Monoclonal Antibody 3F8 and Sargramostim in Treating Patients With Neuroblastoma

Neuroblastoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00072358
• Other study ID #: 03-077
• Secondary ID: MSKCC-03077
• Status: Completed
• Phase: Phase 2
• Start date: July 2003
• Est. completion date: January 15, 2021

Study information

• Verified date: April 2022
• Source: Memorial Sloan Kettering Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 291
• Est. completion date: January 15, 2021
• Est. primary completion date: January 15, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Neuroblastoma

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	Memorial Sloan-Kettering Cancer Center	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy at Completion of Treatment		3 years
Primary	Relapse-free Survival Every 3 Months		3 years
Secondary	Compare Granulocyte Activation in Patients Treated With Short-term vs Prolonged Daily Exposure to Sargramostim (GM-CSF) After 4 Courses		3 years
Secondary	Simplify Treatment With Consequent Reduction in Cost		3 years