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

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00492167

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arm

197.8

Actual Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Neuroblastoma	Biological: beta-glucan Biological: monoclonal antibody 3F8 Other: immunohistochemistry staining method Other: laboratory biomarker analysis	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

45 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Sep 9, 2005

Actual Primary Completion Date :

Mar 4, 2022

Actual Study Completion Date :

Mar 4, 2022

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: 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

Biological: beta-glucan

Biological: monoclonal antibody 3F8

Other: immunohistochemistry staining method

Other: laboratory biomarker analysis

Outcome Measures

Primary Outcome Measures

Toxicity [2 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

0 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065

Sponsors and Collaborators

Memorial Sloan Kettering Cancer Center
National Cancer Institute (NCI)

Investigators

Study Chair: Shakeel Modak, MD, Memorial Sloan Kettering Cancer Center
Principal Investigator: Brian H. Kushner, MD, Memorial Sloan Kettering Cancer Center