Beta-Glucan and Monoclonal Antibody 3F8 in Treating Patients With Metastatic Neuroblastoma

OBJECTIVES:

Primary

• Determine the clinical toxicity of beta-glucan in combination with monoclonal antibody 3F8 in patients with metastatic neuroblastoma.
• Evaluate the biologic effects of this regimen in these patients.

OUTLINE: This is a dose-escalation study of beta-glucan.

Patients receive oral beta-glucan once daily on days -4 to 12 and monoclonal antibody 3F8 IV over 30-90 minutes on days 1-5 and 8-12. Treatment repeats every 4 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity and with a human antimouse antibody (HAMA) titer < 1,000 U/mL.

Cohorts of 3-6 patients receive escalating doses of beta-glucan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients undergo urine, bone marrow, and blood sample collection periodically for biological studies. Samples are analyzed for antibody-dependent cellular cytotoxicity, complement-mediated cytotoxicity, and serum HAMA response via immunohistochemistry.

After completion of study treatment, patients are followed periodically.

DISEASE CHARACTERISTICS:

• Diagnosis of neuroblastoma by 1 of the following methods:

• Histopathology
• Bone marrow involvement AND elevated urinary catecholamines
• High-risk disease, defined by 1 of the following:

• Stage 4 disease with MYCN amplification (any age) or without MYCN amplification (> 18 months of age)
• MYCN-amplified stage 3 disease (unresectable and any age)
• MYCN-amplified stage 4S disease
• Metastatic disease
• Tumor progression or persistent disease (at metastatic or primary site) after intensive conventional chemotherapy
• Must have evaluable (microscopic marrow metastasis, elevated tumor markers, positive MIBG or PET scans) or measurable (CT scan or MRI) disease documented after completion of prior systemic therapy

PATIENT CHARACTERISTICS:

• Platelet count > 25,000/mm^3
• ANC > 500/mm^3
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No history of allergy to mouse proteins, beta-glucan, mushrooms, or yeast
• No active life-threatening infections
• No severe major organ toxicity

• Concurrent toxicity must be ≤ grade 2 except for the following, which may be grade 3:

• Myelosuppression
• Hearing loss
• Alopecia
• Anorexia
• Nausea
• Hyperbilirubinemia from TPN
• Anxiety
• Hypomagnesemia
• No prior HAMA titer > 1,000 U/mL by ELISA

PRIOR CONCURRENT THERAPY:

• No concurrent supplemental beta-glucan in food (e.g., bran cereals or mushrooms) or as complementary medicine
• No other concurrent systemic anticancer medications (e.g., hormonal agents, chemotherapy, investigational agents, or immunotherapy)

• Concurrent isotretinoin allowed after the second course of study treatment is completed or if the patient develops human antimouse antibody (HAMA)