DFMO as Maintenance Therapy for Molecular High/Very High Risk and Relapsed Medulloblastoma

April 24, 2026 updated by: Giselle Sholler

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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)

Study Type

Interventional

Enrollment (Estimated)

118

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Canada
  • United States
    • Arkansas
      • Little Rock, Arkansas, United States, 72202
        • Recruiting
        • Arkansas Children's Hospital
        • Principal Investigator:
          • Kevin Bielamowicz
        • Contact:
    • California
      • Oakland, California, United States, 94609
        • Recruiting
        • UCSF Benioff Children's Hospital Oakland
        • Contact:
        • Principal Investigator:
          • Caroline Hastings
      • San Diego, California, United States, 92123
        • Recruiting
        • Rady Children's Hospital
        • Principal Investigator:
          • William Roberts
        • Contact:
      • Stanford, California, United States, 94305
        • Recruiting
        • Stanford University
        • Contact:
        • Principal Investigator:
          • Raya Saab
    • Connecticut
      • Hartford, Connecticut, United States, 06106
    • Florida
      • Miami, Florida, United States, 33155
      • Orlando, Florida, United States, 32806
      • St. Petersburg, Florida, United States, 33701
        • Recruiting
        • All Children's Hospital Johns Hopkins Medicine
        • Contact:
        • Principal Investigator:
          • Jennifer Dean
      • Tampa, Florida, United States, 33607
        • Recruiting
        • St. Joseph's Children's Hospital
        • Contact:
        • Principal Investigator:
          • Don Eslin
    • Hawaii
      • Honolulu, Hawaii, United States, 96813
        • Recruiting
        • Kapiolani Medical Center for Women and Children
        • Principal Investigator:
          • Kelley Hutchins
        • Contact:
    • Illinois
      • Chicago, Illinois, United States, 60453
        • Recruiting
        • Advocate Aurora Research Institute
        • Contact:
        • Principal Investigator:
          • Rebecca McFall
    • Kentucky
      • Lexington, Kentucky, United States, 40502
        • Recruiting
        • Kentucky Children's Hospital
        • Contact:
        • Principal Investigator:
          • Tom Badgett
      • Louisville, Kentucky, United States, 40202
        • Recruiting
        • Norton Children's Research Institute/Affiliated with University of Louisville School of Medicine
        • Contact:
          • Jennifer Miller
        • Principal Investigator:
          • Mustafa Barbour
    • Missouri
      • Kansas City, Missouri, United States, 64108
        • Recruiting
        • Children's Mercy Hospitals and Clinics
        • Principal Investigator:
          • Kevin Ginn
        • Contact:
      • St Louis, Missouri, United States, 63104
        • Recruiting
        • Cardinal Glennon Children's Medical Center
        • Principal Investigator:
          • William Ferguson
        • Contact:
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Recruiting
        • Hackensack University Medical Center
        • Principal Investigator:
          • Derek Hanson
        • Contact:
    • North Carolina
      • Charlotte, North Carolina, United States, 28204
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Recruiting
        • University of Oklahoma
        • Principal Investigator:
          • Rene McNall-Knapp
        • Contact:
    • Oregon
      • Portland, Oregon, United States, 97227
        • Recruiting
        • Randall Children's Hospital
        • Contact:
        • Principal Investigator:
          • Jason Glover
    • Pennsylvania
      • Hershey, Pennsylvania, United States, 17033
    • Rhode Island
      • Providence, Rhode Island, United States, 02903
        • Recruiting
        • Hasbro Children's Hospital
        • Principal Investigator:
          • Bradley DeNardo
        • Contact:
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Recruiting
        • Medical University of South Carolina
        • Principal Investigator:
          • Jaqueline Kraveka
        • Contact:
    • Texas
      • Austin, Texas, United States, 78723
        • Recruiting
        • Dell Children's Blood and Cancer Center
        • Principal Investigator:
          • Virginia Harrod
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 17 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
Drug: Difluoromethylornithine

DFMO (difluoromethylornithine is an inhibitor of ornithine decarboxylase (ODC) designated chemically as 2-(difluoromethyl)-DL-ornithine monohydrochloride monohydrate.

The dosage form to be used in this study is provided as a convex tablet containing 192 mg eflornithine (equivalent to 250 mg of eflornithine HCl, monohydrate). The tablets are packaged and sealed in opaque white HDPE bottles, and each bottle contains 100 tablets. The DMFO tablets are supplied by USWorldMeds (USWM).

The tablets are to be stored at room temperature (20-250C).

Other Names:
  • DFMO
  • Eflornithine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants with event free survival (EFS) during study
Time Frame: 2 years plus 5 years follow up
o To evaluate the efficacy of difluoromethylornithine (DFMO) as a single agent in preventing relapse in patients with molecular high risk and very high risk medulloblastoma, and relapsed/refractory medulloblastoma based upon the 2-year progression-free survival rate (PFS) compared to relevant historical controls.
2 years plus 5 years follow up

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Length of time that participants experience Overall Survival (OS)
Time Frame: 7 years
o To evaluate the efficacy of difluoromethylornithine (DFMO) as a single agent in patients with molecular high risk and very high risk medulloblastoma, and relapsed/refractory medulloblastoma based upon overall survival
7 years
Determine the Overall Response Rate (ORR) of Participants using Modified RANO Criteria
Time Frame: 2 years
To evaluate the efficacy of difluoromethylornithine (DFMO) as a single agent in patients with molecular high risk and very high risk medulloblastoma, and relapsed/refractory medulloblastoma based upon Response Rate for patients with non-bulky residual disease present.
2 years
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Time Frame: 2 years plus 30 days
To develop a complete safety and tolerability profile of difluoromethylornithine (DFMO) in pediatric and young adult subjects with medulloblastoma.
2 years plus 30 days
Determine amount of DFMO in the CSF at 3 hours post dose
Time Frame: 2 years
o To measure CSF penetration after DFMO administration in pediatric subjects with medulloblastoma
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Giselle Sholler

Investigators

  • Study Chair: Michael A Huang, MD, Beat Childhood Cancer

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 29, 2021

Primary Completion (Estimated)

March 1, 2028

Study Completion (Estimated)

March 1, 2029

Study Registration Dates

First Submitted

January 4, 2021

First Submitted That Met QC Criteria

January 4, 2021

First Posted (Actual)

January 6, 2021

Study Record Updates

Last Update Posted (Actual)

April 28, 2026

Last Update Submitted That Met QC Criteria

April 24, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BCC016

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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