of Measles Vaccine Immunogenicity in Children With Sickle Cell Disease (VALID)
MacKenzie Tasset - macKenzie.tasset@cchmc.org
ALL
6 months to 6 years old
NCT07356050
Inclusion Criteria:
• Participants with confirmed Sickle Cell Disease.
• Participants 6 months and 6 years of age and due for measles vaccination within 3 months per national guidelines.
• Willing and able to provide informed consent
• Ability to comply with study related evaluations and follow-up visits.
Exclusion Criteria:
1\. Known primary immunodeficiency syndrome, cancer, or acquired immunodeficiency syndrome (AIDS) that would preclude vaccination with live virus vaccines. Sickle Cell Disease, Measles Vaccination, Sickle Cell Anemia
Measles Vaccine Immunogenicity
A Phase 2 Study of Vosoritide in Children With Idiopathic Short Stature
Leah Tyzinksi - Leah.Tyzinski@cchmc.org
ALL
3 years to 11 years old
PHASE2
NCT06382155
Key
• Height assessment corresponding to a height Z-score of ≤ -2.25 SDs in reference to the general population of the same age and sex, as calculated using the Centers for Disease Control and Prevention (CDC) growth charts
• If participant is ≥ 5 years at Screening,must be Tanner Stage I to be eligible for enrollment and randomization3. Historic stimulation test result with serum or plasma GH level greater than 10 μg/L or serum IGF-1 in the normal range for age (≥ -1.00 SDs and ≤+2.00 SDs). Key Exclusions:
• Known chromosomal imbalance or genetic variant causing short stature syndrome, including but not limited to Laron syndrome, Prader-Willi syndrome, Russell-Silver Syndrome, Turner syndrome, disproportionate skeletal dysplasias, abnormal SHOX gene analysis, or Rasopathy (including Noonan syndrome), ACAN deficiency.
• Previous treatment with a growth promoting agent
Inclusion Criteria:
• Height assessment corresponding to a height Z-score of ≤ -2.25 SDs in reference to the general population of the same age and sex, as calculated using the Centers for Disease Control and Prevention (CDC) growth charts
• If participant is ≥ 5 years at Screening,must be Tanner Stage I to be eligible for enrollment and randomization3. Historic stimulation test result with serum or plasma GH level greater than 10 μg/L or serum IGF-1 in the normal range for age (≥ -1.00 SDs and ≤+2.00 SDs). Key Exclusions:
• Known chromosomal imbalance or genetic variant causing short stature syndrome, including but not limited to Laron syndrome, Prader-Willi syndrome, Russell-Silver Syndrome, Turner syndrome, disproportionate skeletal dysplasias, abnormal SHOX gene analysis, or Rasopathy (including Noonan syndrome), ACAN deficiency.
• Previous treatment with a growth promoting agent
DRUG: Vosoritide Injection, DRUG: Human Growth Hormone, DRUG: Placebo
Idiopathic Short Stature
Evaluation of Analgesia for Cardiac Elective Surgery in Children (PRECISE)
Isabelle Allen - isabelle.allen@cchmc.org
ALL
3 years to 18 years old
PHASE3
NCT06626035
Inclusion Criteria:
* Children aged 3-years - \<18 years
* ASA physical status 1, 2, or 3
* Participant or legal guardian can speak and read English or Spanish
* Undergoing the following cardiac surgeries (Categories 1 \& 2) that are associated with significant acute surgical pain
STS Category 1:
* ASD, PFO closure
* VSD repairs,
* Aortic stenosis sub-valvular repair
* ASD and Partial anomalous venous return repair
* AV canal transitional
* Conduit replacement
* Valve replacement (AVR, PVR)
* TOF repair without ventriculostomy
STS Category 2:
* Glenn shunt (on Bypass only)
* Fontan surgery (on Bypass only)
* Pulmonary artery plasty (main)
* Left Atrium (LA) to Pulmonary Artery (PA) conduit replacement.
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 (have a sleep study with an AHI index score more than 10 or clinical signs of sleep disordered breathing - snoring, daytime drowsiness)
* 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
Pediatric Cardiac Surgery
A Phase 2 Study of TCP-25 Gel in Patients With Epidermolysis Bullosa, STEP-study (STEP)
- bret.augsburger@cchmc.org
ALL
4 years and over
PHASE2
NCT06594393
Inclusion Criteria:
* Male or female patients with documented diagnosis of DEB or JEB, confirmed by genetic testing and/or by a skin biopsy with immunofluorescence mapping.
* Patients ≥4 years old. Note: Initially, patients ≥12 years will be enrolled. Enrollment will be open to 4 to 11 year old pediatric patients (both inclusive), after a DMC reviews and provides a positive opinion regarding the safety and tolerability of the IMP in at least 3 patients 12 to 18 years old who have completed at least 4 weeks of IMP use.
Exclusion Criteria:
* The patient has any subtype of EB other than DEB or JEB.
* The patient is currently being treated or planned to be treated with systemic antibiotics.
Note: Use of preventive and/or anti-inflammatory antibiotic treatment, including doxycycline, on an established treatment regimen (stable dose for ≥6 weeks before the Baseline Visit) is permitted. Use of topical antibiotics on the index wounds within 7 days before the Baseline Visit is prohibited.
• Use of systemic corticosteroids \>0.2 mg/kg prednisone dose equivalent per day within 30 days or use of topical corticosteroids on index wounds within 7 days before the Screening Visit.
Note: Corticosteroids for inhalation, ophthalmic, or intranasal use are permitted.
• The patient has a history of or current malignancy over the index wound, eg, basal cell carcinoma or squamous cell carcinoma. DRUG: TCP-25 gel, DRUG: Vehicle (placebo)
Epidermolysis Bullosa (EB), Dystrophic Epidermolysis Bullosa, Junctional Epidermolysis Bullosa
epidermolysis bullosa, topical treatment
HeartGPS: A Study Exploring the Effects of a Psychological Intervention for Parents and Their Babies After Prenatal Cardiac Diagnosis (HeartGPS)
- heartgps@cchmc.org
ALL
18 years and over
NA
NCT06175104
Inclusion Criteria
• Pregnant person carrying a fetus diagnosed with single ventricle congenital heart disease (CHD).
• Single ventricle CHD diagnosis between 16 and 30 weeks gestation.
• Singleton pregnancy.
• Pregnant person is planning to continue with the pregnancy.
• Pregnant person is able to participate and complete study assessments in English. Exclusion Criteria
• Fetus with comorbid condition with a predictable adverse impact on neurodevelopment (e.g., DiGeorge Syndrome).
• Fetal or maternal medical condition determined by treating physician to be contraindicative to study participation.
• Parent with an untreated major psychiatric condition, substance use disorder, or other circumstances that would interfere with study engagement or safe participation in the trial.
• Parent with a moderate to severe intellectual disability.
• Parent age \<18 years.
• Surrogate for pregnancy. Prenatal administration of oral or intravenous corticosteroids for fetal lung maturation will be recorded but are not a reason for exclusion.
• Pregnant person carrying a fetus diagnosed with single ventricle congenital heart disease (CHD).
• Single ventricle CHD diagnosis between 16 and 30 weeks gestation.
• Singleton pregnancy.
• Pregnant person is planning to continue with the pregnancy.
• Pregnant person is able to participate and complete study assessments in English. Exclusion Criteria
• Fetus with comorbid condition with a predictable adverse impact on neurodevelopment (e.g., DiGeorge Syndrome).
• Fetal or maternal medical condition determined by treating physician to be contraindicative to study participation.
• Parent with an untreated major psychiatric condition, substance use disorder, or other circumstances that would interfere with study engagement or safe participation in the trial.
• Parent with a moderate to severe intellectual disability.
• Parent age \<18 years.
• Surrogate for pregnancy. Prenatal administration of oral or intravenous corticosteroids for fetal lung maturation will be recorded but are not a reason for exclusion.
BEHAVIORAL: HeartGPS
Heart Defects, Congenital, Anxiety in Pregnancy, Depression, Postpartum, Trauma, Psychological, Neurodevelopmental Disorders
Congenital Heart Disease, Prenatal, Mental Health, Neurodevelopment, Neurobehavior, Fetal Cardiology, Psychological Intervention, Mother-Infant Attachment, Mother-Infant Bonding, Medical Traumatic Stress, Neuroimaging, Brain Development, Fetal Neuroimaging, Perinatal Mental Health, Medical Psychology
Heart Institute Biobank & Registry for Adult Congenital Heart Disease and Related Disorders (HIBR-ACHD)
Olivia Croweak - 0livia.croweak@cchmc.org
ALL
16 years and over
NCT07477197
Inclusion Criteria:
• Any person ≥ 16 years-old suspected of having or diagnosed with congenital heart disease (CHD), other cardiovascular disease (CVD), pulmonary hypertension, connective tissue disease, or genetic syndrome/diagnosis.
• Additionally, a cohort (Control group A) of control subjects will be enrolled, again ≥16 years-old, self-reported non-smokers without a known history of diabetes mellitus, myocardial infarction, stroke, heart failure, or chronic kidney disease. These controls will be either:
• A family member or other person accompanying a patient to a clinical encounter; or,
• A volunteer recruited via an advertisement; or,
• Another person who volunteers to enroll in HIBR-ACHD.
• A cohort (Control group B) of comparison subjects who do not have CHD, but have a diagnosis of heart failure or pulmonary hypertension.
Exclusion Criteria:
* Unable to provide informed consent/assent personally or via a legal guardian.
* Considered unsafe to collect the biospecimen determined by either a clinical provider or an HIBR-ACHD investigator.
* Overnight hospitalization for non-obstetric reason with discharge in the prior 30 days. Adult Congenital Heart Disease, Pulmonary Hypertension, Connective Tissue Disease, Other Cardiovascular Conditions
ACHD, Adult Congenital Heart Disease
Heart Institute BioRepository (HIBR) for Pediatric Heart Disease (HIBR)
Olivia Croweak - olivia.croweak@cchmc.org
ALL
NCT07478354
Inclusion Criteria
* Any fetus, child or adult at risk of or diagnosed with Pediatric Heart Disease (PHD) or Cardiovascular Disease (CVD)
* Any HI patient, including the following types of encounters: Surgery or Cardiac Catheterization or Advanced Imaging encounters, Inpatient, including Cardiology service, consultation patients and Fetal Delivery, and Outpatient, including all HI-associated clinics and consultation services
* Any female carrying a fetus with a suspected cardiac diagnosis
Exclusion Criteria
* Legal guardian unauthorized to consent
* Families who choose Palliative care during pregnancy
Cardiovascular Diseases (CVD)
cardiovascular disease, Pediatric Heart disease
A Study to Find the Highest Dose of Cedazuridine and Decitabine Combination With Filgrastim as a Treatment Option After Hematopoietic Stem Cell Transplant in Children With High-Risk Acute Myeloid Leukemia
- cancer@cchmc.org
ALL
Up to 21 years old
PHASE1
NCT07012044
Inclusion Criteria:
* STEP 0: Patient must be ≤ 21 years of age
* PLEASE NOTE: Eligibility criteria to enroll onto Step 1 for the treatment trial is ≤ 21 years of age at the time of Step 1 enrollment. Please plan accordingly to ensure that patients who are screened with Step 0 will be at an eligible age at the time of enrollment onto Step 1. Patients who are 21 at the time of screening who turn 22 at the time of enrollment onto Step 1 will not be eligible to enroll onto the study
* STEP 0: Patients with newly diagnosed high risk\* de novo AML, newly diagnosed therapy-related AML, relapsed, or refractory AML. in complete remission at the time of transplant. Patients with a history of isolated or combined central nervous system (CNS) or extramedullary disease are eligible if they have no evidence of active CNS or extramedullary disease at the time of trial enrollment (Step 0) and treatment enrollment (Step 1). Eligible patients with histories of isolated or combined CNS or extramedullary disease at time of relapse are required to be in complete remission at time of transplant to be eligible for this study
* Based on risk criteria adopted by the AAML1831 study
* STEP 0: Patient must plan to have bone marrow sample submitted to Hematologics within 14 days prior to the start of conditioning regimen for HCT.
* Note: In order to be eligible to enroll onto Step 1 to receive treatment on this study, pre-HCT disease status must be assessed prior to receiving HCT. AML must be in complete remission (Children's Oncology Group \[COG\]-complete remission \[CR\], COG-complete remission with partial recovery of platelelt count \[CRp\], COG-complete remission with incomplete blood count recovery \[Cri\], with or without detectable minimal residual disease \[MRD\]); bone marrow CR must be assessed by central flow cytometry performed at Hematologics prior to the start of the conditioning regimen
* STEP 0: Human immunodeficiency virus (HIV)-infected patients are eligible for this trial if the following criteria are met:
* No history of HIV complications with the exception of CD4 count \< 200cells/mm\^3
* No antiretroviral therapy with overlapping toxicity such as myelosuppression
* CD4 count \> 500 cells/mm\^3 prior to the diagnosis of newly diagnosed, relapsed, refractory AML.
* HIV viral loads below the limit of detection within 6 months, as long as the patient is NOT receiving anti-retroviral agents that may interact with ASTX727.
* No history of highly active antiretroviral therapy (HAART)-resistant HIV
* STEP 0: Patients must be receiving an allogeneic (related, unrelated, and mismatched related, including haploidentical) marrow, peripheral blood, or cord blood transplant for the first time
* STEP 0: HCT conditioning regimen must be planned to begin within 14 days after bone marrow assessment to determine disease status
* STEP 0: Conditioning regimen must be myeloablative and include high dose busulfan, or treosulfan, or total body irradiation
* STEP 0: Patients must not have received prior exposure to ASTX727. Note that patients may have had prior exposure to decitabine
* STEP 1: Patient must be ≤ 21 years of age at the time of study enrollment to step 0 and step 1
* STEP 1: Patients must have a body surface area ≥ 1m\^2 at enrollment to step 1
* STEP 1 (PRE-HCT): AML must be in complete remission (COG-CR, COG-CRp, COG-Cri), with or without detectable MRD; bone marrow CR must be assessed by central flow cytometry performed at Hematologics. Disease assessment must be performed within 14 days prior to the start of HCT conditioning regimen
* Patients with CNS or extramedullary disease within 14 days prior to the start of the HCT condition regimen are not eligible
* STEP 1 (POST-HCT): AML must be in complete remission (COG-CR, COG-CRp, COG-CRi). Bone marrow evaluation must show CR with no detectable minimal residual disease (MRD negative by central flow cytometry at Hematologics)
* Note: Disease assessment is required to be performed within 14 days prior to enrollment onto Step 1
* Patients with CNS or extramedullary disease post-HCT are not eligible
* STEP 1: 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 Karnofsky performance score ≥ 50 or Lansky play-performance scale score ≥ 50
* STEP 1: Patients must have fully recovered from the acute toxicities related to the conditioning regimen and the transplant. If, after 42-100 days post-transplant, the eligibility criteria are met, the patient is considered to have recovered adequately
* STEP 1: Platelet count ≥ 50,000 µL (without requirement for platelet transfusion within the last 7 days)
* STEP 1: Hemoglobin ≥ 8.0 g/dL at baseline (may receive red blood cell \[RBC\] transfusions)
* STEP 1: Absolute neutrophil count ≥ 1,000 µL with no myeloid growth factor support within the last 3 days
* Estimated glomerular filtration rate (GFR) (eGFR) ≥ 60 mL/min/1.73 m\^2 "Bedside" Schwartz formula (2009) OR
* OR- A 24 hour urine creatinine clearance ≥ 60 mL/min/1.73 m\^2
* A GFR ≥ 60 mL/min/1.73 m\^2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard)
* Note: Estimated GFR (eGFR) from cystatin C or other estimates not listed above are not acceptable for determining eligibility
* STEP 1: Bilirubin (total or sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) for age
* STEP 1: Alanine aminotransferase (ALT) ≤ 3 x ULN
* STEP 1: Aspartate aminotransferase (AST) ≤ 3 x ULN
* STEP 1: Albumin ≥ 2 g/dL
Exclusion Criteria:
* STEP 0: Patients with known inherited marrow failure syndromes, including, but not limited to Fanconi Anemia, Dyskeratosis congenita, and Shwachman-Diamond syndrome
* STEP 0: Known or suspected hypersensitivity to filgrastim, decitabine or cedazuridine (ASTX727)
* STEP 0: Patients who have received a prior solid organ transplantation are not eligible
* STEP 1: ASTX727 can cause fetal harm when administered to pregnant women. 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 (eg, male or female condom) for the duration of the study. Abstinence is an acceptable method of birth control. Women of childbearing potential must use highly effective contraception during treatment with ASTX727 and for at least 6 months after the last dose. Men with female partners of childbearing potential should be advised to practice highly effective contraceptive measures of birth control and not to father a child while receiving treatment with decitabine and for 3 months after the last dose. Breastfeeding is not allowed during the study and for at least 2 weeks after the last dose of study drug
* STEP 1: Patients who are currently receiving another investigational drug are not eligible
* STEP 1: Patients who are currently receiving other anti-cancer agents are not eligible. Patients receiving intrathecal chemotherapy in the prior 14 days are eligible
* STEP 1: Patients receiving or for whom there is a plan to administer anticancer non-protocol therapy, radiation therapy or immunotherapy during the study period are not eligible (note that prophylactic use of chemotherapeutic agents for graft versus host disease \[GVHD\] is allowed, e.g. methotrexate for GVHD prophylaxis). Intrathecal cytarabine administered at the discretion of the treating physician throughout maintenance therapy is allowed
* STEP 1: Drugs known to be metabolized by cytidine deaminase (CDA) should not be given (such drugs include cytarabine, gemcitabine, azacitidine, vidarabine, zalcitabine, zidovudine, telbivudine, didanosine, stavudine, lamivudine, abacavir, emtricitabine, entecavir, trifluridine, tenofovir and adefovir) on days when ASTX727 is administered and for 24 hours thereafter
* STEP 1: Patients is not able to swallow intact tablets. Nasogastric or G tube administration is not allowed
* STEP 1: Patient is not able to start ASTX727 and filgrastim (rh-GCSF) between day 42 and day 100 following completion of allo-HCT. If, after enrollment, protocol therapy is started more than 100 days following allo-HCT, the patient will be removed from protocol therapy
* STEP 1: Patients with graft loss are not eligible
* STEP 1: Patients with steroid refractory or dependent acute GVHD are not eligible. Patients must be on \< 1 mg/kg/day of methylprednisolone (or equivalent prednisone/prednisolone dose) that is being tapered. Patients must not be on any second line systemic therapies. Continued GVHD prophylaxis with calcineurin inhibitors, sirolimus, abatacept or mycophenolate mofetil is acceptable
* STEP 1: Patients who have an uncontrolled viral, bacterial, fungal, or protozoal infection are not eligible
* STEP 1: Patients with active transplant associated thrombotic microangiopathy with ongoing hemolysis and need treatment (e.g. eculizumab) are not eligible
* STEP 1: Patients with sinusoidal obstruction syndrome with ongoing need for treatment (e.g. defibrotide, diuresis, supplemental oxygen) are not eligible
* STEP 1: Idiopathic pneumonitis syndrome or other non-infectious lung injury requiring ongoing treatment (corticosteroids, tumor necrosis factor \[TNF\] inhibitors, or other biologics) or supplemental oxygen are not eligible
* STEP 1: 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: Bone Marrow Aspiration, PROCEDURE: Bone Marrow Biopsy, DRUG: Decitabine, DRUG: Decitabine and Cedazuridine, BIOLOGICAL: Filgrastim, PROCEDURE: Imaging Procedure, PROCEDURE: Lumbar Puncture
Acute Myeloid Leukemia Post Cytotoxic Therapy, Recurrent Acute Myeloid Leukemia, Refractory Acute Myeloid Leukemia
The Baby Duchenne Study: Characterizing Developmental and Clinical Outcomes in the First Three Years in Children With Duchenne Muscular Dystrophy (BABY DUCHENNE)
Angela Edmondson - angela.edmondson@cchmc.org
MALE
0 days to 3 years old
NCT07092540
Inclusion Criteria:
* Male child between birth and 3.0 years of age at time of enrollment.
* A confirmed and documented pathogenic or likely pathogenic variant in the DMD gene.
* Ability of parent/guardian to understand and provide written informed consent (signing Parental Permission and Consent Form).
* Willingness of parent/guardian to comply with the protocol Schedule of Activities, including all study site visits.
Exclusion Criteria:
* Female
* Presence of any confirmed genetic disease, other than DMD, that could impact early development, which, in the opinion of the PI, may confound interpretation of developmental progress.
* Presence of any significant medical condition (i.e., extreme prematurity, hypoxic ischemic encephalopathy) which, in the opinion of the PI, may confound interpretation of the clinical course of DMD.
* Inability/unwillingness of parent/guardian to provide written permission (sign PPF) or to comply with the protocol Schedule of Activities. Duchenne Muscular Dystrophy (DMD)
New born screening
Study of Cabozantinib With Selumetinib for Plexiform Neurofibromas (NF113)
Lori Backus - lori.backus@cchmc.org
ALL
16 years and over
PHASE1
NCT06502171
• 0 INCLUSION CRITERIA
• 1. All participants must have a diagnosis of NF1 based on the 2021 revised consensus criteria.
• 2. 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.
• 2.1. For participants enrolled for tumor progression, progression is defined as: Presence of new PN on MRI or CT (documented by comparison with prior MRI or CT), OR A measurable increase in PN size (≥ 20% increase in the volume, or a ≥ 13% increase in the product of the two longest perpendicular diameters, or a ≥ 6% increase in the longest diameter) documented by comparison of two scans (MRI or CT) in the time period of 18 months or less prior to evaluation for this study.
• 2.2. For participants enrolled for tumors causing "significant disfigurement" without meeting another criterion (i.e., not progressive or causing other significant morbidity), eligible tumors will be limited to tumors of the head \& neck or those on other areas of the body that are unable to be concealed by standard garments. In order to enroll a participant with PN for these indications, photographs must be reviewed by a Study Chair and/or Co-Chair for decision regarding participant eligibility prior to enrollment.
• 3. Disease status: 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.
• 4. Age: Participants must be ≥16 years of age at the time of study entry.
• 5. Performance Level: Participants must have Karnofsky ³ 50%. Note: Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for assessing the performance score.
• 6. Body Surface Area (BSA): Participants must have a BSA of 1.0 m2 or greater.
• 7. Organ Function Requirements:
• 7.1. Adequate Bone Marrow Function Defined as: Absolute neutrophil count (ANC) ≥ 1500/µL without granulocyte colony-stimulating factor support. White blood cell count ≥ 2500/µL Platelet count ³ 100,000/mL without transfusion Hemoglobin ³10.0 gm/dL (\>5 days between enrollment and last RBC transfusion)
• 7.2. Adequate Renal Function Defined as: Maximum serum creatinine based on age/gender as per institutional standards OR a creatinine clearance, radioisotope GFR, or calculated creatinine clearance using the Cockcroft-Gault equation ³70ml/min/1.73 m2. Cockcroft-Gault equation: * Males: (140 - age) x weight (kg)/(serum creatinine \[mg/dL\] × 72) * Females: \[(140 - age) x weight (kg)/(serum creatinine \[mg/dL\] × 72)\] × 0.85 Urine protein/creatinine ratio (UPCR) ≤ 1 mg/mg (≤ 113.2 mg/mmol), or 24-h urine protein ≤ 1 g.
• 7.3. Adequate Liver Function Defined as: Total bilirubin (sum of conjugated + unconjugated) £ 1.5x upper limit of normal (ULN) for age (for participants with Gilbert's disease ≤3x ULN), and Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) \< 2.5x the upper limit of normal (ULN). Serum albumin ³ 2.8 g/dL. PT/INR and partial thromboplastin time (PTT) test \< 1.3x the laboratory ULN
• 7.4. Adequate Thyroid Function Defined as: ≤ Grade 1 or adequately managed asymptomatic Grade 2 hypothyroidism.
• 7.5. CPK level within normal limits within 14 days from the start of treatment.
• 7.6. Normal pancreatic function: amylase and lipase levels ≤ 1.5 x ULN
• 7.7. Blood pressure within upper limit of normal as defined below. Antihypertensives are permissible to achieve blood pressure within ULN, however must be on stable antihypertensive regimen with no adjustments within 30 days of enrollment. In adolescents, a blood pressure (BP) ≤ 90th percentile for age, height, and sex. In adults (³18 years of age), a systolic blood pressure ≤130 mmHg and a diastolic pressure of ≤80 mmHg.
• 8. Major surgery: Only participants who are not anticipated to need major surgery within 3 months after enrollment are eligible.
• 9. Sexually active fertile 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 is an acceptable method of birth control for both men and women. Persons of childbearing potential will be given a pregnancy test within 7 days prior to first dose of study treatment and must have a negative urine or serum pregnancy test.
• 10. Written informed consent must be obtained from all participants (\>18 years of age) or their legal guardians (if the participant is \<18 years of age). Participants or legal guardians must be capable of understanding and complying with the protocol requirements and must have signed the informed consent document. Participants unable to provide informed consent/assent will NOT be enrolled on this study.
• 11. Willingness to avoid excessive sun exposure and use adequate sunscreen protection if sun exposure is anticipated.
• 12. Willingness to avoid the ingestion of grapefruit and Seville oranges (as well as other products containing these fruits, e.g., grapefruit juice or marmalade) during the study, as these may affect selumetinib metabolism.
• 0 EXCLUSION CRITERIA
• 1. Evidence of an 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 or radiation therapy.
• 2. Patients with high-grade glioma, atypical or 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.
• 3. Dental braces or prosthesis that interfere with volumetric analysis of the neurofibroma(s).
• 4. Prior Therapy: 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: Must not have received within 28 days of entry onto this study.
• 5. Hematopoietic growth factors: Must not have received a growth factor that supports platelet, red or white cell number or function within 14 days of initiation of therapy.
• 6. Biologic (anti-neoplastic agent): At least 28 days (or 5 half-lives whichever is longer) since the completion of therapy with a biologic agent. For agents that have known adverse events occurring beyond 28 days after administration (or 5 half-lives whichever is longer), this period must be extended beyond the time during which adverse events are known to occur. These participants must be discussed with the Study Chair on a case-by-case basis.
• 7. Investigational Drugs: At least 28 days (or 5 half-lives whichever is longer) since the completion of therapy with an investigational drug or systemic anticancer treatment. For agents that have known adverse events occurring beyond 28 days after administration (or 5 half-lives whichever is longer), this period must be extended beyond the time during which adverse events are known to occur. These participants must be discussed with the Study Chair on a case-by-case basis. \- Prior treatment with cabozantinib or selumetinib is permitted for participants on Phase 1 of this study only (not Phase 1b/2). Participants may have previously received cabozantinib and/or a MEK inhibitor but not simultaneously. If participants have received either cabozantinib or selumetinib previously, they must have tolerated either medication at the recommended entry doses for this study or greater and must not have discontinued therapy due to toxicity. Participants who have received the combination of cabozantinib with any MEK inhibitor previously will not be eligible. Prior treatment with cabozantinib and/or selumetinib will not be permitted for participants on Phase 1b or Phase 2.
• 8. Radiation therapy: 6 months from involved field radiation to index PN(s) must have elapsed prior to study entry; ³ 6 weeks must have elapsed if participant has received radiation to areas outside index PN(s) Participants who received radiation to the orbit at any time previously are not eligible. \>12 weeks must have elapsed between systemic treatment with radionuclides and first dose of study treatment. Participants with clinically relevant ongoing complications from prior radiation therapy are not eligible.
• 9. Surgery:
• 9.1. Participants are not eligible if complete resection of a PN with acceptable morbidity is feasible, or if a participant with a feasible surgical option with minimal risk for surgical morbidity refuses surgery. Participants who underwent surgery for a progressive PN will be eligible to enter the study after the surgery, provided the PN was incompletely resected and is measurable.
• 9.2. Any major surgery within 3 months before first dose of study treatment.
• 9.3. Any minor surgeries (e.g., the placement of an implanted vascular device, tooth extractions, biopsy, or an invasive operative procedure for procurement of tissue samples or body fluids using a needle or trocar, other than routine peripheral venous access) within 1 month before first dose of study treatment.
• 9.4. Participants must have complete wound healing from major surgery or minor surgery before first dose of study treatment. Participants with clinically relevant ongoing complications from prior surgery are not eligible.
• 10. Concomitant anticoagulation with coumarin agents (e.g., warfarin), low molecular weight heparins, direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g., clopidogrel). Allowed anticoagulants are the following: Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines)
• 11. Clinically significant hematuria, hematemesis, or hemoptysis of \>0.5 teaspoon (2.5ml) of red blood, or other history of significant bleeding (e.g., pulmonary hemorrhage) within 12 weeks before first dose of study treatment.
• 12. Known cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease manifestation.
• 13. Cardiovascular disorders: 2.13.1. Congestive heart failure New York Heart Association Class 2-4, unstable angina pectoris (Canadian Cardiovascular Society grade II-IV despite medical therapy), prior or current cardiomyopathy, or severe valvular heart disease, baseline left ventricular ejection fraction (LVEF) below the LLN or \<55% measured by echocardiography or institution's LLN for MUGA, serious cardiac arrhythmias including atrial fibrillation.
• 13.2. Stroke (including transient ischemic attack \[TIA\]), acute coronary syndrome or myocardial infarction (MI), or other ischemic event, or thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 6 months before first dose of study treatment.
• 13.3. Participants with a diagnosis of incidental, subsegmental PE or DVT within 6 months are allowed if stable, asymptomatic, and treated with a stable dose of permitted anticoagulation (aspirin) for at least 1 week before first dose of study treatment.
• 13.4. Baseline QTc interval \>450 msec
• 14. Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation:
• 14.1. The participant has evidence of tumor invading the GI tract, active peptic ulcer disease, inflammatory bowel disease (e.g., Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis, acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction.
• 14.2. Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose of study treatment. Note: Complete healing of an intra-abdominal abscess must be confirmed before first dose of study treatment.
• 15. Ophthalmologic conditions:
• 15.1. Current or history of central serous retinopathy
• 15.2. Current or history of retinal vein occlusion
• 15.3. Known intraocular pressure (IOP) \>21 mmHg (or ULN adjusted by age) or uncontrolled glaucoma (irrespective of IOP). Participants with known glaucoma and increased IOP who do not have meaningful vision (light perception only or no light perception) and are not experiencing pain related to the glaucoma, may be eligible after discussion with the study chair. Participants with orbital plexiform neurofibromas should have IOP measured prior to enrollment.
• 15.4. Participants with any other significant abnormality on ophthalmic examination should be discussed with the Study Chair for potential eligibility.
• 15.5. Ophthalmological findings secondary to long-standing optic pathway glioma (such as visual loss, optic nerve pallor or strabismus) or long-standing orbito-temporal PN (such as visual loss, strabismus) will NOT be considered a significant abnormality for the purposes of the study.
• 16. Other clinically significant disorders that would preclude safe study participation, including:
• 16.1. Serious non-healing wound, ulcer, or bone fracture.
• 16.2. Uncompensated/symptomatic hypothyroidism.
• 16.3. Moderate to severe hepatic impairment (Child-Pugh B or C).
• 16.4. Active infection
• 16.5. A known history of HIV seropositivity or known immunodeficiency. HIV testing will not be required as part of this trial, unless HIV is clinically suspected.
• 16.6. Uncontrolled diabetes, severe malnutrition, chronic liver or renal disease
• 16.7. History of organ transplant
• 17. Pregnant or lactating women.
• 18. Inability to swallow tablets.
• 19. Previously identified allergy or hypersensitivity to components of the study treatment formulations.
• 20. Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of cabozantinib or selumetinib (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection).
• 21. Participants who require chronic concomitant treatment of moderate/strong CYP3A4 inducers or inhibitors (Appendix XIII). While not an exclusion criterion, unless clinically indicated, participants should avoid taking other additional non-study medications that may interfere with the study medications. Participants should avoid medications that are known to either induce or inhibit the activity of hepatic microsomal isoenzymes CYP1A2, and CYP2C19, as this may interfere with the metabolism of selumetinib (Appendix XIII).
• 22. Participants with a history of significant noncompliance to medical regimens, are unwilling to or unable to comply with the protocol, or who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study.
DRUG: Cabozantinib Oral Tablet, DRUG: Selumetinib Oral Capsule
Neurofibromatosis 1, Plexiform Neurofibroma
adolescents, adults
Study to Learn About Safety, Tolerability, and Immune Response of a Catch-up Pneumococcal Vaccine in Children and Adolescents
- VaccineResearch@cchmc.org
ALL
15 months to 17 years old
PHASE3
NCT07660198
Inclusion Criteria:
Cohort 1 (Participants ≥15 Months to \<2 Years of Age) Healthy toddlers and children ≥15 months to \<2 years of age with documentation of prior receipt of PCV.
Cohort 2 (Participants ≥2 Years to \<5 Years of Age) Healthy toddlers and children ≥2 years to \<5 years of age with documentation of prior receipt of PCV if applicable.
Cohort 3 (Participants ≥5 Years to \<18 Years of Age) Healthy children ≥5 years to \<18 years of age with documentation of prior receipt of PCV (if applicable). A negative urine pregnancy test is required for individuals of childbearing potential (IOCBP). IOCBP or participants able to father must also agree to use a highly effective method of birth control.
Exclusion Criteria:
All Cohorts (Participants ≥15 Months to \<18 Years of Age)
Children with significant medical, psychiatric, or neurological conditions (eg, immunodeficiency or history of seizure); or a history of confirmed invasive pneumococcal infection in the past will be excluded from enrolment in the trial BIOLOGICAL: PG4, BIOLOGICAL: 20-valent pneumococcal conjugate vaccine (20vPnC)
Pneumococcal Disease
First-in-human Study of a New Treatment (4A10) for Patients With Relapsed or Hard-to-treat Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma, Focused on Safety and How the Drug Behaves in the Body and Early Signs of Effect. (ALT-101)
- cancer@cchmc.org
ALL
18 years and over
PHASE1
NCT07586618
Key
• Confirmed diagnosis of T/B-ALL or T/B-LL
• Relapsed or refractory disease without curative options
• Adequate organ function and performance status Key
• Patients with CNS3 disease
• Patients with DNA fragility syndromes (e.g., Fanconi, Bloom), trisomy 21 (Down Syndrome)
• Prior exposure to anti-CD127 therapies
• Uncontrolled infections
Inclusion Criteria:
• Confirmed diagnosis of T/B-ALL or T/B-LL
• Relapsed or refractory disease without curative options
• Adequate organ function and performance status Key
Exclusion Criteria:
• Patients with CNS3 disease
• Patients with DNA fragility syndromes (e.g., Fanconi, Bloom), trisomy 21 (Down Syndrome)
• Prior exposure to anti-CD127 therapies
• Uncontrolled infections
DRUG: 4A10
Lymphoblastic Lymphoma, Acute Lymphoblastic Leukemia ALL
Leukemia, Refractory, Relapsed
BOND: Direct Breastfeeding to Enhance Maternal and Infant Health in Congenital Heart Disease
- olivia.cleary@cchmc.org
ALL
18 years and over
NA
NCT07582848
Both mothers and infants are study participants.
Inclusion criteria:
• Pregnant individual carrying a fetus diagnosed with CHD or biological mother of an infant diagnosed with CHD in the neonatal period.
• Fetus or newborn with CHD anticipated to require cardiac surgery or transcatheter intervention in the first 30 days of life.
• Admission to the ICU (either CICU or NICU) at participating center in 1st week of life and for whom cardiac surgical or transcatheter intervention is anticipated in the first 30 days of life.
• Willing to comply with protocol and provide written informed consent
• Mother, fetal, or infant medical condition determined by a treating clinician to be contraindicative to study participation.
• Mother with a severe, untreated psychiatric condition, substance use disorder, or other circumstances that, in the opinion of the investigator, would interfere with engagement with study tasks or safe participation in the trial.
• Mother with a moderate to severe intellectual disability or is otherwise unable to provide informed consent.
• Infant birthweight \<3rd percentile for gestational age
• Infant gestational age \< 36 weeks
• Infant with known genetic disorder likely to impact breastfeeding, such as trisomy 21 or cleft palate
• Medical condition or congenital anomaly that precludes safe direct breastfeeding for the infant as determined by investigator
• Pregnant individual carrying a fetus diagnosed with CHD or biological mother of an infant diagnosed with CHD in the neonatal period.
• Fetus or newborn with CHD anticipated to require cardiac surgery or transcatheter intervention in the first 30 days of life.
• Admission to the ICU (either CICU or NICU) at participating center in 1st week of life and for whom cardiac surgical or transcatheter intervention is anticipated in the first 30 days of life.
• Willing to comply with protocol and provide written informed consent
Exclusion Criteria:
• Mother, fetal, or infant medical condition determined by a treating clinician to be contraindicative to study participation.
• Mother with a severe, untreated psychiatric condition, substance use disorder, or other circumstances that, in the opinion of the investigator, would interfere with engagement with study tasks or safe participation in the trial.
• Mother with a moderate to severe intellectual disability or is otherwise unable to provide informed consent.
• Infant birthweight \<3rd percentile for gestational age
• Infant gestational age \< 36 weeks
• Infant with known genetic disorder likely to impact breastfeeding, such as trisomy 21 or cleft palate
• Medical condition or congenital anomaly that precludes safe direct breastfeeding for the infant as determined by investigator
OTHER: Breastfeeding clinical practice guideline (CPG) for congenital heart disease (CHD)
Congenital Heart Disease (CHD)
Direct breastfeeding, CHD, Infant neurodevelopment, Maternal Mental Health
Assessing Pulmonary Changes in HSCT
Ashley Borden, MPH - ashley.borden@cchmc.org
ALL
3 years and over
PHASE1
NCT07823036
Inclusion Criteria:
* Ages 3 years and older
Exclusion Criteria:
* Pregnancy or positive pregnancy test
* Baseline oximetry at MRI visit of less than 90% on room air or less than 90% on a previously prescribed dosage of oxygen delivered by nasal cannula. In some cases of cardiorespiratory disease, if the participant is referred to this research study by their treating physician and considered stable for imaging, the cardiorespiratory criteria will be 5% of their clinical baseline. This should be documented in the research record upon referral of a participant that meets this scenario.
* Any condition in the opinion of the investigator that would make the participant unable to tolerate the MRI procedure (e.g., neurocognitive delay, behavioral issues).
* Standard MRI exclusions (e.g., metal, incompatible implants). DRUG: Hyperpolarized 129 Xenon
HSCT, Respiratory, Gas Exchange Impairment
A Pragmatic Clinical Trial of the WE BEAT Well-Being Education Program in Adolescent Congenital Heart Disease: WE BEAT CHD Study (PHN WBC)
Elise Pickering - Elise.Pickering@cchmc.org
ALL
12 years to 17 years old
NA
NCT07525843
Inclusion Criteria:
* Age 12-17 years old
* CHD of moderate or severe complexity (Class II/III, 2018 AHA/ACC ACHD, Table 4)
* English or Spanish language proficiency
* Receives cardiology care at a PHN or PHN auxiliary site
* Parent or guardian and participant willing to comply with protocol and provide written/electronic informed consent and assent
Exclusion Criteria:
* CHD of mild or simple complexity (Class I, 2018 AHA/ACC ACHD, Table 4)
* Prior heart transplant to treat CHD
* Heart disease that is not classified as structural CHD (e.g., connective tissue disease, genetic cardiomyopathy, or acquired heart disease)
* Cognitive or developmental conditions that limit program participation and/or ability to complete self-reported measures as determined by a primary cardiology clinician
* Suicidality, homicidality, or psychosis in the past 12 months as per medical chart review, clinician report, or eligibility screening
* Medically unable to participate (e.g., intubated, unable to respond verbally, active delirium) BEHAVIORAL: Telemedicine-based resiliency-building intervention
Patient-Reported Outcome Measures (PROMs), Pragmatic Trial, Adolescent Congenital Heart Disease, Resiliency-building Intervention, Resilience, Psychological, Telemedicine-Based Education
WE BEAT, Well-Being Education Program, Adolescent CHD, Pragmatic Clinical Trial, Telemedicine
Inspiring New Science In Guiding Healthcare in Turner Syndrome Registry (INSIGHTS)
Leah Tyzinksi - leah.tyzinski@cchmc.org
FEMALE
NCT05052606
Inclusion Criteria:
• Individuals with TS and TS variants as defined by the TS Clinical Practice Guideline definition (karyotype consistent with TS, phenotypic female, clinical feature(s) of TS)
• Informed consent/assent as appropriate
Exclusion Criteria:
a. Lack of a TS diagnosis on file OTHER: No intervention
Turner Syndrome
Standardizing Treatments for Pulmonary Exacerbations - Aminoglycoside Study (STOP360AG)
Kelly Thornton - Kelly.Thornton@cchmc.org
ALL
6 years and over
PHASE4
NCT05548283
Inclusion Criteria:
* All genders ≥ 6 years of age at Visit 1
* Documentation of a CF diagnosis
* Clinician intent to treat index CF PEx with a planned 14-day course of IV antimicrobials
* At least one documented Pa positive culture within two years prior to Visit 1
Exclusion Criteria:
* Participant is not pregnant
* No known renal impairment or history of solid organ transplantation
* No IV antimicrobial treatment, ICU admission, pneumothorax, or hemoptysis within 6 weeks prior to Visit 1
* No use of investigational therapies, new CF transmembrane conductance regulator (CFTR) modulators, or treatment for Nontuberculous mycobacteria (NTM) within 4 weeks prior to Visit 1
* No history of hypersensitivity, vestibular, or auditory toxicity with aminoglycosides
* No more than one day of IV aminoglycosides administered for the current PEx treatment prior to Visit 1 DRUG: Beta-lactam antibiotic, DRUG: Aminoglycoside
Cystic Fibrosis, Cystic Fibrosis Pulmonary Exacerbation
Cystic Fibrosis, CF, Cystic Fibrosis Pulmonary Exacerbation, aminoglycoside, beta-lactam, β-lactam, STOP, STOP360
Thoracotomy Versus Thoracoscopic Management of Pulmonary Metastases in Patients With Osteosarcoma
- cancer@cchmc.org
ALL
Up to 50 years old
PHASE3
NCT05235165
Inclusion Criteria:
* Patients must be \< 50 years at the time of enrollment.
* Patients must have =\< 4 nodules per lung consistent with or suspicious for metastases, with at least one of which being \>= 3 mm and all of which must be =\< 3 cm size.
* Note: Patient must have eligibility confirmed by rapid central imaging review.
* Lung nodules must be considered resectable by either open thoracotomy or thoracoscopic surgery. Determination of resectability is made by the institutional surgeon.
* Patients must have a histological diagnosis of osteosarcoma.
* Patients must have evidence of metastatic lung disease at the time of initial diagnosis, or at time of 1st recurrence following completion of therapy for initially localized disease.
* Patients with newly diagnosed disease must have completed successful gross tumor resection for their primary tumor or surgical local control of primary tumor must be planned to be performed simultaneously with thoracic surgery.
* Newly diagnosed patients must be receiving or recently completed (within 60 days) systemic therapy considered by the treating physician to be standard treatment for newly diagnosed osteosarcoma (eg, cisplatin-doxorubicin or ifosfamide-based drug regimens) at the time of enrollment on this study. Dose and drug modifications for toxicity do not exclude patients from participation.
* Patients at time of 1st recurrence must have completed systemic therapy for their initial primary tumor, considered by the treating physician to be standard treatment for newly diagnosed osteosarcoma (eg, cisplatin-doxorubicin or ifosfamide-based drug regimens) at the time of enrollment on this study. Dose and drug modifications for toxicity do not exclude patients from participation.
Exclusion Criteria:
* Patients with unresectable primary tumor.
* Patients with pulmonary metastatic lesions that would require anatomic resection (lobectomy or pneumonectomy) or lesions that are defined as "central" (i.e., central lesion involves or is proximal to segmental bronchi and peripheral is lesion distal to segmental bronchi).
* Patients with chest wall or mediastinal based metastatic lesions, or with significant pleural effusion.
* Patients with disease progression at either the primary or pulmonary metastatic site while on initial therapy. Note: Once the patient has been enrolled on the study, additional computed tomography (CT) scans are not anticipated prior to thoracic surgery. Note: Some variation in nodule size measurements over the course of pre-operative therapy is anticipated and does not qualify for exclusion unless deemed true disease progression by the primary treatment team.
* Patients with evidence of extrapulmonary metastatic disease.
* Patients who received therapeutic pulmonary surgery for lung metastasis prior to enrollment.
* 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. PROCEDURE: Biospecimen Collection, PROCEDURE: Computed Tomography, OTHER: Questionnaire Administration, PROCEDURE: Thoracoscopy, PROCEDURE: Thoracotomy
Metastatic Malignant Neoplasm in the Lung, Metastatic Osteosarcoma, Osteosarcoma
I-DECIDE After Bronchiolitis Hospitalization (I-DECIDE)
Ramya Ramya Adapa - RamyaSriLakshmi.Adapa@cchmc.org
ALL
0 months to 24 months old
NA
NCT07243652
Inclusion Criteria:
* Primary diagnosis of bronchiolitis, discharged by a generalist inpatient service from a non-ICU, non-emergency department, non-step down unit
Exclusion Criteria:
* Children with a history of gestational age \<28 weeks, chronic lung disease, complex or hemodynamically significant heart disease, immunodeficiency, or neuromuscular disease
* Children being discharged with home oxygen therapy OTHER: Moderate-Resource Implementation Strategy, OTHER: High-Resource Implementation Strategy
Bronchiolitis Acute
Mind Body Balance for Pediatric Migraine
Leigh Ann Chamberlin - LeighAnn.Chamberlin@cchmc.org
ALL
10 years to 17 years old
NA
NCT04715685
Inclusion Criteria:
* Diagnosis: Migraine with or without aura or chronic migraine that meets the International Classification of Headache Disorders(ICHD) criteria
* Frequency: Headache frequency based upon prospective headache diary of 28 days must be ≥ 4 and ≤ 28.
* PedMIDAS: PedMIDAS Disability Score \> 4, indicating at least mild disruption in daily activities and \< 140, indicating extreme disability that may require more comprehensive, multi-component therapy
* Use of one or more of the following prescribed nutraceuticals and/or preventive anti-migraine medications at the time or randomization or be on a stable dose of one or more of the following throughout the 12 weeks of the study \[Vitamin B2 (Riboflavin), Co-Q 10 (Coenzyme Q10), Magnesium (Mg), Vitamin D2 or D3 (Erocalciferol/Cholecalciferol), Depakote (Divalproate), Inderal (Propanerol), Elavil ((Amitripyline), Topamax (Topiramate), Periactin (Cyproheptadine)\]
* Language: English speaking, able to complete interviews and questionnaires in English
Exclusion Criteria:
* Continuous migraine defined as unrelenting headache for a 28 day period
* Must agree not to take non-specific acute medication, such as NSAIDS (e.g., ibuprofen), more than 3 times per week, or migraine specific acute medications, such as triptans, more than 6 times per month (to prevent medication overuse headache)
* PedMIDAS Disability Score \> 140, indicating extreme disability that may require more comprehensive, multi-component therapy
* Youth who are pregnant, or those who are sexually active and not using a medically accepted form of contraception (barrier or hormonal methods)
* Present severe psychiatric disease, alcohol or drug dependence, or documented developmental delays or impairments (e.g., autism, cerebral palsy, or mental retardation) or other circumstances, that, in the opinion of the investigator, would interfere with adherence to study requirements or safe participation in the study BEHAVIORAL: 40 minute session, BEHAVIORAL: 20 minute session, BEHAVIORAL: home practice e-health, BEHAVIORAL: home practice handout, BEHAVIORAL: phone call
Headache, Headache Disorders, Headache, Migraine, Migraine, Migraine Disorders, Migraine With Aura, Migraine Without Aura, Chronic Migraine
headache, migraine, cognitive behavioral therapy, pediatrics, mind body intervention, diaphragmatic breathing, progressive muscle relaxation, imagery, relaxation, biofeedback
A Phase 1b, Open-Label Study of DISC-3405 in Participants With Sickle Cell Disease (SCD)
Kara McClure - kara.mcClure@cchmc.org
ALL
18 years and over
PHASE1
NCT07187973
Inclusion Criteria:
• Aged 18 years or older at the time of signing the informed consent form (ICF).
• Male or female study participants with SCD HbSC or HbSS.
• Participants who have been diagnosed with any of the following SCD-related complications: between 1-10 episodes of VOC in the past 12 months, any history of sickle cell related retinopathy, silent cerebral infarct, avascular necrosis, sensorineural hearing loss; or at least 1 episode of priapism, hepatic sequestration, splenic sequestration, or splenic infarct within the last 12 months as assessed locally.
• Hgb ≥7.0 g/dL during Screening. The first 2 participants must have an Hgb ≥9 g/dL.
• Normal alpha globin gene screen.
• Absolute reticulocyte count or % reticulocyte count \>1.5 × upper limit of normal (ULN) during Screening.
• TSAT ≥15% at Screening.
• Ferritin ≥50 ng/mL for HbSC or ≥100 ng/mL for HbSS (ferritin must be \<1000 ng/mL at Screening).
• For participants taking hydroxyurea, L-glutamine, or crizanlizumab, stable dose for at least 2 months prior to Screening and with no anticipated need for dose adjustments during the study.
• If male, not vasectomized for at least 6 months, with female sexual partner(s) of childbearing potential, agrees he and partner will use double methods of the following highly effective methods of birth control (described below) from the first dose of randomized study drug until 120 days after the last administration of study drug and must not donate sperm during their study participation:
• Stable hormonal contraceptive (≥3 months; female partner) in conjunction with a barrier method (eg, condom \[male or female\] or diaphragm).
• Intrauterine device, in place for at least 3 months (female partner) in conjunction with a barrier method (eg, condom \[male or female\] or diaphragm).
• Surgically sterile by hysterectomy, bilateral oophorectomy, or bilateral tubal ligation (female partner) in conjunction with a barrier method (eg, condom \[male or female\] or diaphragm).
• If female, then EITHER postmenopausal, defined as at least 12 months natural, spontaneous amenorrhea, 6 months of spontaneous amenorrhea with serum follicle-stimulating hormone (FSH) \>40 mIU/mL at Screening, or at least 6 weeks following surgical menopause (bilateral oophorectomy with or without hysterectomy); surgically sterile, OR agree to use 1 of the following highly effective methods of birth control on Day 1 (or earlier) and for at least 120 days after the last administration of study drug:
• Stable hormonal contraceptive (≥3 months) in conjunction with a barrier method (eg, condom \[male or female\] or diaphragm).
• Intrauterine device, in place for at least 3 months in conjunction with a barrier method (eg, condom \[male or female\] or diaphragm).
• Tubal ligation or single male partner with vasectomy in conjunction with a barrier method (eg, condom \[male or female\] or diaphragm).
• Negative pregnancy test (females of childbearing potential) prior to dosing.
• Able to understand the study aims, procedures, and requirements, and provide written informed consent.
• Able to comply with all study procedures.
Exclusion Criteria:
• Participants who are receiving regularly scheduled blood (RBC) transfusion therapy or phlebotomy or have received RBC transfusion or phlebotomy within 60 days of Screening.
• Hospitalized for VOC or other sickle cell related complication within 14 days of Screening.
• Participants with clinically significant bacterial, fungal, parasitic, or viral infection.
• Active HIV, hepatitis B, or C. A positive hepatitis or HIV result should be discussed between the Investigator and Sponsor prior to enrollment.
• Significant renal dysfunction, evidenced by estimated glomerular filtration rate of \<60 mL/min/1.73 m2 at the Screening visit, as assessed locally.
• Hepatic dysfunction characterized by alanine aminotransferase (ALT) \>2.5 × ULN.
• Any episode of ACS in the last 6 months.
• Prior or planned hematopoietic stem cell transplant or gene therapy.
• History of unstable or deteriorating cardiac or pulmonary disease within 6 months prior to Screening.
• History of invasive malignancies within the last 5 years, except localized cured prostate cancer and cervical cancer, or other malignancies deemed acceptable by the Sponsor.
• Major surgery within 8 weeks before Screening or incomplete recovery from any previous surgery.
• A history or known allergic reaction to any IP excipients or history of anaphylaxis to any food or drug.
• History of alcohol dependence or excessive alcohol consumption, as assessed by the Investigator.
• Other medical or psychiatric condition or laboratory finding not specifically noted above that, in the judgment of the Investigator or Sponsor, would put the participant at an unacceptable risk or otherwise preclude the participant from participating in the study.
• Condition or concomitant medication that would confound the ability to interpret clinical, clinical laboratory, including a major psychiatric condition that has had an exacerbation or required hospitalization in the last 6 months.
• If female, pregnant or breastfeeding.
• Participation in any other clinical protocol or investigational study that involves administration of experimental therapy and/or therapeutic devices within 30 days of Screening.
• Participants with a history of transient ischemic attack or stroke may be considered in consultation with Sponsor.
DRUG: DISC-3405
Sickle Cell Disease
Efficacy and Safety Study of Rimegepant for the Preventative Treatment of Migraine in Pediatric Subjects
Michelle Shin - michelle.shin@cchmc.org
ALL
6 years to 17 years old
PHASE3
NCT05156398
Inclusion Criteria:
• Subject has at least a 6 month history of migraine (with or without aura) and including the following:
• 14 or less headache days per month during the 3 month period prior to the Screening Visit
• 6 or more migraine days during the Observation Period
• 14 or less headache days during the Observation Period
• Pediatric Migraine Disability Assessment Scale (PedMIDAS) Disability Score of \>10 to ≤50, indicating mild (score of 11 to 30) or moderate (score of 31 to 50) disruption in daily activities, as assessed at the Baseline (Randomization) Visit
• Ability to verbally distinguish migraine attacks from tension/cluster or other types of headaches
• Migraine attacks, on average, lasting 4 - 72 hours if untreated
• Subjects on prophylactic migraine medication are permitted to remain on therapy if the dose has been stable for at least 3 months (12 weeks) prior to the Screening Phase, and the dose is not expected to change during the course of the study. 2) Male and female subjects ≥ 6 to \<18 years; subjects must be less than 18 at the time of signing assent / consent. 3)Subjects must have a weight of ≥40 kg (child cohort requirement ≥15 kg) at the Screening Visit.
Exclusion Criteria:
• Subjects with a history of basilar migraine, cluster headaches, or hemiplegic migraine
• The subject has a continuous migraine (defined as an unrelenting headache) within 1 month prior to Screening Visit.
• The subject has a history or diagnosis of complications of migraine
• The subject has a confounding and clinically significant pain syndrome that may interfere with the subject's ability to participate in this study.
• The subject has any current psychiatric condition that is uncontrolled and/or untreated for a minimum of 6 months prior to the Screening Visit. Subjects with a lifetime history of psychosis and/or mania are excluded.
• History of suicidal behavior or the subject is at risk of self-harm or harm to others.
• History of major psychiatric disorder.
• The subject has a current diagnosis or history of substance abuse
• The subject has a history of moderate or severe head trauma or other neurological disorder (including seizure disorder) or systemic medical disease that is, in the investigator's opinion, likely to affect central nervous system functioning.
DRUG: Rimegepant, DRUG: Placebo
Migraine
Migraine, Migraine prevention, Phonophobia, Photophobia, Nausea, Pediatric migraine, Adolescent migraine
Study to Evaluate Sotatercept (MK-7962) in Children With Pulmonary Arterial Hypertension (PAH) (MK-7962-008) (MOONBEAM)
Jaynee Bartsch - jaynee.bartsch@cchmc.org
ALL
1 year to 17 years old
PHASE2
NCT05587712
Inclusion Criteria
* Documented, historic diagnostic right heart catheterization (RHC) any time before Screening confirming the diagnosis of PAH WHO Group 1 in any of the following subtypes:
* Idiopathic pulmonary arterial hypertension (IPAH)
* Heritable PAH
* Drug/toxin-induced PAH
* PAH associated with connective tissue disease
* PAH-congenital heart disease (CHD) with shunt closure \>6 months before Screening and subsequently confirmed by RHC before Screening
* PAH with coincidental shunt.
* Must be on a stable dose(s) of background PAH therapy (phosphdiesterase-5 (PDE5) inhibitors, endothelin receptor antagonists (ERAs), soluble guanylate cyclase stimulators (sGCS), or prostanoids \[including subcutaneous and intravenous\])
* If male, agree to the following during the intervention period and for at least 16 weeks (112 days) after the last dose of study intervention:
* Abstains from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agrees to remain abstinent or
* Uses contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause, documented from the site personnel's review of the participant's medical records, medical examination, or medical history interview) as detailed below:
* Uses a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a woman of childbearing potential (WOCBP) who is not currently pregnant Note: Men with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse or use a male condom during each episode of penile-vaginal penetration.
* If female, must be either not a WOCBP or use a contraceptive method that is highly effective or be abstinent from heterosexual intercourse during the intervention period and for at least 16 weeks (112 days) after the last dose of study intervention
* If male, agrees to refrain from donating blood or sperm for the duration of the study and for 16 weeks (112 days) after the last dose of study intervention
* If female, agrees to refrain from donating blood, eggs, or ovum for the duration of the study and for at least 16 weeks (112 days) after the last dose of study intervention
Exclusion Criteria
* History of left-sided heart disease, including valvular disease (eg, moderate or greater mitral or aortic regurgitation or stenosis), left ventricular outflow tract obstruction, and/or left heart failure (eg, restrictive or dilated cardiomyopathy)
* Severe (as based on the opinion of the investigator) congenital or developmental abnormalities of the lung, thorax, and/or diaphragm
* History of Eisenmenger syndrome, Potts shunt, or atrial septostomy
* Unrepaired or residual cardiac shunt
* Diagnosis of pulmonary veno-occlusive diseases, pulmonary capillary hemangiomatosis, or overt signs of capillary and/or venous involvement
* PAH associated with portal hypertension
* Known visceral (lung, liver, or brain) arteriovenous malformation(s)
* History of full or partial pneumonectomy
* Untreated more than mild obstructive sleep apnea
* History of known pericardial constriction
* Family history of sudden cardiac death or long QT syndrome
* Any current or prior history of symptomatic coronary disease (myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft surgery, or cardiac anginal chest pain) within 6 months before Screening
* Cerebrovascular accident within 3 months before Screening
* Prior exposure to sotatercept or luspatercept or has had an allergic reaction to any of their excipients
DRUG: Sotatercept
Pulmonary Arterial Hypertension
Effectiveness of Nontraditional Hydroxyurea Algorithms: Novel and Clinical Evaluations (ENHANCE) (ENHANCE)
Charles T. Quinn, M.D., M.S. - charles.quinn@cchmc.org
ALL
6 month(s) and over
PHASE4
NCT07177300
Inclusion Criteria:
* Diagnosis of sickle cell anemia (HbSS) or sickle-β0-thalassemia (HbSβ0)
* Age 6 months at the time of enrollment
* Clinical decision by patient, family, and healthcare provider to initiate hydroxyurea therapy
Exclusion Criteria:
* Current treatment with regularly scheduled blood transfusions
* Sickle-hemoglobin C disease (HbSC), sickle-β+-thalassemia (HbSβ+) DRUG: PK-optimized oral hydroxyurea at MTD until 15 years of age.
Sickle Cell Anemia (HbSS), Sickle-β0-thalassemia (HbSβ0)
sickle cell anemia, SCD, sickle cell, hydroxyurea