Official Title: “Phase II Study of Anti-GD2 3F8 Antibody and Biologic Response Modifiers for High-Risk Neuroblastoma”

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.

Study Type: Interventional

Study Design: Treatment, Open Label

Study Primary Completion Date: November 2006

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.

Intervention(s) in this Clinical Trial

• Biological: beta-glucan
• Biological: monoclonal antibody 3F8
• Biological: sargramostim
• Drug: isotretinoin

Primary Measures

• Disease response as assessed by PT-PC at the end of 4 courses
  • Safety Issue?: No

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Memorial Sloan-Kettering Cancer Center

Overall Clinical Trial Officials and Contacts

Nai-Kong V. Cheung, MD, PhD Study Chair Memorial Sloan-Kettering Cancer Center  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00089258

Study ID Number: CDR0000378186

ClinicalTrials.gov Identifier: NCT00089258

Health Authority: United States: Federal Government

Clinical trial summary from the National Cancer Institute's PDQ® database