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

NCT ID: NCT00089258

Last Updated: 2013-01-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 74 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-07-31

Brief Summary

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

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.

Conditions

Neuroblastoma

Study Design

• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

beta-glucan

Intervention Type: BIOLOGICAL

monoclonal antibody 3F8

Intervention Type: BIOLOGICAL

sargramostim

Intervention Type: BIOLOGICAL

isotretinoin

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role: lead

Principal Investigators

Nai-Kong V. Cheung, MD, PhD

Role: STUDY_CHAIR

Memorial Sloan Kettering Cancer Center

Locations

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Countries

United States

Other Identifiers

MSKCC-04050

Identifier Type: -

Identifier Source: secondary_id

04-050

Identifier Type: -

Identifier Source: org_study_id