Multicentre, Non-Randomised, Open-Label Phase II Study to Evaluate the Efficacy and Safety of Induction Treatment With Rituximab, Fludarabine, Cyclophosphamide, Followed by Rituximab Maintenance Therapy (R-Fc-Rm) in the First Line Treatment of Chronic Lymphocytic Leukaemia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 86
- 试验地点
- 33
- 主要终点
- Percentage of Participants With CR Achieved After the Rituximab, Fludarabine, and Cyclophosphamide Regimen
研究概览
简要总结
This single arm study will assess the efficacy and safety of rituximab in combination with fludarabine and cyclophosphamide, followed by rituximab maintenance therapy, as first line treatment of participants with CLL.
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
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •CLL according to World Health Organization diagnostic criteria
- •Active disease
- •No previous treatment
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
排除标准
- •Transformation to aggressive B-cell malignancy (prolymphocytic leukemia, large-cell lymphoma, Hodgkin's lymphoma)
- •Other malignancies except for localized skin cancer
- •Continuous systemic corticosteroid treatment
- •Known infection with hepatitis B or C
研究组 & 干预措施
Rituximab + Fludarabine + Cyclophosphamide
Participants will receive 6 cycles (cycle length = 28 days) of treatment with rituximab (375 milligrams per square meter [mg/m^2] as intravenous [IV] infusion on Day 0 of Cycle 1 and 500 mg/m^2 as IV infusion on Day 1 of Cycles 2-6); fludarabine (25 mg/m^2 on Days 1-3) and cyclophosphamide (250 mg/m^2 on Days 1-3). Participants with a partial or complete response and appropriate neutrophil conditions will receive maintenance treatment with rituximab (375 mg/m^2 as IV infusion every 2 months) from 3 months after Day 1 Cycle 6 up to a total of 18 doses or up to 3 years after Cycle 6.
干预措施: Cyclophosphamide (Drug)
Rituximab + Fludarabine + Cyclophosphamide
Participants will receive 6 cycles (cycle length = 28 days) of treatment with rituximab (375 milligrams per square meter [mg/m^2] as intravenous [IV] infusion on Day 0 of Cycle 1 and 500 mg/m^2 as IV infusion on Day 1 of Cycles 2-6); fludarabine (25 mg/m^2 on Days 1-3) and cyclophosphamide (250 mg/m^2 on Days 1-3). Participants with a partial or complete response and appropriate neutrophil conditions will receive maintenance treatment with rituximab (375 mg/m^2 as IV infusion every 2 months) from 3 months after Day 1 Cycle 6 up to a total of 18 doses or up to 3 years after Cycle 6.
干预措施: Fludarabine (Drug)
Rituximab + Fludarabine + Cyclophosphamide
Participants will receive 6 cycles (cycle length = 28 days) of treatment with rituximab (375 milligrams per square meter [mg/m^2] as intravenous [IV] infusion on Day 0 of Cycle 1 and 500 mg/m^2 as IV infusion on Day 1 of Cycles 2-6); fludarabine (25 mg/m^2 on Days 1-3) and cyclophosphamide (250 mg/m^2 on Days 1-3). Participants with a partial or complete response and appropriate neutrophil conditions will receive maintenance treatment with rituximab (375 mg/m^2 as IV infusion every 2 months) from 3 months after Day 1 Cycle 6 up to a total of 18 doses or up to 3 years after Cycle 6.
干预措施: Rituximab (Drug)
结局指标
主要结局
Percentage of Participants With CR Achieved After the Rituximab, Fludarabine, and Cyclophosphamide Regimen
时间窗: Month 9
CR was defined as no adenopathies (ADPs) and visceromegalies (VSMs) in physical examination (PE); no general symptoms (Sx); lymphocytes (Lymph) in peripheral blood less than (\<) 4000 per cubic millimeter (mm\^3); normalization of peripheral blood parameters: neutrophils (Neut) greater than (\>) 1500/mm\^3, platelets (Plt) \>100,000/mm\^3, hemoglobin (Hb) \>11 grams per deciliter (g/dL) without transfusion; normocellular bone marrow (BM) with \<30% Lymph; BM aspirate/biopsy with no evidence of infiltration of lymphoid nodules.
次要结局
- Percentage of Participants With Clinical Response of CR or PR as Assessed by Multiparameter Flow Cytometry(Post-Induction Phase (IP): at 6 months; during Maintenance Phase (MP): at Cycles 9, 12, 15, 18 (cycle length = 2 months); during Follow-Up (FU): at Follow-Up Months 6, 12, 18, 24, 30, 36)
- Percentage of Participants With Clinical Response of CR or PR Among Participants With Negative Minimal Residual Disease (MRD) as Assessed by Multiparameter Flow Cytometry(Post-Induction Phase: at 6 months; during Maintenance Phase: at Cycles 9, 12, 15, 18 (cycle length = 2 months); during Follow-Up: at Follow-Up Months 6, 12, 18, 24, 36)
- Percentage of Participants With CR With Incomplete Bone Marrow Recovery (CRi)(Baseline up to progressive disease (PD) or death due to any cause, whichever occurred first (up to 92 months))
- Percentage of Participants Who Died(Baseline up to death due to any cause (up to 92 months))
- Overall Survival (OS)(Baseline up to death due to any cause (up to 92 months))
- Percentage of Participants With PD or Death(Baseline up to PD or death due to any cause, whichever occurred first (up to 92 months))
- Progression-Free Survival (PFS)(Baseline up to PD or death due to any cause, whichever occurred first (up to 92 months))
- Treatment-Free Survival (TFS)(Baseline up to PD or death due to any cause, whichever occurred first (up to 92 months))
- Duration of Response (DOR)(From first CR or PR up to detectable MRD or disease occurrence/PD, whichever occurred first (up to 92 months))
- Percentage of Participants With Cluster of Differentiation (CD) 38 Cells >/=30% in Peripheral Blood(Post-Induction Phase: at 6 months; during Maintenance Phase: at Cycles 9, 12, 15, 18 (cycle length = 2 months); during Follow-Up: at Follow-Up Months 6, 12, 18, 24, 30, 36)
- Percentage of Participants With Genetic Abnormalities(Post-Induction Phase: at 6 months; during Maintenance Phase: at Cycles 9, 12, 15, 18 (cycle length = 2 months))
- Percentage of Participants With Positive and Negative Zeta-Chain-Associated Protein Kinase 70 (ZAP-70) Expression(Post-Induction Phase: at 6 months; during Maintenance Phase: at Cycles 9, 12, 15, 18 (cycle length = 2 months); during Follow-Up: at Follow-Up Months 6, 12, 18, 24, 30, 36)
- Percentage of Participants With Immunoglobulin Heavy Locus (IgH) Rearrangement(Post-Induction Phase: at 6 months; during Maintenance Phase: at Cycles 9, 12, 15, 18 (cycle length = 2 months); during Follow-Up: at Follow-Up Months 6, 12, 18, 24, 30, 36)