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

NCT ID: NCT00492167

Last Updated: 2022-03-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-09-09
• Study Completion Date: 2022-03-04

Brief Summary

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

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.

Conditions

Neuroblastoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Beta-Glucan and Monoclonal Antibody 3F8

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

Group Type: EXPERIMENTAL

beta-glucan

Intervention Type: BIOLOGICAL

monoclonal antibody 3F8

Intervention Type: BIOLOGICAL

immunohistochemistry staining method

Intervention Type: OTHER

laboratory biomarker analysis

Intervention Type: OTHER

Interventions

beta-glucan

Intervention Type: BIOLOGICAL

monoclonal antibody 3F8

Intervention Type: BIOLOGICAL

immunohistochemistry staining method

Intervention Type: OTHER

laboratory biomarker analysis

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

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)

• Minimum Eligible Age: 0 Years
• Maximum Eligible Age: 120 Years
• 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

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Shakeel Modak, MD

Role: STUDY_CHAIR

Memorial Sloan Kettering Cancer Center

Brian H. Kushner, MD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Countries

United States

References

Cardenas FI, Mauguen A, Cheung IY, Kramer K, Kushner BH, Ragupathi G, Cheung NV, Modak S. Phase I Trial of Oral Yeast-Derived beta-Glucan to Enhance Anti-GD2 Immunotherapy of Resistant High-Risk Neuroblastoma. Cancers (Basel). 2021 Dec 14;13(24):6265. doi: 10.3390/cancers13246265.

Reference Type: DERIVED

PMID: 34944886 (View on PubMed)

Related Links

http://www.mskcc.org/mskcc/html/44.cfm

Memorial Sloan Kettering Cancer Center

Other Identifiers

MSKCC-05073

Identifier Type: -

Identifier Source: secondary_id

05-073

Identifier Type: -

Identifier Source: org_study_id