DFMO as Maintenance Therapy for Molecular High/Very High Risk and Relapsed Medulloblastoma
Purpose
Difluoromethylornithine (DFMO) will be used in an open label, multicenter, study as Maintenance Therapy for Molecular High Risk/Very High Risk and Relapsed/Refractory Medulloblastoma.
Condition
- Medulloblastoma
Eligibility
- Eligible Ages
- Under 21 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- 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
- 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.
Study Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- N/A
- Intervention Model
- Single Group Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Difluoromethylornithine (DFMO) |
study subjects will receive 730 Days of oral difluoromethylornithine (DFMO) at a dose of 2500 mg/m2 BID on each day of study. |
|
Recruiting Locations
Kentucky Children's Hospital
Lexington 4297983, Kentucky 6254925 40502
Lexington 4297983, Kentucky 6254925 40502
Arkansas Children's Hospital
Little Rock 4119403, Arkansas 4099753 72202
Little Rock 4119403, Arkansas 4099753 72202
UCSF Benioff Children's Hospital Oakland
Oakland 5378538, California 5332921 94609
Oakland 5378538, California 5332921 94609
Rady Children's Hospital
San Diego 5391811, California 5332921 92123
San Diego 5391811, California 5332921 92123
Stanford University
Stanford 5398563, California 5332921 94305
Stanford 5398563, California 5332921 94305
Nicklaus Children's Hospital
Miami 4164138, Florida 4155751 33155
Miami 4164138, Florida 4155751 33155
Arnold Palmer Hospital for Children
Orlando 4167147, Florida 4155751 32806
Orlando 4167147, Florida 4155751 32806
All Children's Hospital Johns Hopkins Medicine
St. Petersburg 4171563, Florida 4155751 33701
St. Petersburg 4171563, Florida 4155751 33701
St. Joseph's Children's Hospital
Tampa 4174757, Florida 4155751 33607
Tampa 4174757, Florida 4155751 33607
Kapiolani Medical Center for Women and Children
Honolulu 5856195, Hawaii 5855797 96813
Honolulu 5856195, Hawaii 5855797 96813
Advocate Aurora Research Institute
Chicago 4887398, Illinois 4896861 60453
Chicago 4887398, Illinois 4896861 60453
Norton Children's Research Institute/Affiliated with University of Louisville School of Medicine
Louisville 4299276, Kentucky 6254925 40202
Louisville 4299276, Kentucky 6254925 40202
Contact:
Jennifer Miller
Jennifer Miller
Children's Mercy Hospitals and Clinics
Kansas City 4393217, Missouri 4398678 64108
Kansas City 4393217, Missouri 4398678 64108
Cardinal Glennon Children's Medical Center
St Louis 4407066, Missouri 4398678 63104
St Louis 4407066, Missouri 4398678 63104
Hackensack University Medical Center
Hackensack 5098706, New Jersey 5101760 07601
Hackensack 5098706, New Jersey 5101760 07601
Levine Children's Hospital
Charlotte 4460243, North Carolina 4482348 28204
Charlotte 4460243, North Carolina 4482348 28204
Randall Children's Hospital
Portland 5746545, Oregon 5744337 97227
Portland 5746545, Oregon 5744337 97227
Penn State Milton S. Hershey Medical Center and Children's Hospital
Hershey 5193342, Pennsylvania 6254927 17033
Hershey 5193342, Pennsylvania 6254927 17033
Hasbro Children's Hospital
Providence 5224151, Rhode Island 5224323 02903
Providence 5224151, Rhode Island 5224323 02903
Medical University of South Carolina
Charleston 4574324, South Carolina 4597040 29425
Charleston 4574324, South Carolina 4597040 29425
Dell Children's Blood and Cancer Center
Austin 4671654, Texas 4736286 78723
Austin 4671654, Texas 4736286 78723
More Details
- NCT ID
- NCT04696029
- Status
- Recruiting
- Sponsor
- Giselle Sholler
Detailed Description
In this study subjects will receive 730 Days of oral difluoromethylornithine (DFMO) at a dose of 2500 mg/m2 BID on each day of study. Subjects will be evaluated in 3 Cohorts: Cohort 1: Molecular High Risk Medulloblastoma Cohort 2: Molecular Very High Risk Medulloblastoma Cohort 3: Relapsed/Refractory Medulloblastoma A total of 118 subjects across all cohorts will be enrolled to ensure that there will be 107 evaluable subjects (32-39 per cohort)