This study will evaluate the use of Difluoromethylornithine (DFMO) as a single agent in patients with high risk medulloblastoma after completing therapy as maintenance therapy with the hopes of preventing relapse. It will be used in an open label, single agent, multicenter, study for subjects with:
In this study subjects will receive 2 years of oral difluoromethylornithine (DFMO) at a dose of 2500 mg/m2 BID on each day of study.
Subjects will be evaluated in 3 Cohorts:
1. Age: 0-21 years of age at diagnosis
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:
Cohort 2- Molecular Very High Risk
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:
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:
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).
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.
Subjects willing to participate in the correlative biologic studies will sign an additional consent form to provide samples for analysis.
Contact Information: For more information about this study, contact Catherine Redinger at 501-364-4290 at RedingerCatherineL@uams.edu or Suzy Hall at 501-364-4181 at Hallsf@archildrens.org.