Reduced Craniospinal Radiation Therapy and Chemotherapy in Treating Younger Patients With Newly Diagnosed WNT-Driven Medulloblastoma

Inclusion Criteria:

   - Patients must be greater than or equal to 3 years and less than 22 years of age at the
   time of enrollment

   - Patients must be newly diagnosed and have:

      - Eligibility confirmed by rapid central pathology and molecular screening review
      on APEC14B1:

         - Classical histologic type (non LC/A) WNT medulloblastoma

         - Positive nuclear beta-catenin by immunohistochemistry (IHC)

         - Positive for CTNNB1 mutation by Sanger sequencing

         - Negative for MYC and MYCN by fluorescence in situ hybridization (FISH)

   - Patient must have negative lumbar cerebrospinal fluid (CSF) cytology

      - Note: CSF cytology for staging should be performed no sooner than 14 days post
      operatively to avoid false positive CSF; ideally, CSF should be obtained between
      day 14 and day 21 to allow for final staging status before enrollment onto the
      study; patients with positive CSF cytology obtained 0 to 14 days after surgery
      should have cytology repeated to determine eligibility and final CSF status;
      patients with negative CSF cytology from lumbar puncture obtained 0 to 14 days
      after surgery do not need cytology repeated; patients with negative CSF cytology
      from lumbar puncture obtained prior to surgery do not need cytology repeated
      post-operatively

   - Patients must have eligibility confirmed by Rapid Central Imaging Review on APEC14B1;
   patients must have =< 1.5 cm^2 maximal cross-sectional area of residual tumor; whole
   brain magnetic resonance imaging (MRI) with and without gadolinium and spine MRI with
   gadolinium must be performed

   - Patients must be enrolled, and protocol therapy must be projected to begin, no later
   than 36 days after definitive diagnostic surgery (day 0)

   - Peripheral absolute neutrophil count (ANC) >= 1000/uL

   - Platelet count >= 100,000/uL (transfusion independent)

   - Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions)

   - 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:

      - 3 to < 6 years of age: maximum (max) serum creatinine 0.8 mg/dL (males and
      females)

      - 6 to < 10 years of age: max serum creatinine 1 mg/dL (males and females)

      - 10 to < 13 years of age: max serum creatinine 1.2 mg/dL (males and females)

      - 13 to < 16 years of age: max serum creatinine 1.5 md/dL (males) and 1.4 md/dL
      (females)

      - >= 16 years of age: max serum creatinine 1.7 mg/dL (males) and 1.4 mg/dL
      (females)

         - The threshold creatinine values were derived from the Schwartz formula for
         estimating GFR utilizing child length and stature data published by the
         Centers for Disease Control and Prevention (CDC)

   - Total or direct bilirubin =< 1.5 x upper limit of normal (ULN) for age, and

   - Serum glutamate pyruvate (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L (3x ULN);
   for the purpose of this study, the ULN for SGPT is 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, a coma or on assisted ventilation at
      the time of study enrollment

   - Patients must have receptive and expressive language skills in English, French, or
   Spanish to complete the QoL and neurocognitive assessments; if a patient meets these
   criteria but the parent/guardian speaks a language other than English, French, or
   Spanish, the patient may still be enrolled and tested, and the parent-report measures
   should be omitted

   - All patients and/or their parents or legal guardians must sign a written informed
   consent; assent, when appropriate, will be obtained according to institutional
   guidelines

   - All institutional, Food and Drug Administration (FDA), and National Cancer Institute
   (NCI) requirements for human studies must be met

Exclusion Criteria:

   - Patients with metastatic disease by either MRI evaluation (brain and spine) or lumbar
   CSF cytology are not eligible; patients who are unable to undergo a lumbar puncture
   for assessment of CSF cytology are ineligible

   - Patients must not have received any prior radiation therapy or chemotherapy
   (tumor-directed therapy) other than surgical intervention and/or corticosteroids

   - Pregnancy and Breast Feeding

      - Female patients who are pregnant are ineligible due to risks of fetal and
      teratogenic adverse events as seen in animal/human studies

      - Lactating females are not eligible unless they have agreed not to breastfeed
      their infants

      - Female patients of childbearing potential are not eligible unless a negative
      pregnancy test result has been obtained

      - Sexually active patients of reproductive potential are not eligible unless they
      have agreed to use an effective contraceptive method for the duration of their
      study participation

   - Patients with a history of moderate to profound intellectual disability (i.e.,
   intelligence quotient [Q)]=< 55) are not eligible for enrollment; PLEASE NOTE:
   Children with a prior history of attention deficit hyperactivity disorder (ADHD) or a
   specific learning disability (e.g., dyslexia) are eligible for this study. Children
   with posterior fossa syndrome (also known as cerebellar mutism) are eligible for this
   study