Biological Therapy in Treating Patients With Neuroblastoma That Has Not Responded to Previous Treatment

OBJECTIVES:

• Determine the efficacy of beta-glucan, isotretinoin, and sargramostim (GM-CSF) in enhancing monoclonal antibody 3F8-mediated ablation in patients with high-risk refractory neuroblastoma.
• Determine the antitumor activity of this regimen, in terms of assessing disease status in the bone marrow by real-time quantitative reverse transcription polymerase chain reaction, in these patients.
• Determine the toxicity of this regimen in these patients.

OUTLINE: This is an open-label study. Patients are stratified according to refractory disease (primary refractory [never had disease progression or disease recurrence] vs secondary refractory [recurrent disease that did not respond completely to reinduction therapy]).

• Courses 1 and 2: Patients receive sargramostim (GM-CSF) subcutaneously once daily on days -5 to 11. Patients also receive oral beta-glucan once daily on days -2 to 11 and monoclonal antibody (MOAB) 3F8 IV over 30-90 minutes on days 0-4 and 7-11.
• Courses 3 and 4: Patients receive GM-CSF, beta-glucan, and MOAB 3F8 as above. Patients also receive oral isotretinoin twice daily on days -2 to 11.

Treatment repeats every 2-4 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years.

PROJECTED ACCRUAL: A total of 27-74 patients (10-33 for stratum 1 and 17-41 for stratum 2) will be accrued for this study.

DISEASE CHARACTERISTICS:

• Diagnosis of neuroblastoma, as defined by 1 of the following:

• Histologically confirmed disease
• Bone marrow metastases plus high urine catecholamines
• High-risk disease meeting 1 of the following stage criteria:

• Stage IV, with 1 of the following:

• Any age with MYCN amplification
• > 18 months of age without MYCN amplification
• Stage III, with both of the following:

• Any age with MYCN amplification
• Unresectable disease
• Stage 4S with MYCN amplification
• Measurable or evaluable soft tissue disease
• Relapsed disease resistant to standard induction chemotherapy and salvage therapy

PATIENT CHARACTERISTICS:

Age

• Any age

Performance status

• Not specified

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• No severe hepatic toxicity ≥ grade 3

Renal

• No severe renal toxicity ≥ grade 3

Cardiovascular

• No severe cardiac toxicity ≥ grade 3

Pulmonary

• No severe pulmonary toxicity ≥ grade 3

Other

• Not pregnant
• Negative pregnancy test
• No severe neurologic toxicity ≥ grade 3
• No severe gastrointestinal toxicity ≥ grade 3
• No other severe major organ dysfunction except ototoxicity
• No history of allergy to mouse proteins
• No active life-threatening infection
• No human anti-mouse antibody titer > 1,000 ELISA units/mL

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified