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

Primary Purpose

Neuroblastoma

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

beta-glucan

monoclonal antibody 3F8

immunohistochemistry staining method

laboratory biomarker analysis

About this trial

This is an interventional treatment trial for Neuroblastoma focused on measuring recurrent neuroblastoma, regional neuroblastoma, stage 4S neuroblastoma, disseminated neuroblastoma

Eligibility Criteria

0 Years - 120 Years (Child, Adult, Older Adult)All SexesDoes not accept 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)

Sites / Locations

Memorial Sloan Kettering Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Beta-Glucan and Monoclonal Antibody 3F8

Arm Description

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

Outcomes

Primary Outcome Measures

Toxicity

Secondary Outcome Measures

Full Information

NCT ID

NCT00492167

First Posted

June 25, 2007

Last Updated

March 4, 2022

Sponsor

Memorial Sloan Kettering Cancer Center

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT00492167

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2022

Overall Recruitment Status

Completed

Study Start Date

September 9, 2005 (Actual)

Primary Completion Date

March 4, 2022 (Actual)

Study Completion Date

March 4, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Memorial Sloan Kettering Cancer Center

Collaborators

National Cancer Institute (NCI)

4. Oversight

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Neuroblastoma

Keywords

recurrent neuroblastoma, regional neuroblastoma, stage 4S neuroblastoma, disseminated neuroblastoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

45 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Beta-Glucan and Monoclonal Antibody 3F8

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

beta-glucan

Intervention Type

Biological

Intervention Name(s)

monoclonal antibody 3F8

Intervention Type

Other

Intervention Name(s)

immunohistochemistry staining method

Intervention Type

Other

Intervention Name(s)

laboratory biomarker analysis

Primary Outcome Measure Information:

Title

Toxicity

Time Frame

2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

0 Years

Maximum Age & Unit of Time

120 Years

Accepts Healthy Volunteers

Eligibility 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)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Shakeel Modak, MD

Organizational Affiliation

Memorial Sloan Kettering Cancer Center

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Brian H. Kushner, MD

Organizational Affiliation

Memorial Sloan Kettering Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Memorial Sloan Kettering Cancer Center

City

New York

State/Province

New York

ZIP/Postal Code

10065

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

34944886

Citation

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.

Results Reference

derived

Links:

URL

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

Description

Memorial Sloan Kettering Cancer Center

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

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