Phase II Trial of Eflornithine/DFMO as Maintenance Therapy for Molecular High Risk/Very High Risk and Relapsed/Refractory Medulloblastoma

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.