Phase I Study of Oral Yeast β-Glucan and Intravenous Anti-GD2 Monoclonal Antibody 3F8 Among Patients With Metastatic Neuroblastoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 45
- 试验地点
- 1
- 主要终点
- Toxicity
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 0 Years 至 120 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •Hyperbilirubinemia from TPN
- •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)
排除标准
- 未提供
研究组 & 干预措施
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
干预措施: beta-glucan (Biological)
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
干预措施: monoclonal antibody 3F8 (Biological)
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
干预措施: immunohistochemistry staining method (Other)
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
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Toxicity
时间窗: 2 years
次要结局
未报告次要终点