Single-agent Rituximab as Maintenance Treatment Versus Observation After Combined Induction Immunochemotherapy With Fludarabine, Cyclophosphamide and Rituximab in Patients Older Than 65 Years With Previously Untreated Chronic Lymphocytic Leukemia: a Phase III Trial of FILO
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 542
- 试验地点
- 2
- 主要终点
- Progression-free survival
研究概览
简要总结
RATIONALE: Classical chemotherapy does not cure advanced chronic lymphocytic leukemia (CLL) despite new drugs. Rituximab is a monoclonal antibody directed against CD20 surface antigen on B lymphocytes and leads to apoptosis of CD20 positive B lymphocytes. The highest response rate yet published in the treatment of first-line CLL has been obtained by the association of fludarabine, cyclophosphamide and rituximab (FCR). Now, the question is whether this response can be improved, as some trials showed that eradication of minimal residual disease (MRD) in CLL is associated with a longer treatment-free and overall survival. Maintenance therapy using rituximab has been recently approved as a means of prolonging remission in patients with indolent non Hodgkin's lymphoma. Maintenance therapy with rituximab could be of interest in treatment of MRD in CLL and prolonging remission and survival times.
PURPOSE: The overall purpose of the study is to determine the value of immunotherapy maintenance with single agent rituximab in comparison with no further treatment (observation ) for previously untreated chronic lymphocytic leukaemia in elderly (>65 years) patients who respond to induction immunochemotherapy with FCR.
详细描述
OBJECTIVES:
Primary
- To demonstrate superiority, in terms of 3-year progression-free survival (PFS), of rituximab maintenance over observation in patients who are in complete or partial response (CR or PR) after induction therapy comprising fludarabine, cyclophosphamide, and rituximab.
Secondary
- To determine event-free survival, disease-free survival, overall survival, and time to next treatment, all from time of randomization.
- To determine overall response rate (CR and PR) according to NCI and iwCLL criteria
- To assess the rate of phenotypic response (minimal residual disease).
- To assess duration of phenotypic and NCI and iwCLL clinical responses.
- To determine response rates and time-related parameters in biological subgroups.
- To determine rates of treatment-related adverse events.
- To evaluate CD4/CD8 counts, immunoglobulin levels, and incidence of Coombs-positive hemolytic anemia.
- To study pharmacokinetics of rituximab during induction and maintenance.
- To evaluate the prognostic impact of the immunoglobulin FcγRIIIA genotype.
- To assess quality of life.
- To study pharmacoeconomics.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 65 Years 至 —（Older 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
Observation
Observation every 8 weeks during 2 years
rituximab arm
rituximab :500 mg/m² every 8 weeks during 2 years
干预措施: Rituximab (Biological)
结局指标
主要结局
Progression-free survival
时间窗: randomization until disease progression or death
Progression-free survival is defined as the time from randomization to the first occurrence of disease progression, relapse or death from any cause; using iwCLL criteria
次要结局
- Event-free survival(randomization until disease progression, death, new CLL treatment, and secondary cancer)
- Disease-free survival(first documented CR until relapse)
- Overall survival(randomization until death)
- Time to next treatment(randomization until new CLL treatment)
- Overall response rate(baseline up to approximately 66 months)
- Phenotypic response rate(randomization up to approximately 60 months)
- Rates of treatment-related adverse events(safety since baseline)
- Pharmacokinetics of rituximab(baseline up to approximately 36 months)
- Quality of life(baseline up to approximately 30 months)