Neuroblastoma Maintenance Therapy Trial (NMTT)

April 4, 2024 updated by: Giselle Sholler

NMTT- Neuroblastoma Maintenance Therapy Trial Using Difluoromethylornithine (DFMO)

Difluoromethylornithine (DFMO) will be used in an open label, single agent, multicenter, study for patients with neuroblastoma in remission. In this study subjects will receive 730 Days of oral difluoromethylornithine (DFMO) at a dose of 750 mg/m2 ± 250 mg/m2 BID (strata 1, 2, 3, and 4) OR 2500 mg/m2 BID (stratum 1B) on each day of study. This study will focus on the use of DFMO in high risk neuroblastoma patients that are in remission as a strategy to prevent recurrence.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

258

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
    • Alabama
      • Birmingham, Alabama, United States
        • Recruiting
        • University of Alabama, Children's of Alabama
        • Principal Investigator:
          • Elizabeth Alva, MD
        • Contact:
    • Arkansas
      • Little Rock, Arkansas, United States, 72202
        • Recruiting
        • Arkansas Children's Hospital
        • Principal Investigator:
          • Kevin Bielamowicz, MD
        • Contact:
    • California
      • Oakland, California, United States
        • Recruiting
        • UCSF Benioff Children's Hospital Oakland-
        • Contact:
        • Principal Investigator:
          • Jennifer Michlitsch, MD
      • San Diego, California, United States, 92123
        • Recruiting
        • Rady Children's Hospital
        • Principal Investigator:
          • William Roberts, MD
        • Contact:
    • Colorado
      • Denver, Colorado, United States
    • Connecticut
      • Hartford, Connecticut, United States, 06106
        • Recruiting
        • Connecticut Children's Hospital
        • Principal Investigator:
          • Michael Isakoff, MD
        • Contact:
    • Florida
      • Gainesville, Florida, United States, 32611
        • Recruiting
        • University of Florida
        • Principal Investigator:
          • Joanne Lagmay, MD
        • Contact:
      • Orlando, Florida, United States, 32806
        • Recruiting
        • Arnold Palmer Hospital for Children
        • Principal Investigator:
          • Amy Smith, MD
        • Contact:
      • Saint Petersburg, Florida, United States, 33701
        • Recruiting
        • All Children's Hospital Johns Hopkins Medicine
        • Principal Investigator:
          • Jonathan Metts, MD
        • Contact:
      • Tampa, Florida, United States, 33614
        • Recruiting
        • St. Joseph's Children's Hospital
        • Principal Investigator:
          • Don Eslin, MD
        • Contact:
    • Georgia
      • Augusta, Georgia, United States
        • Recruiting
        • Augusta University Health
        • Contact:
        • Principal Investigator:
          • Coleen McDonough, MD
    • Hawaii
      • Honolulu, Hawaii, United States, 96813
        • Recruiting
        • Kapiolani Medical Center for Women and Children
        • Contact:
        • Principal Investigator:
          • Randal Wada, MD
    • Idaho
      • Boise, Idaho, United States
        • Recruiting
        • St. Lukes
        • Contact:
        • Principal Investigator:
          • Martha Pachecho, MD
    • Illinois
      • Chicago, Illinois, United States
        • Recruiting
        • Rebecca McFall
        • Contact:
        • Principal Investigator:
          • Rebecca McFall, MD
    • Kentucky
      • Lexington, Kentucky, United States
        • Recruiting
        • Kentucky Children's Hospital
        • Contact:
        • Principal Investigator:
          • Tom Badgett, MD
      • Louisville, Kentucky, United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02111
        • Completed
        • Tufts Medical Center
      • Worcester, Massachusetts, United States
        • Withdrawn
        • University of Massachusetts Medical School Worcester
    • Michigan
      • Grand Rapids, Michigan, United States, 49503
        • Recruiting
        • Helen DeVos Children's Hospital
        • Contact:
        • Principal Investigator:
          • David Hoogstra, MD
    • Minnesota
      • Minneapolis, Minnesota, United States, 55404
        • Recruiting
        • Children's Hospital and Clinics of Minnesota
        • Principal Investigator:
          • Jawhar Rawwas, MD
        • Contact:
    • Missouri
      • Kansas City, Missouri, United States, 64108
        • Recruiting
        • Children's Mercy Hospitals and Clinics
        • Contact:
        • Principal Investigator:
          • Kevin Ginn, MD
      • Saint Louis, Missouri, United States, 63104
        • Recruiting
        • Gina Martin
        • Principal Investigator:
          • William Ferguson, MD
        • Contact:
    • New Jersey
      • Hackensack, New Jersey, United States
        • Recruiting
        • Hackensack University Medical Center
        • Contact:
        • Principal Investigator:
          • Derek Hanson, MD
    • New York
      • New York, New York, United States
        • Recruiting
        • New York University
        • Contact:
        • Principal Investigator:
          • Sharon Gardner, MD
    • North Carolina
      • Charlotte, North Carolina, United States, 28204
        • Recruiting
        • Levine Children's Hospital
        • Contact:
        • Principal Investigator:
          • Thomas Russell, MD
      • Durham, North Carolina, United States
        • Recruiting
        • Duke University
        • Contact:
        • Principal Investigator:
          • Jessica Sun, MD
    • Ohio
      • Cleveland, Ohio, United States
        • Recruiting
        • Cleveland Clinic Children's
        • Contact:
        • Principal Investigator:
          • Stacey Zahler, MD
      • Columbus, Ohio, United States, 43205
        • Active, not recruiting
        • Nationwide Children's Hospital
    • Oregon
      • Portland, Oregon, United States
        • Recruiting
        • Randall Children's Hospital
        • Contact:
        • Principal Investigator:
          • Jason Glover, MD
    • Pennsylvania
      • Hershey, Pennsylvania, United States, 17033
        • Recruiting
        • Penn State Milton S. Hershey Medical Center and Children's Hospital
        • Contact:
        • Principal Investigator:
          • Valerie Brown, MD
    • Rhode Island
      • Providence, Rhode Island, United States
        • Recruiting
        • Hasbro Children's Hospital
        • Contact:
        • Principal Investigator:
          • Bradley DeNardo, MD
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Recruiting
        • Medical University of South Carolina
        • Principal Investigator:
          • Jaqueline Kraveka, MD
        • Contact:
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Recruiting
        • Monroe Carrell Jr. Children's Hospital at Vanderbilt
        • Principal Investigator:
          • Devang Pastakia, MD
        • Contact:
    • Texas
      • Austin, Texas, United States, 78723
      • Dallas, Texas, United States, 75235
        • Recruiting
        • Children's Medical Center
        • Principal Investigator:
          • Tanya Watt, MD
        • Contact:
      • Houston, Texas, United States, 77030
        • Recruiting
        • Texas Children's Cancer and Hematology Centers
        • Principal Investigator:
          • Jennifer Foster, MD
        • Contact:
    • Utah
      • Salt Lake City, Utah, United States, 84113
        • Recruiting
        • Primary Children's Hospital
        • Principal Investigator:
          • Matthew Dietz, MD
        • Contact:
    • Virginia
      • Norfolk, Virginia, United States
        • Recruiting
        • Children's Hospital of The King's Daughters
        • Contact:
        • Principal Investigator:
          • Eric Lowe, MD
      • Richmond, Virginia, United States
        • Recruiting
        • Virginia Commonwealth University
        • Principal Investigator:
          • Madhu Gowda, MD
        • Contact:
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Recruiting
        • Medical College of Wisconsin
        • Contact:
        • Principal Investigator:
          • Nathan Schloemer, MD

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

4 months to 28 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • All patients must have a pathologically confirmed diagnosis of neuroblastoma, < 30.99 years of age and classified as high risk at the time of diagnosis. Exception: patients who are initially diagnosed as non-high-risk neuroblastoma, but later converted (and/or relapsed) to high risk neuroblastoma are also eligible.

  • All patients must be in complete remission (CR):

    1. No evidence of residual disease on scan
    2. No evidence of disease metastatic to bone marrow.
  • Specific Criteria by Stratum:

Stratum 1/1B: All patients must have completed standard upfront therapy that replicates treatment which patients who were enrolled on ANBL0032 received, including:

intensive induction chemotherapy and (if feasible) resection of primary tumor, followed by: consolidation with high-dose chemotherapy with stem cell transplant and radiotherapy, followed by: immunotherapy with Ch14.18/IL-2/GM-CSF (dinutuximab) and retinoic acid;.

All subjects on Stratum 1/B must have also met the following criteria:

• A pre-transplant disease status evaluation that met International Neuroblastoma Response Criteria (INRC) for CR (complete response), VGPR (very good partial response), or PR (partial response) for primary site, soft tissue metastases and bone metastases. Patients who meet those criteria must also meet the protocol-specified criteria for bone marrow response prior to transplant as outlined below: No more than 10% tumor involvement (based on total nucleated cellular content) seen on any specimen from a bilateral bone marrow aspirate/biopsy.

Stratum 2: Neuroblastoma that is in first complete remission following standard upfront therapy different from that described for Stratum 1.

Stratum 3: Neuroblastoma that failed to have a response of at least PR following induction chemotherapy and surgical resection of the primary tumor, but that has achieved CR following additional therapy.

Stratum 4: Patients who have achieved a second or subsequent CR following relapse(s).

  • Pre-enrollment tumor survey: Prior to enrollment on this study, a determination of mandatory disease staging must be performed:

    • Tumor imaging studies including
    • Bilateral bone marrow aspirates and biopsy
    • This disease assessment is required for eligibility and preferably should be done within 2 weeks prior to enrollment, but must be done within a maximum of 4 weeks before enrollment.
  • Timing from prior therapy:

Stratum 1/1B: Enrollment no later than 60 days after completion of upfront therapy, (last dose of cis-retinoic acid) with a maximum of 6 cycles of cis-retinoic acid maintenance therapy.

Stratum 2, 3 and 4: Enrollment no later than 60 days from last dose of the most recent therapy.

  • Patients must have a Lansky or Karnofsky Performance Scale score of > 50% and patients must have a life expectancy of ≥ 2 months.
  • All clinical and laboratory studies for organ functions to determine eligibility must be performed within 7 days prior to enrollment unless otherwise indicated below.

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

    • Hematological: Total absolute phagocyte count ≥1000/μL
    • Liver: Subjects must have adequate liver function
    • Renal: Adequate renal function
  • 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.
  • Written informed consent in accordance with institutional and FDA (food and drug administration) guidelines must be obtained from all subjects (or patients' legal representative).

Exclusion Criteria:

  • BSA (Body Surface Area) of <0.25 m2.
  • Investigational Drugs: Subjects who are currently receiving another investigational drug are excluded from participation.
  • Anti-cancer Agents: Subjects who are currently receiving other anticancer agents are not eligible. Subjects must have fully recovered from hematological and bone marrow suppression effects of prior chemotherapy.
  • 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.
  • 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: Prevention
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Difluoromethylornithine (DFMO)
Subjects will receive 730 Days of oral difluoromethylornithine (DFMO) at a dose of 750 mg/m2 ± 250 mg/m2 BID (strata 1, 2, 3, and 4) OR 2500 mg/m2 BID (stratum 1B) on each day of study.
Drug: Difluoromethylornithine (DFMO)
Subjects will receive 730 Days of oral difluoromethylornithine (DFMO) at a dose of 750 mg/m2 ± 250 mg/m2 BID (strata 1, 2, 3, and 4) OR 2500 mg/m2 BID (stratum 1B) on each day of study.
Other Names:
  • eflornithine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Number of participants with event free survival (EFS) during study.
Time Frame: 2 years
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Length of time that participants experience Overall Survival (OS)
Time Frame: 7 years
7 years
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Time Frame: 2 years
2 years
Peak Plasma Concentration (Cmax)
Time Frame: 1 year
Pharmacokinetic assay
1 year
Area under the plasma concentration versus time curve (AUC)
Time Frame: 1 year
Pharmacokinetic assay
1 year
Time to reach Peak Plasma Concentration (Tmax)
Time Frame: 1 year
Pharmacokinetic assay
1 year
Number of participants with ODC (Ornithine decarboxylase) single nucleotide polymorphisms.
Time Frame: 1 year
1 year

Collaborators and Investigators

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

Sponsor

Giselle Sholler

Collaborators

Beat NB Cancer Foundation
Team Parker for Life

Investigators

  • Study Chair: Giselle Sholler, MD, Beat Childhood Cancer at Atrium Health

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)

February 1, 2016

Primary Completion (Estimated)

February 1, 2028

Study Completion (Estimated)

February 1, 2033

Study Registration Dates

First Submitted

February 4, 2016

First Submitted That Met QC Criteria

February 5, 2016

First Posted (Estimated)

February 10, 2016

Study Record Updates

Last Update Posted (Actual)

April 8, 2024

Last Update Submitted That Met QC Criteria

April 4, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NMTRC014

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

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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