Monoclonal Antibody 3F8 and Sargramostim in Treating Patients With Neuroblastoma

April 21, 2022 updated by: Memorial Sloan Kettering Cancer Center

Phase II Study of Anti-GD2 3F8 Antibody and GM-CSF for High-Risk Neuroblastoma

RATIONALE: Monoclonal antibodies, such as monoclonal antibody 3F8, can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Colony-stimulating factors, such as sargramostim, may increase the number of immune cells found in bone marrow or peripheral blood. Combining monoclonal antibody 3F8 with sargramostim may cause a stronger immune response and kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combining monoclonal antibody 3F8 with sargramostim in treating patients who have neuroblastoma.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

  • Determine the efficacy of sargramostim (GM-CSF) in enhancing monoclonal antibody 3F8-mediated ablation in patients with high-risk neuroblastoma.
  • Determine the prognostic impact of minimal residual bone marrow disease on relapse-free survival of patients treated with this regimen.
  • Compare the effects of short-term (2-hour intravenous) vs prolonged (subcutaneous release) daily GM-CSF on granulocyte activation, in order to establish the optimal route for tumor-cell kill in these patients.

OUTLINE: This is an open-label study. Patients are stratified according to evaluable disease (yes [primary refractory bone marrow disease] vs no [no evidence of disease]).

Patients receive sargramostim (GM-CSF) subcutaneously on days -5 to 4 and monoclonal antibody 3F8 IV over 0.5-1.5 hours on days 0-4. Treatment repeats every 3 weeks for 4 courses and then every 8 weeks for up to a total of 24 months in the absence of disease progression or unacceptable toxicity.

Beginning after 2 courses of GM-CSF and monoclonal antibody 3F8, patients also receive oral isotretinoin twice daily on days 1-14 (when no monoclonal antibody 3F8 is administered). Treatment with isotretinoin repeats approximately every 28 days for 6 courses.

PROJECTED ACCRUAL: A total of 340 patients will be accrued for this study.

Study Type

Interventional

Enrollment (Actual)

291

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 Locations

  • United States
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan-Kettering Cancer Center

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

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Diagnosis of neuroblastoma by histopathology OR bone marrow metastases and high urine catecholamine levels

  • Disease must meet risk-related treatment guidelines and any of the following International Neuroblastoma Staging System stages:

    • Stage 4 with (any age) OR without (> 18 months of age of age) MYCN amplification
    • MYCN-amplified other than stage 1
  • No evidence of disease (i.e., in complete response/remission or very good partial response/remission) OR disease resistant to standard therapy (i.e., incomplete response in bone marrow)
  • No progressive disease or MIBG-avid soft tissue tumor

PATIENT CHARACTERISTICS:

  • No existing renal, cardiac, hepatic, neurologic, pulmonary, or gastrointestinal toxicity ≥ grade 3
  • No human anti-mouse antibody (HAMA) titer greater than 1,000 Elisa units/mL
  • No history of allergy to mouse proteins
  • No active life-threatening infection
  • Not pregnant
  • Negative pregnancy test

PRIOR CONCURRENT THERAPY:

  • Not specified

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: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: patients have refractory bone marrow disease
This phase II trial of the anti-GD2 murine IgG3 monoclonal antibody 3F8 combined with granulocyte-macrophage colony stimulating factor (GM-CSF) will assess response of minimal residual disease (MRD) in patients with high-risk neuroblastoma (NB) and help establish the optimal way to use GM-CSF.
Biological: anti-GD2 murine IgG3 monoclonal antibody 3F8
The total dosage of 3F8 per cycle is the same as in prior trials (100 mg/m2), administered at 20 mg/m2/day and infused over ~1.5 hr or less (0.5 hr is customary), with analgesics and antihistamines used as needed for expected side-effects. 3F8 is started ~1 hr after completion of GM-CSF administration. GM-CSF is dosed at 250 mcg/m2/day from day -5 to day +1 (Wednesday to Tuesday is customary) , and is 500 mcg/m2/day thereafter (i.e., on days +2 to +4; Wednesday to Friday), as in the predecessor protocol.18,74 Patients come off study if progressive disease occurs or if there is life-threatening grade 4 toxicity from 3F8; otherwise, patients will receive a minimum of 4 cycles of treatment and will continue treatment through 24 months. It is expected that patients will receive ~10 cycles.
Other Names:
  • For Group 2 patients (enrolled on study in CR/VGPR, i.e., with no evidence of disease),
  • the break between end of a cycle and start of next cycle is 2-to-4 weeks through 4 cycles;
  • subsequent breaks are ~8 weeks. Isotretinoin is started after cycle 2 of 3F8/GM-CSF. Road
  • map/schema is in section 4.2. Regarding patients in second or greater CR from relapse in the
  • central nervous system, if they develop early HAMA which precludes timely completion of the
  • minimum of 4 cycles of 3F8/GM-CSF, they are eligible to go off protocol, to be treated with
  • low-dose maintenance regimens of irinotecan,94 temozolomide,95 or the two agents combined;96
  • they can resume treatment with 3F8/GM-CSF if HAMA becomes negative.
Experimental: patients have no evidence of disease
This phase II trial of the anti-GD2 murine IgG3 monoclonal antibody 3F8 combined with granulocyte-macrophage colony stimulating factor (GM-CSF) will assess response of minimal residual disease (MRD) in patients with high-risk neuroblastoma (NB) and help establish the optimal way to use GM-CSF.
Biological: anti-GD2 murine IgG3 monoclonal antibody 3F8
The total dosage of 3F8 per cycle is the same as in prior trials (100 mg/m2), administered at 20 mg/m2/day and infused over ~1.5 hr or less (0.5 hr is customary), with analgesics and antihistamines used as needed for expected side-effects. 3F8 is started ~1 hr after completion of GM-CSF administration. GM-CSF is dosed at 250 mcg/m2/day from day -5 to day +1 (Wednesday to Tuesday is customary) , and is 500 mcg/m2/day thereafter (i.e., on days +2 to +4; Wednesday to Friday), as in the predecessor protocol.18,74 Patients come off study if progressive disease occurs or if there is life-threatening grade 4 toxicity from 3F8; otherwise, patients will receive a minimum of 4 cycles of treatment and will continue treatment through 24 months. It is expected that patients will receive ~10 cycles.
Other Names:
  • For Group 2 patients (enrolled on study in CR/VGPR, i.e., with no evidence of disease),
  • the break between end of a cycle and start of next cycle is 2-to-4 weeks through 4 cycles;
  • subsequent breaks are ~8 weeks. Isotretinoin is started after cycle 2 of 3F8/GM-CSF. Road
  • map/schema is in section 4.2. Regarding patients in second or greater CR from relapse in the
  • central nervous system, if they develop early HAMA which precludes timely completion of the
  • minimum of 4 cycles of 3F8/GM-CSF, they are eligible to go off protocol, to be treated with
  • low-dose maintenance regimens of irinotecan,94 temozolomide,95 or the two agents combined;96
  • they can resume treatment with 3F8/GM-CSF if HAMA becomes negative.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Efficacy at Completion of Treatment
Time Frame: 3 years
3 years
Relapse-free Survival Every 3 Months
Time Frame: 3 years
3 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Compare Granulocyte Activation in Patients Treated With Short-term vs Prolonged Daily Exposure to Sargramostim (GM-CSF) After 4 Courses
Time Frame: 3 years
3 years
Simplify Treatment With Consequent Reduction in Cost
Time Frame: 3 years
3 years

Collaborators and Investigators

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

Sponsor

Memorial Sloan Kettering Cancer Center

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Brian H. Kushner, MD, Memorial Sloan Kettering Cancer Center

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.

General Publications

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

July 1, 2003

Primary Completion (Actual)

January 15, 2021

Study Completion (Actual)

January 15, 2021

Study Registration Dates

First Submitted

November 4, 2003

First Submitted That Met QC Criteria

November 5, 2003

First Posted (Estimate)

November 6, 2003

Study Record Updates

Last Update Posted (Actual)

May 16, 2022

Last Update Submitted That Met QC Criteria

April 21, 2022

Last Verified

April 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 03-077
  • MSKCC-03077

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.

Subscribe