Molecular and Clinical Risk-Directed Therapy for Infants and Young Children With Newly Diagnosed Medulloblastoma

The film gives the main points. The full list below is copied from the registry; the study team makes the final decision.

• AgeNo minimum to 59 Months
• SexAll
• Healthy volunteersNo

You may be able to join if

• Inclusion Criteria - Screening Phase (All Patients)
• Participants with presumptive/suspected newly diagnosed medulloblastoma.
• Participant meets one of the following criteria at the time of screening:
• Age < 36 months OR Age ≥ 36 months and < 60 months with presumptive/suspected non-metastatic disease
• Participant must have adequate tumor tissue from primary tumor for central review of pathology and molecular classification by methylation and IHC
• Participant must be able to begin treatment as outlined in the protocol within 36 days of definitive surgery (day of surgery is Day 0). In case a second surgery is clinically indicated to remove the residual tumor prior to starting treatment, the second surgery will be considered as the definitive surgery (Day 0).
• Parent or legal guardian can understand and is willing to sign a written informed consent document according to institutional guidelines.
• Exclusion Criteria - Screening Phase
• Participants with other clinically significant medical disorders (i.e., serious infections or significant cardiac, pulmonary, hepatic, psychiatric, or other organ dysfunction) that could compromise their ability to tolerate protocol therapy or would interfere with the study procedure.
• Inclusion Criteria - Study Enrollment (All Patients)
• Participant must be < 60 months of age at time of enrollment.
• Note: Each treatment stratum has additional specific age requirements
• Participant must have confirmation of newly diagnosed medulloblastoma per Central Review:
• Central review includes histopathology, IHC and St. Jude Clinical Genomic Methylation Profiling conducted on MLPNet. If tissue or the extracted DNA does not meet quality control criteria for methylation analysis or if methylation classifier is unable assign molecular group/subgroup within the assigned classifier (MLPNet) parameters, then IHC will be used to define molecular group of these cases. IHC cannot be used to determine molecular subgroup. Therefore, IHC defined SHH patients will be enrolled on Stratum S-1 under "SHH-NOS", and all NWNS and indeterminate molecular group will be enrolled on stratum N.
• Note: Diagnosis of medulloblastoma, as well as group and subgroup assignment, will be done by central pathology review at St. Jude only. No outside testing is allowed for trial enrollment.
• Participant must have disease staged by MRI of the brain and spine and by cytologic examination of CSF* and be placed into the following categories:
• M0: no evidence of metastatic disease.
• must include a negative CSF cytology result
• M1: Tumor cells found in the CSF but no other evidence of metastasis
• M2: Intracranial tumor beyond the primary tumor site
• M3: Metastatic disease in the spine
• M4: Extraneural metastatic disease
• *All participants are to undergo CSF cytologic examination regardless of presence or absence of gross metastatic disease unless procedure is medically contraindicated. CSF is to be obtained by lumbar puncture (LP) performed at least 10 days after surgery. If LP is medically contraindicated, ventricular CSF from a shunt or Ommaya reservoir may be used for staging but this is not the preferred option due to lower sensitivity. If LP is medically contraindicated and the patient doesn't have a shunt or reservoir for CSF sampling, the treating physician should reach out to PI or Co-PI regarding decision on enrollment to SJiMB21. The decision to enroll without CSF cytology will be made on case-by-case basis.
• Note: Participants who have M2 disease and positive CSF will be assigned to M3.
• Note: Participants will be assigned to the highest stage number for which they meet eligibility.
• Note: Treatment stratums may have additional stage requirements.
• Patient must have received no previous radiotherapy, chemotherapy, or other brain tumor-directed therapy other than corticosteroid therapy and surgery.
• Participant must have a Lansky performance score of > 30 (except for patients with posterior fossa syndrome.
• Participant must have adequate organ function prior to study entry, as defined by:
• Absolute neutrophil counts (ANC) >750/mm^3
• Platelet count ≥ 50,000/mm^3 without support of a platelet transfusion within 7 days
• Hemoglobin ≥8.0 g/dL (with or without support of a blood transfusion).
• Normal liver function as defined by Alanine aminotransferase (ALT) concentration ≤ 3 x 45 U/L and total bilirubin ≤ 3 x 1.0.
• Adequate renal function as defined by a serum creatinine concentration:
• Age - 0 to <1year; Maximum Serum Creatinine (mg/dl) - Male 0.5; Female 0.5
• Age - 1 to < 2years; Maximum Serum Creatinine (mg/dl) - Male 0.6; Female 0.6
• Age - 1 to < 2yearsr; Maximum Serum Creatinine (mg/dl) - Male 0.8; Female 0.8
• Participant's parent or legal guardian has the ability to understand and the willingness to sign a written informed consent document according to institutional guidelines.
• Inclusion Criteria - Stratum S-2
• Participant must have confirmed diagnosis of the following medulloblastoma molecular group and subgroup per Central Review.
• Medulloblastoma SHH-2
• Participant must meet one of the following criteria at time of enrollment:
• Age <36 months OR Age ≥ 36 months and < 60 months with non-metastatic disease (M0) Inclusion Criteria - Stratum S-1
• Participant must have confirmed diagnosis of one of the following medulloblastoma molecular subgroups per Central Review.
• Medulloblastoma SHH-1
• Medulloblastoma SHH-3
• Medulloblastoma SHH-4
• Medulloblastoma SHH-NOS
• Includes medulloblastoma cases that could not be assigned to a molecular subgroup using the DNA methylation classifier, but which are in the SHH group and/or cases defined as SHH by IHC.
• Participant must be < 36 months of age at time of enrollment
• Note: Patients who are < 36 months of age, regardless of metastatic status (M0/M+), are eligible for enrollment on stratum S-1.
• Inclusion Criteria - Stratum N
• Participant must have confirmed diagnosis of one of the following medulloblastoma molecular subgroups per Central Review.
• Medulloblastoma G3
• Medulloblastoma G4
• Medulloblastoma - Not classified into SHH (i.e., NWNS or indeterminate)
• Includes medulloblastoma cases that could not be assigned to a molecular group using the DNA methylation classifier but which are in the NWNS class and/or defined as NWNS by IHC.
• Participant must be <36 months of age at time of enrollment
• All NWNS patients (M+ and M0) are eligible for enrollment in stratum N
• Exclusion Criteria - All Patients
• CNS embryonal tumor other than medulloblastoma, for example, patients with diagnosis of Atypical Teratoid/Rhabdoid Tumor (ATRT), PNET, Pineoblastoma, Ependymoma, and ETMR are excluded.
• Participant with prior treatment for medulloblastoma, including:
• Radiotherapy
• Chemotherapy
• Cancer directed immunotherapy
• Targeted agents
• NOTE: Corticosteroid therapy is acceptable; prior treatment with chemotherapy, immunotherapy or targeted agents for non-cancer directed indications are acceptable as long as these have been stopped at least 14 days prior to start of therapy or 2 half-lives from last dose. (i.e., methotrexate for juvenile rheumatoid arthritis, JAK inhibitor therapy for eczema, etc.)
• Participant who is actively receiving any other investigational agents.
• Participant with other clinically significant medical disorders (i.e., serious infections or significant cardiac, pulmonary, hepatic, psychiatric, or other organ dysfunction) that could compromise their ability to tolerate protocol therapy or would interfere with the study procedures or results.

This is how the treatment is meant to work. Whether it helps, and how safe it is, is what this trial is testing.

dichloromethotrexate. A chlorinated methotrexate derivative. Dichloromethotrexate inhibits the enzyme dihydrofolate reductase, thereby preventing the synthesis of purine nucleotides and thymidylates and inhibiting DNA and RNA synthesis. This agent is metabolized and excreted by the liver. NCI Drug Dictionary

Treatments listed in the registry

• Surgical resection (Procedure): All participants enrolled will undergo surgical resection prior to treatment. The maximal resection that can be achieved without undue risk to the patient will be attempted, with decisions about feasibility and extent of resection left to the discretion of the neurosurgeon. In instances where an STR is the best extent of resection achieved prior to start of therapy, a "second-look" surgery may be performed between cycles of chemotherapy after discussion with the principal investigator.
• Ommaya/VPS (Procedure): All participants enrolled on S-1 will undergo
• Methotrexate (Drug): Route of administration: Intravenously (IV)
• Cisplatin (Drug): Route of administration: Intravenously (IV)
• Vincristine (Drug): Route of administration: Intravenously (IV)
• Cyclophosphamide (Drug): Route of administration: Intravenously (IV)
• Carboplatin (Drug): Route of administration: Intravenously (IV)
• Topotecan (Drug): Route of administration: Intravenously (IV)
• Etoposide (Drug): Route of administration: Intravenously (IV)
• Pegfilgrastim (Drug): Route of administration: subcutaneous (SQ)
• Filgrastim (Drug): Route of administration: subcutaneous (SQ) or Intravenously (IV)
• Irradiation (Radiation): All participants in stratum N will undergo craniospinal irradiation (CSI) with boost to the primary tumor site once they reach 36 months of age. The dose given is based on the molecular risk group and disease response to chemotherapy as noted in the arm descriptions. The type of radiation used includes conformal radiation therapy (photons) or intensity modulated radiation therapy (IMRT) or proton beam therapy.
• Educational and Media Intervention (Other): Participants watch a 75-minute caregiver education video program and receive access to interactive games on a smartphone or tablet throughout the optional cognitive study.
• SOC, Educational and Media Intervention (Other): Standard-of-care (SOC) treatment during main cognitive study. After the one-year serial cognitive evaluation, participants will be offered participation in the cognitive study group I intervention.
• Methotrexate (Drug): Route of administration: Intravenously (IV) & Intra Ventricular (IVT)

Non Randomized · Parallel · masking: None

As the registry describes them. Requirements to join, such as a tissue sample, are in the eligibility list above even when on-study procedures are optional. Ask the study team which steps apply to you.

• surgery: Part of the study plan
• radiation: Part of the study plan

Main goals

• Progression free survival of SHH-2 infant (0-2.99 years) and young child (3-4.99 years) medulloblastoma patients treated with systemic HD-MTX-based chemotherapy only. (Up to 7 years after enrollment with PFS estimation occurring 2 years after treatment initiation of last patient)
• Progression free survival of SHH-1 infant (0-2.99 years) medulloblastoma patients treated with systemic HD-MTX-based chemotherapy augmented with IVT-MTX. (Up to 7 years after enrollment with PFS estimation occurring 2 years after treatment initiation of last patient)
• Progression free survival of G3/G4 infant (0-2.99 years) medulloblastoma patients treated with systemic chemotherapy and delayed risk-adapted CSI augmented with carboplatin. (Up to 7 years after enrollment with PFS estimation occurring 2 years after treatment initiation of last patient)
• IQ among infants and young children treated with systemic chemotherapy only compared to patients treated with systemic chemotherapy and intra-ventricular chemotherapy or delayed risk-adapted craniospinal irradiation (Baseline through 5 years after enrollment)
• Executive function among infants and young children treated with systemic chemotherapy only compared to patients treated with systemic chemotherapy and intra-ventricular chemotherapy or delayed risk-adapted craniospinal irradiation (Baseline through 5 years after enrollment)
• Health-related quality of life among infants and young children treated with systemic chemotherapy only compared to patients treated with systemic chemotherapy and intra-ventricular chemotherapy or delayed risk-adapted craniospinal irradiation (Baseline through 5 years after enrollment)

Other goals

• Change in IQ among infants (0-2.99 years) and young children (3-4.99 years) treated for medulloblastoma
• Change in executive function among infants (0-2.99 years) and young children (3-4.99 years) treated for medulloblastoma
• Change in health-related quality of life among infants (0-2.99 years) and young children (3-4.99 years) treated for medulloblastoma
• Association of familial factors and environmental factors with socioeconomic status
• Association of familial factors and environmental factors with cognitive late effects.
• Evaluate family interest in caregiver education combined with interactive neurodevelopmental games.
• Evaluate intervention feasibility by measuring the rate of participants completing a caregiver education combined with interactive. neurodevelopmental games.
• Evaluate the acceptability of a caregiver education combined with interactive neurodevelopmental games.
• Magnitude of change in cognition and social-emotional development associated with a caregiver education program combined with interactive neurodevelopmental games.
• To characterize the plasma systemic clearance (CL) of cyclophosphamide (CTX) in infants and young children with medulloblastoma.
• To characterize the area under the concentration-time curve (AUC0-24h) of carboxyethylphosphoramide (CEPM) in infants and young children with medulloblastoma receiving cyclophosphamide.
• To characterize the area under the concentration-time curve (AUC0-24h) of 4-hydroxy-cyclophosphamide (4OHCTX) in infants and young children with medulloblastoma receiving cyclophosphamide.
• To assess potential covariates (e.g., demographics, clinical chemistry) explaining inter- and intra-patient variability in in the plasma systemic clearance (CL) of CTX in infants and young children with medulloblastoma receiving CTX.
• To assess potential covariates (e.g., demographics, clinical chemistry) explaining inter- and intra-patient variability in CEPM AUC0-24h in infants and young children with medulloblastoma receiving CTX.
• To assess potential covariates (e.g., demographics, clinical chemistry) explaining inter- and intra-patient variability in 4OHCTX AUC0-24h in infants and young children with medulloblastoma receiving CTX.
• To characterize the plasma systemic clearance (CL) of vincristine (VCR) in infants and young children with medulloblastoma.
• To assess potential covariates (e.g., demographics, clinical chemistry) explaining inter- and intra-patient variability in VCR PK parameter (CL) in infants and young children with medulloblastoma receiving VCR.
• To characterize the plasma systemic clearance (CL) of topotecan (TPT) in infants and young children with medulloblastoma.
• To assess potential covariates (e.g., demographics, clinical chemistry) explaining inter- and intra-patient variability in TPT PK parameter (CL) in infants and young children with medulloblastoma receiving TPT.
• To characterize the plasma systemic methotrexate (MTX) clearance (CL) in infants and young children with medulloblastoma.
• To characterize the area under the concentration-time curve (AUC0-24h) of 7-hydroxymethotrexate (7OHMTX) in infants and young children with medulloblastoma receiving methotrexate.
• To assess potential covariates (e.g., demographics, clinical chemistry) explaining inter- and intra-patient variability in MTX PK parameter CL in infants and young children with medulloblastoma receiving MTX.
• To assess potential covariates (e.g., demographics, clinical chemistry) explaining inter- and intra-patient variability in 7OHMTX PK parameter AUC0-24h in infants and young children with medulloblastoma receiving MTX.

Planned enrollment: 130 (estimated).

• Lucille Packard Children's Hospital Stanford, Palo Alto, California
• Orlando Health Arnold Palmer Hospital for Children, Orlando, Florida
• St. Joseph's Children's Hospital, Tampa, Florida
• C.S. MOTT Children's Hospital, University of Michigan, Ann Arbor, Michigan
• Children's Hospital and Clinics of Minnesota, Minneapolis, Minnesota
• St. Jude Children's Research Hospital, Memphis, Tennessee
• UT Southwestern Medical Center/Harold C Simmons Comprehensive Cancer Center, Dallas, Texas
• Cook Children's Medical Center, Fort Worth, Texas
• Texas Children's Hospital, Houston, Texas
• Primary Children's Hospital, Salt Lake City, Utah

Site status as of Oct 30, 2026. Check the live record before contacting a site.

• ClinicalTrials.gov NCT05535166
• NCI Drug Dictionary: C642

Registry record reviewed as fetched Oct 30, 2026, last updated by the sponsor Sep 14, 2026. Public record; not medical advice.