Overview

This trial is active, not recruiting.

Condition neuroblastoma
Treatments anti-gd2 murine igg3 monoclonal antibody 3f8
Phase phase 2
Sponsor Memorial Sloan Kettering Cancer Center
Collaborator National Cancer Institute (NCI)
Start date July 2003
End date December 2016
Trial size 340 participants
Trial identifier NCT00072358, 03-077, MSKCC-03077

Summary

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
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.
anti-gd2 murine igg3 monoclonal antibody 3f8 patients (enrolled on study for treatment of primary refractory disease), the
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.
(Experimental)
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.
anti-gd2 murine igg3 monoclonal antibody 3f8 For Group 2 patients (enrolled on study in CR/VGPR, i.e., with no evidence of disease),
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.

Primary Outcomes

Measure
Efficacy at completion of treatment
time frame: 3 years
Relapse-free survival every 3 months
time frame: 3 years

Secondary Outcomes

Measure
Compare granulocyte activation in patients treated with short-term vs prolonged daily exposure to sargramostim (GM-CSF) after 4 courses
time frame: 3 years
Simplify treatment with consequent reduction in cost
time frame: 3 years

Eligibility Criteria

Male or female participants of any age.

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

Additional Information

Official title Phase II Study of Anti-GD2 3F8 Antibody and GM-CSF for High-Risk Neuroblastoma
Principal investigator Brian H. Kushner, MD
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.
Trial information was received from ClinicalTrials.gov and was last updated in October 2015.
Information provided to ClinicalTrials.gov by Memorial Sloan Kettering Cancer Center.