A Phase I/II Trial of Escalating Dose of Yttrium-90-labeled Anti-CD20 Monoclonal Antibody in Combination With High-Dose Etoposide and Cyclophosphamide Followed by AHSCT for Patients With Relapsed B-Cell Non-Hodgkin's Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 54
- 主要终点
- 5-Year Overall Survival (Phase II)
研究概览
简要总结
RATIONALE: Radiolabeled monoclonal antibodies, such as yttrium Y 90 ibritumomab tiuxetan, can find cancer cells and carry tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy, such as etoposide and cyclophosphamide, work in different ways to kill cancer cells or stop them from growing. Giving radiolabeled monoclonal antibodies together with etoposide and cyclophosphamide before a peripheral blood stem cell transplant may be an effective treatment for non-Hodgkin lymphoma.
PURPOSE: This phase I/II trial is studying the side effects and best dose of yttrium Y 90 ibritumomab tiuxetan when given together with etoposide and cyclophosphamide followed by an autologous stem cell transplant and to see how well it works in treating patients with non-Hodgkin lymphoma.
详细描述
OBJECTIVES:
- To evaluate the safety and efficacy of a new preparative regimen of yttrium Y 90 ibritumomab tiuxetan in combination with high-dose etoposide and cyclophosphamide followed by autologous stem cell transplantation (ASCT) for treatment of patients with poor-risk, relapsed, or refractory non-Hodgkin lymphoma (NHL).
- To determine the maximum tolerated dose of yttrium Y 90 ibritumomab tiuxetan which can be given with high-dose etoposide and high-dose cyclophosphamide followed by ASCT in patients with NHL.
- To perform dosimetry study to estimate the radiation dose delivered to the tumor and normal organs.
- To evaluate the short-term and long-term complications of this new preparative regimen.
OUTLINE: This is a phase I does-escalation study of yttrium Y 90 ibritumomab tiuxetan followed by an open-label phase II study.
- Preparation for transplantation: Peripheral blood stem cells (PBSCs) are collected via leukapheresis. Samples are analyzed by cytogenetic studies, immunophenotyping, and gene rearrangement. Patients with an adequate number of collected CD34-positive cells (≥ 3 times 10^6 /kg) proceed to radioimmunotherapy.
- Radioimmunotherapy: Patients receive yttrium Y 90 ibritumomab tiuxetan IV on days -21 and -14. Patients undergo bone marrow biopsy and dose estimation on day -7.
- Chemotherapy: Patients receive etoposide IV on day -4 and cyclophosphamide IV over 2 hours on day -2.
- Transplantation: Patients undergo reinfusion of PBSCs on day 1.
- Growth factor therapy: Patients receive filgrastim (G-CSF) IV beginning on day 1 and continuing until blood counts recover.
Treatment continues in the absence of disease progression or unacceptable toxicity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Zevalin 1000 cGy + VP-16 40 mg/kg + Cytoxan 100 mg/kg
- Preparation for AHSCT: Peripheral blood stem cells (PBSCs) are collected via leukapheresis. Samples are analyzed by cytogenetic studies, immunophenotyping, and gene rearrangement. Patients with an adequate number of collected CD34-positive cells (≥ 3 times 10^6 /kg) proceed to radioimmunotherapy.
- Radioimmunotherapy: Patients receive yttrium Y 90 ibritumomab tiuxetan and undergo bone marrow biopsy and dose estimation.
- Chemotherapy: Patients receive etoposide IV and cyclophosphamide IV
- AHSCT: Patients undergo reinfusion of PBSCs.
- Growth factor therapy: Patients receive filgrastim (G-CSF) IV. Treatment continues in the absence of disease progression or unacceptable toxicity.
干预措施: filgrastim (Biological)
Zevalin 1000 cGy + VP-16 40 mg/kg + Cytoxan 100 mg/kg
- Preparation for AHSCT: Peripheral blood stem cells (PBSCs) are collected via leukapheresis. Samples are analyzed by cytogenetic studies, immunophenotyping, and gene rearrangement. Patients with an adequate number of collected CD34-positive cells (≥ 3 times 10^6 /kg) proceed to radioimmunotherapy.
- Radioimmunotherapy: Patients receive yttrium Y 90 ibritumomab tiuxetan and undergo bone marrow biopsy and dose estimation.
- Chemotherapy: Patients receive etoposide IV and cyclophosphamide IV
- AHSCT: Patients undergo reinfusion of PBSCs.
- Growth factor therapy: Patients receive filgrastim (G-CSF) IV. Treatment continues in the absence of disease progression or unacceptable toxicity.
干预措施: cyclophosphamide (Drug)
Zevalin 1000 cGy + VP-16 40 mg/kg + Cytoxan 100 mg/kg
- Preparation for AHSCT: Peripheral blood stem cells (PBSCs) are collected via leukapheresis. Samples are analyzed by cytogenetic studies, immunophenotyping, and gene rearrangement. Patients with an adequate number of collected CD34-positive cells (≥ 3 times 10^6 /kg) proceed to radioimmunotherapy.
- Radioimmunotherapy: Patients receive yttrium Y 90 ibritumomab tiuxetan and undergo bone marrow biopsy and dose estimation.
- Chemotherapy: Patients receive etoposide IV and cyclophosphamide IV
- AHSCT: Patients undergo reinfusion of PBSCs.
- Growth factor therapy: Patients receive filgrastim (G-CSF) IV. Treatment continues in the absence of disease progression or unacceptable toxicity.
干预措施: etoposide (Drug)
Zevalin 1000 cGy + VP-16 40 mg/kg + Cytoxan 100 mg/kg
- Preparation for AHSCT: Peripheral blood stem cells (PBSCs) are collected via leukapheresis. Samples are analyzed by cytogenetic studies, immunophenotyping, and gene rearrangement. Patients with an adequate number of collected CD34-positive cells (≥ 3 times 10^6 /kg) proceed to radioimmunotherapy.
- Radioimmunotherapy: Patients receive yttrium Y 90 ibritumomab tiuxetan and undergo bone marrow biopsy and dose estimation.
- Chemotherapy: Patients receive etoposide IV and cyclophosphamide IV
- AHSCT: Patients undergo reinfusion of PBSCs.
- Growth factor therapy: Patients receive filgrastim (G-CSF) IV. Treatment continues in the absence of disease progression or unacceptable toxicity.
干预措施: AHSCT (Procedure)
Zevalin 1000 cGy + VP-16 40 mg/kg + Cytoxan 100 mg/kg
- Preparation for AHSCT: Peripheral blood stem cells (PBSCs) are collected via leukapheresis. Samples are analyzed by cytogenetic studies, immunophenotyping, and gene rearrangement. Patients with an adequate number of collected CD34-positive cells (≥ 3 times 10^6 /kg) proceed to radioimmunotherapy.
- Radioimmunotherapy: Patients receive yttrium Y 90 ibritumomab tiuxetan and undergo bone marrow biopsy and dose estimation.
- Chemotherapy: Patients receive etoposide IV and cyclophosphamide IV
- AHSCT: Patients undergo reinfusion of PBSCs.
- Growth factor therapy: Patients receive filgrastim (G-CSF) IV. Treatment continues in the absence of disease progression or unacceptable toxicity.
干预措施: yttrium Y 90 ibritumomab tiuxetan (Radiation)
Zevalin 1000 cGy + VP-16 60 mg/kg + Cytoxan 100 mg/kg
- Preparation for AHSCT: Peripheral blood stem cells (PBSCs) are collected via leukapheresis. Samples are analyzed by cytogenetic studies, immunophenotyping, and gene rearrangement. Patients with an adequate number of collected CD34-positive cells (≥ 3 times 10^6 /kg) proceed to radioimmunotherapy.
- Radioimmunotherapy: Patients receive yttrium Y 90 ibritumomab tiuxetan and undergo bone marrow biopsy and dose estimation.
- Chemotherapy: Patients receive etoposide IV and cyclophosphamide IV
- AHSCT: Patients undergo reinfusion of PBSCs.
- Growth factor therapy: Patients receive filgrastim (G-CSF) IV. Treatment continues in the absence of disease progression or unacceptable toxicity.
干预措施: filgrastim (Biological)
Zevalin 1000 cGy + VP-16 60 mg/kg + Cytoxan 100 mg/kg
- Preparation for AHSCT: Peripheral blood stem cells (PBSCs) are collected via leukapheresis. Samples are analyzed by cytogenetic studies, immunophenotyping, and gene rearrangement. Patients with an adequate number of collected CD34-positive cells (≥ 3 times 10^6 /kg) proceed to radioimmunotherapy.
- Radioimmunotherapy: Patients receive yttrium Y 90 ibritumomab tiuxetan and undergo bone marrow biopsy and dose estimation.
- Chemotherapy: Patients receive etoposide IV and cyclophosphamide IV
- AHSCT: Patients undergo reinfusion of PBSCs.
- Growth factor therapy: Patients receive filgrastim (G-CSF) IV. Treatment continues in the absence of disease progression or unacceptable toxicity.
干预措施: cyclophosphamide (Drug)
Zevalin 1000 cGy + VP-16 60 mg/kg + Cytoxan 100 mg/kg
- Preparation for AHSCT: Peripheral blood stem cells (PBSCs) are collected via leukapheresis. Samples are analyzed by cytogenetic studies, immunophenotyping, and gene rearrangement. Patients with an adequate number of collected CD34-positive cells (≥ 3 times 10^6 /kg) proceed to radioimmunotherapy.
- Radioimmunotherapy: Patients receive yttrium Y 90 ibritumomab tiuxetan and undergo bone marrow biopsy and dose estimation.
- Chemotherapy: Patients receive etoposide IV and cyclophosphamide IV
- AHSCT: Patients undergo reinfusion of PBSCs.
- Growth factor therapy: Patients receive filgrastim (G-CSF) IV. Treatment continues in the absence of disease progression or unacceptable toxicity.
干预措施: etoposide (Drug)
Zevalin 1000 cGy + VP-16 60 mg/kg + Cytoxan 100 mg/kg
- Preparation for AHSCT: Peripheral blood stem cells (PBSCs) are collected via leukapheresis. Samples are analyzed by cytogenetic studies, immunophenotyping, and gene rearrangement. Patients with an adequate number of collected CD34-positive cells (≥ 3 times 10^6 /kg) proceed to radioimmunotherapy.
- Radioimmunotherapy: Patients receive yttrium Y 90 ibritumomab tiuxetan and undergo bone marrow biopsy and dose estimation.
- Chemotherapy: Patients receive etoposide IV and cyclophosphamide IV
- AHSCT: Patients undergo reinfusion of PBSCs.
- Growth factor therapy: Patients receive filgrastim (G-CSF) IV. Treatment continues in the absence of disease progression or unacceptable toxicity.
干预措施: AHSCT (Procedure)
Zevalin 1000 cGy + VP-16 60 mg/kg + Cytoxan 100 mg/kg
- Preparation for AHSCT: Peripheral blood stem cells (PBSCs) are collected via leukapheresis. Samples are analyzed by cytogenetic studies, immunophenotyping, and gene rearrangement. Patients with an adequate number of collected CD34-positive cells (≥ 3 times 10^6 /kg) proceed to radioimmunotherapy.
- Radioimmunotherapy: Patients receive yttrium Y 90 ibritumomab tiuxetan and undergo bone marrow biopsy and dose estimation.
- Chemotherapy: Patients receive etoposide IV and cyclophosphamide IV
- AHSCT: Patients undergo reinfusion of PBSCs.
- Growth factor therapy: Patients receive filgrastim (G-CSF) IV. Treatment continues in the absence of disease progression or unacceptable toxicity.
干预措施: yttrium Y 90 ibritumomab tiuxetan (Radiation)
结局指标
主要结局
5-Year Overall Survival (Phase II)
时间窗: From peripheral stem cell infusion (Day0 ASCT) to death due to any cause, assessed up to 5 years
Overall survival (OS) was measured from peripheral stem cell infusion to death from any cause. It was estimated using the Kaplan-Meier method; the 95% confidence interval was calculated using Greenwood's formula. \[Breslow NE, Day NE. Statistical methods in cancer research: volume II, the design and analysis of cohort studies. IARC Sci Publ 1987;82:1-406.\]
5-Year Disease-free Survival (Phase II)
时间窗: From peripheral stem cell infusion (Day0 ASCT) to first observation of relapse or death due to any cause, whichever comes first, assessed up to 5 years
Disease-free survival (DFS) was defined as time from peripheral stem cell infusion to relapse or death. In a clinical trial, measuring the disease-free survival is one way to see how well a new treatment works. Disease-free survival was estimated using the Kaplan-Meier method; the 95% confidence interval was calculated using Greenwood's formula \[Breslow NE, Day NE. Statistical methods in cancer research: volume II, the design and analysis of cohort studies. IARC Sci Publ 1987;82:1-406.\]
Number of Patients Achieving Complete Response (CR)
时间窗: Assessed up to 5 years post-ASCT
Complete response is defined as complete disappearance of all measureable evidence of non-evaluable disease. No new lesions. No disease related symptoms. No evidence of non-evaluable disease, including normalization of markers and other abnormal lab values. All measureable, evaluable and non-evaluable lesions and sites must be assessed using the same techniques as baseline.
Number of Patients With Grade 3 or Greater Toxicity
时间窗: From initial of study treatment to Day 100 post-ASCT
The NCI Common Toxicity Criteria (CTC Version 2.0) are used. The patients, whose toxicities are grade 3 or greater and at possibly related to the study treatment, are reported.
次要结局
未报告次要终点