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.

Condition	Treatment or Intervention	Phase
disseminated neuroblastoma localized unresectable neuroblastoma recurrent neuroblastoma regional neuroblastoma stage 4S neuroblastoma	Drug: monoclonal antibody 3F8  Drug: sargramostim  Procedure: antibody therapy  Procedure: biological response modifier therapy  Procedure: colony-stimulating factor therapy  Procedure: cytokine therapy  Procedure: monoclonal antibody therapy	Phase II

Further Study Details: 

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 (or IV over 2 hours during course 4 only) on days -5 to 11 and monoclonal antibody 3F8 IV over 1.5 hours on days 0-4 and 7-11. Treatment repeats every 3 weeks for 4 courses and then every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Patients with evaluable disease (primary refractory bone marrow disease) are removed from study after course 3 if there is no evidence of response.

Beginning after 2 courses (or after 1 course if human anti-mouse antibody develops and precludes timely administration of course 2) of GM-CSF and monoclonal antibody 3F8, patients also receive oral isotretinoin twice daily on days 1-14. Isotretinoin repeats approximately every 28 days for 6 courses.

PROJECTED ACCRUAL: A total of 15-90 patients (15-45 patients with evaluable disease [primary refractory bone marrow disease] and 45 patients with no evaluable disease [no evidence of disease]) will be accrued for this study within 3 years.

Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of high-risk neuroblastoma by histology OR bone marrow metastases and high urine catecholamine levels, including any of the following International Neuroblastoma Staging System stages:
• Stage 4 with (any age) OR without (over 1 year of age) MYCN amplification
• MYCN-amplified stage 3 (unresectable, any age)
• MYCN-amplified stage 4S
• Evaluable disease that is resistant to standard therapy (incomplete response in bone marrow) with no MIBG-avid soft tissue tumor and no progressive disease OR no evaluable or measurable disease (i.e., patient is in complete/very good partial remission)

PATIENT CHARACTERISTICS: Age

• Any age

Performance status

• Not specified

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• No concurrent grade 3 or greater hepatic toxicity

Renal

• No concurrent grade 3 or greater renal toxicity

Cardiac

• No concurrent grade 3 or greater cardiac toxicity

Pulmonary

• No concurrent grade 3 or greater pulmonary toxicity

Other

• Not pregnant
• Negative pregnancy test
• No human anti-mouse antibody (HAMA) titer greater than 1,000 Elisa units/mL
• No concurrent grade 3 or greater neurologic toxicity
• No concurrent grade 3 or greater gastrointestinal toxicity
• No history of allergy to mouse proteins
• No active life-threatening infection

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

New York
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States; Recruiting

Study chairs or principal investigators

Brian H. Kushner, MD,  Principal Investigator,  Memorial Sloan-Kettering Cancer Center   

Study ID Numbers:  CDR0000339611; MSKCC-03077; NCT00072358
Record last reviewed:  October 2003
Last Updated:  December 6, 2004
Record first received:  November 4, 2003
ClinicalTrials.gov Identifier:  NCT00072358
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08