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

Study Overview
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Brief Summary
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RATIONALE: Beta-glucan may stimulate the immune system and stop tumor cells from growing. Monoclonal antibodies, such as 3F8, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving beta-glucan together with monoclonal antibody 3F8 may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of beta-glucan when given together with monoclonal antibody 3F8 in treating patients with metastatic neuroblastoma.

Detailed Description
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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.

Official Title
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Phase I Study of Oral Yeast β-Glucan and Intravenous Anti-GD2 Monoclonal Antibody 3F8 Among Patients With Metastatic Neuroblastoma

Conditions
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Neuroblastoma

Intervention / Treatment
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* Biological: beta-glucan
* Biological: monoclonal antibody 3F8
* Other: immunohistochemistry staining method
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 0 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Beta-Glucan and Monoclonal Antibody 3F8<br>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 periodica | Biological: beta-glucan<br> <br> Biological: monoclonal antibody 3F8<br> <br> Other: immunohistochemistry staining method<br> <br> Other: laboratory biomarker analysis<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent neuroblastoma, regional neuroblastoma, stage 4S neuroblastoma, disseminated neuroblastoma