Monoclonal Antibody 3F8 and Sargramostim in Treating Patients With Neuroblastoma

Memorial Sloan Kettering Cancer Center (MSK)

Status and phase: Completed; Phase 2

Conditions: Neuroblastoma

Treatments: Biological: anti-GD2 murine IgG3 monoclonal antibody 3F8

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00072358

MSKCC-03077

03-077

Details and patient eligibility

About

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.

Full 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.

Enrollment: 291 patients

Sex: All

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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291 participants in 2 patient groups

patients have refractory bone marrow disease

Experimental group

Description:

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.

Treatment:

Biological: anti-GD2 murine IgG3 monoclonal antibody 3F8

Biological: anti-GD2 murine IgG3 monoclonal antibody 3F8

patients have no evidence of disease

Experimental group

Description:

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.

Treatment:

Biological: anti-GD2 murine IgG3 monoclonal antibody 3F8

Biological: anti-GD2 murine IgG3 monoclonal antibody 3F8