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

Study Overview
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Brief Summary
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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. Beta-glucan, isotretinoin, and sargramostim may increase the effectiveness of monoclonal antibody 3F8 by making tumor cells more sensitive to the monoclonal antibody. Combining different types of biological therapy may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving beta-glucan, isotretinoin, and sargramostim together with monoclonal antibody 3F8 works in treating patients with neuroblastoma that has not responded to previous treatment.

Detailed Description
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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.

Official Title
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Phase II Study of Anti-GD2 3F8 Antibody and Biologic Response Modifiers for High-risk Neuroblastoma

Conditions
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Neuroblastoma

Intervention / Treatment
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* Biological: beta-glucan
* Biological: monoclonal antibody 3F8
* Biological: sargramostim
* Drug: isotretinoin


Participation Criteria
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Eligibility Criteria
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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
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
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: beta-glucan|nan|
|Biological: monoclonal antibody 3F8|nan|
|Biological: sargramostim|nan|
|Drug: isotretinoin|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease response as assessed by PT-PC at the end of 4 courses |  |  | 

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