Inclusion Criteria:

          1. Age: 0-21 years of age at diagnosis

          2. Pathology All patients must either have a pathologically confirmed diagnosis of
             medulloblastoma with molecular grouping identified by either Nanostring or methylation
             profiling.

             Cohort 1- Molecular High Risk:

               -  Metastatic non-MYC amplified Group 3

               -  Metastatic Group 4

               -  Metastatic non-WNT/non-SHH (Must be non-MYC amplified)

             Cohort 2- Molecular Very High Risk

               -  Metastatic OR MYCN amplified OR TP53 mutant non-infant (>3 yrs) SHH

               -  MYC amplified Group 3

               -  Non-WNT, non-SHH infant (< 3 yrs)

             Cohort 3: Relapsed/Refractory Medulloblastoma

          3. Pre-enrollment tumor survey:

             Prior to enrollment on this study, a determination of mandatory disease staging must
             be performed:

               -  Tumor imaging studies including: Brain and spine MRI

               -  Lumbar Puncture only if previously positive

               -  Bone Marrow aspiration/biopsy only if previously positive

               -  This disease assessment is required for eligibility and preferably should be done
                  within 2 weeks prior to first dose of study drug, but must be done within a
                  maximum of 4 weeks before first dose of study drug.

          4. Disease Status: Subjects must have no evidence of disease, or stable* residual
             nonbulky** disease.

             *Stable residual disease defined as non-progression over 2 separate imaging studies at
             least 6 weeks apart

             **Non-bulky disease defined as maximal cross-sectional area < 3cm^2 at enrollment.
             Patients with leptomeningeal disease are allowed to participate on study.

          5. Timing from prior therapy:

             Enrollment (first dose of DFMO) no later than 60 days after last dose of conventional
             chemotherapy. Patients who have undergone high dose chemotherapy (HDCT) with
             autologous stem cell transplantation (SCT) are eligible if more than 45 days have
             elapsed since date of last SCT.

          6. Patients must have a Lansky or Karnofsky Performance Scale score of ≥ 50% (see
             Appendix II) and patients must have a life expectancy of ≥ 2 months.

          7. All clinical and laboratory studies for organ functions to determine eligibility must
             be performed within 7 days prior to first dose of study drug unless otherwise
             indicated below.

          8. Patients must have adequate organ functions at the time of registration:

               -  Hematological: Hematological recovery as defined by ANC ≥750/μL, platelets ≥30
                  (non-transfused x 7 days)

               -  Liver: Adequate liver function as defined by AST and ALT <10x upper limit of
                  normal

               -  Renal: Adequate renal function defined as (perform one of the following):
                  Creatinine clearance or radioisotope GFR ≥ 70 mL/min/1.73 m2 or a serum
                  creatinine based on age/gender

          9. Females of childbearing potential must have a negative pregnancy test. Patients of
             childbearing potential must agree to use an effective birth control method. Female
             patients who are lactating must agree to stop breast-feeding.

         10. Written informed consent in accordance with institutional and FDA guidelines must be
             obtained from all subjects (or patients' legal representative).

        Exclusion Criteria:

          1. BSA of <0.25 m2

          2. Metastatic disease outside of CNS

          3. Relapsed/refractory patients who are radiation-naïve and age 5 years or older at time
             of enrollment

          4. Investigational Drugs: Subjects who are currently receiving another investigational
             drug are excluded from participation.

          5. Anti-cancer Agents: Subjects who are currently receiving other anticancer agents are
             not eligible. Subjects must have fully recovered from the hematological and bone
             marrow suppression effects of prior chemotherapy.

          6. Infection: Subjects who have an uncontrolled infection are not eligible until the
             infection is judged to be well controlled in the opinion of the investigator.

          7. Subjects who, in the opinion of the investigator, may not be able to comply with the
             safety monitoring requirements of the study, or in whom compliance is likely to be
             suboptimal, should be excluded.