Eflornithine (DFMO) and Etoposide for Relapsed/Refractory Neuroblastoma

April 4, 2024 updated by: Giselle Sholler

Phase II Trial of Eflornithine (DFMO) and Etoposide for Relapsed/Refractory Neuroblastoma

Difluoromethylornithine (DFMO) will be used in an open label, multicenter, study in combination with etoposide for subjects with relapsed/refractory neuroblastoma.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Difluoromethylornithine (DFMO) will be used in an open label, multicenter, study in combination with etoposide for subjects with relapsed/refractory neuroblastoma.

In this study subjects will receive six 21-day cycles of Etoposide and DFMO followed by an additional 630 days of DFMO alone.

Subjects will be evaluated in 3 arms:

• Arm 1: Subjects who show no active disease after receiving any additional therapy for neuroblastoma that was refractory to standard induction/consolidation therapy.

Refractory: Subjects with progressive disease on upfront therapy OR did not have at least PR on induction OR required additional second line therapy to achieve remission who are now in first remission.

  • Arm 2: Subjects who have previously relapsed and currently show no active disease (in CR2 or greater).
  • Arm 3: Subjects who are relapsed or refractory with active disease.

Study Type

Interventional

Enrollment (Estimated)

131

Phase

  • Phase 2

Expanded Access

Available outside the clinical trial. See expanded access record.

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 Contact Backup

Study Locations

  • Canada
    • Manitoba
      • Winnipeg, Manitoba, Canada
        • Recruiting
        • CancerCare Manitoba
        • Contact:
        • Principal Investigator:
          • Issai Vanan, MD
    • Quebec
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35201
        • Recruiting
        • University of Alabama, Children's Alabama
        • Contact:
        • Principal Investigator:
          • Rebecca McFall, MD
    • Arkansas
      • Little Rock, Arkansas, United States, 72202
        • Recruiting
        • Arkansas Children's Hospital
        • Principal Investigator:
          • Kevin Bielamowicz, MD
        • Contact:
    • California
      • Oakland, California, United States, 94609
        • 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:
    • Connecticut
      • Hartford, Connecticut, United States, 06106
        • Recruiting
        • Connecticut Children's Hospital
        • Principal Investigator:
          • Michael Isakoff, MD
        • Contact:
    • Florida
      • Orlando, Florida, United States, 32806
        • Recruiting
        • Arnold Palmer Hospital for Children
        • Principal Investigator:
          • Amy Smith, 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, 30912
        • 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
    • Kentucky
      • Louisville, Kentucky, United States, 40201
    • 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
        • Cardinal Glennon Children's Hospital
        • Principal Investigator:
          • William Ferguson, MD
        • Contact:
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Recruiting
        • Hackensack University Medical Center
        • Contact:
        • Principal Investigator:
          • Derek Hanson, MD
    • North Carolina
      • Charlotte, North Carolina, United States, 28204
        • Recruiting
        • Levine Children's Hospital
        • Contact:
        • Principal Investigator:
          • Thomas Russell, MD
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Recruiting
        • Cleveland Clinic Children's
        • Contact:
        • Principal Investigator:
          • Stacey Zahler, 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, 02901
        • Recruiting
        • Hasbro Children's Hospital
        • Contact:
        • Principal Investigator:
          • Bradley DeNardo, MD
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Not yet recruiting
        • Medical University of South Carolina
        • Principal Investigator:
          • Jaqueline Kraveka, MD
        • Contact:
    • Texas
      • Austin, Texas, United States, 78723
      • Dallas, Texas, United States, 75235
        • Recruiting
        • Children's Medical Center Dallas
        • Principal Investigator:
          • Tanya Watt, MD
        • Contact:
    • Virginia
      • Norfolk, Virginia, United States, 23507
        • Recruiting
        • Children's Hospital of The King's Daughters
        • Contact:
        • Principal Investigator:
          • Eric Lowe, MD
    • 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

No older than 31 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 with history of relapsed/refractory neuroblastoma.
  • All patients must have completed upfront therapy with at least 4 cycles of aggressive multi-drug chemotherapy.
  • Specific Criteria by Arm:

Arms 1 and 2:

Subjects with no active disease:

i. No evidence of residual disease by CT/MRI and MIBG scan (or PET for patients who have a history of MIBG non-avid disease).

o Note: Patients with residual masses detected by CT/MRI may be considered in CR if their MIBG is negative or if MIBG positive and evaluated by PET and found to have negative PET scans; biopsy confirmation may be considered if there is still reasonable concern for persistent disease but is not required.

ii. No evidence of disease metastatic to bone marrow.

Arm 3:

Measurable or evaluable disease, including at least one of the following:

Measurable tumor by CT or MRI; or a positive MIBG and PET; or positive bone marrow biopsy/aspirate in at least one site.

  • Timing from prior therapy: Enrollment (first dose of DFMO) no later than 60 days from last dose of the most recent therapy.

  • Subjects must have fully recovered from the acute toxic effects of all prior anti- cancer chemotherapy and be within the following timelines:

    1. Myelosuppressive chemotherapy: Must not have received within 2 weeks of enrollment onto this study (6 weeks if prior nitrosourea).
    2. Hematopoietic growth factors: At least 5 days since the completion of therapy with a growth factor.
    3. Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with a biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the Study Chair.
    4. Immunotherapy: At least 6 weeks since the completion of any type of immunotherapy, e.g. tumor vaccines, CAR-T cells.
    5. Anti-GD2 Monoclonal antibodies: At least 2 weeks must have elapsed since prior treatment with a monoclonal antibody.
    6. XRT: At least 14 days since the last treatment except for radiation delivered with palliative intent to a non-target site.

    7. Stem Cell Transplant:

      1. Allogeneic: No evidence of active graft vs. host disease
      2. Allo/Auto: ≥ 2 months must have elapsed since transplant.
    8. MIBG Therapy: At least 8 weeks since treatment with MIBG therapy
  • Subjects must have a Lansky or Karnofsky Performance Scale score of 60% or higher.
  • Life expectancy > 2 months
  • 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.

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

    • Hematological: Total absolute neutrophil count ANC ≥750/μL
    • Liver: Subjects must have adequate liver function as defined by AST and ALT <5x upper limit of normal (Normal=45), Bilirubin <1.5x upper limit normal (Normal=1.0). Normal PT, PTT, fibrinogen.
    • Renal: Adequate renal function defined as (perform one of the following): Creatinine clearance or radioisotope GFR 70 mL/min/1.73 m2 or greater or a serum creatinine based on age/gender
  • 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 guidelines must be obtained from all subjects (or patients' legal representative).

Exclusion Criteria:

  • BSA of <0.25 m2.
  • Subjects that received DFMO at a dose higher than 1000mg/m2 BID prior to this study are not eligible.
  • Subjects that received a dose of DFMO in combination with etoposide are not eligible.
  • 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: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Eflornithine (DFMO)

In this study subjects will receive six 21-day cycles of Etoposide and DFMO followed by an additional 630 days of DFMO alone.

Etoposide will be given at 50 mg/m2/dose PO daily for the first 14 days of each 21 days until 6 cycles of etoposide are completed.

DFMO (difluoromethylornithine) will be given at a dose of 1000 mg/m2 BID on each day of study.
Drug: Eflornithine
DFMO (difluoromethylornithine) will be given at a dose of 1000 mg/m2 BID on each day of study.
Other Names:
  • DFMO
  • difluoromethylornithine

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

To evaluate the efficacy of difluoromethylornithine (DFMO) in combination with etoposide in patients with relapsed/refractory neuroblastoma, based upon:

o Event free survival (EFS) from time of enrollment.
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

To evaluate the efficacy of difluoromethylornithine (DFMO) in combination with etoposide in patients with relapsed/refractory neuroblastoma, based upon:

o Overall Survival (OS) from time of enrollment.
7 years
Determine the Overall Response Rate (ORR) of Participants using INSS Response Evaluation Criteria.
Time Frame: 2 years

To evaluate the efficacy of difluoromethylornithine (DFMO) in combination with etoposide in patients with relapsed/refractory neuroblastoma, based upon:

o Response Rate for patients with active disease (Arm 3) using International Neuroblastoma Staging System (INSS) Response Evaluation Criteria.
2 years
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Time Frame: 2 years plus 30 days
To monitor the safety and tolerability profile of difluoromethylornithine (DFMO) in combination with etoposide in pediatric and young adult patients with relapsed/refractory neuroblastoma.
2 years plus 30 days

Collaborators and Investigators

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

Sponsor

Giselle Sholler

Collaborators

Beat NB Cancer Foundation
K C Pharmaceuticals Inc.
Team Parker for Life

Investigators

  • Study Chair: Giselle Sholler, 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)

September 25, 2020

Primary Completion (Estimated)

October 1, 2028

Study Completion (Estimated)

October 1, 2033

Study Registration Dates

First Submitted

March 6, 2020

First Submitted That Met QC Criteria

March 6, 2020

First Posted (Actual)

March 10, 2020

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

  • BCC015

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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