Monoclonal Antibody 3F8 and Sargramostim in Treating Patients With Neuroblastoma

NCT ID: NCT00072358

Last Updated: 2022-05-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 291 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-07-31
• Study Completion Date: 2021-01-15

Brief 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.

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.

Conditions

Neuroblastoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

anti-GD2 murine IgG3 monoclonal antibody 3F8

Intervention Type: BIOLOGICAL

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.

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.

Group Type: EXPERIMENTAL

anti-GD2 murine IgG3 monoclonal antibody 3F8

Intervention Type: BIOLOGICAL

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: BIOLOGICAL

Other Intervention Names

patients (enrolled on study for treatment of primary refractory disease), the; break between end of a cycle of 3F8/GM-CSF and start of next cycle is 2-to-4-weeks through 4; cycles after achievement of CR in BM; subsequent breaks are ~8 weeks. In this; group, isotretinoin is started after documentation of response to, and after; >2 cycles of, 3F8/GM-CSF.; 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.

Eligibility Criteria

Inclusion 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

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Brian H. Kushner, MD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Countries

United States

References

Kushner BH, Modak S, Basu EM, Roberts SS, Kramer K, Cheung NK. Posterior reversible encephalopathy syndrome in neuroblastoma patients receiving anti-GD2 3F8 monoclonal antibody. Cancer. 2013 Aug 1;119(15):2789-95. doi: 10.1002/cncr.28137. Epub 2013 Apr 30.

Reference Type: DERIVED

PMID: 23633099 (View on PubMed)

Cheung IY, Hsu K, Cheung NK. Activation of peripheral-blood granulocytes is strongly correlated with patient outcome after immunotherapy with anti-GD2 monoclonal antibody and granulocyte-macrophage colony-stimulating factor. J Clin Oncol. 2012 Feb 1;30(4):426-32. doi: 10.1200/JCO.2011.37.6236. Epub 2011 Dec 27.

Reference Type: DERIVED

PMID: 22203761 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

MSKCC-03077

Identifier Type: -

Identifier Source: secondary_id

03-077

Identifier Type: -

Identifier Source: org_study_id