A Randomized Study to Assess the Effect on Response Rate of MabThera (Rituximab) Added to a Standard Chemotherapy, Bendamustine or Chlorambucil, in Patients With Chronic Lymphocytic Leukemia
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 357
- 主要终点
- Percentage of Participants Achieving Confirmed Complete Response (CR) According to International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 Guidelines in the First-Line Subpopulation After 6 Cycles of Therapy
研究概览
简要总结
This randomized, open-label, parallel group study will assess the effect on response rate and the safety of MabThera added to either bendamustine or chlorambucil in patients with chronic lymphocytic leukemia. Patients will be randomized to receive six 4-week cycles of either A) MabThera (375mg/m2 iv day 1 of cycle 1, 500mg/m2 iv cycles 2-6) plus bendamustine (90mg/m2 as first-line or 70mg/m2 as second-line therapy, iv on days 1 and 2, cycles 1-6), or B)MabThera plus chlorambucil (10mg/m2 po daily, days 1-7, cycles 1-6). Patients in group B can receive up to 6 further cycles of chlorambucil as monotherapy. Anticipated time on study treatment is 6-12 months, and target sample size is 600-700 individuals.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •adult patients, >/=18 years of age
- •chronic lymphocytic leukemia
- •active CLL with progressive Binet stage B or C
- •ineligible for treatment with fludarabine
- •for second line patients, only pretreatment with rituximab and/or chlorambucil is allowed
- •EOCG performance status >/=2
排除标准
- •patients who have relapsed within <12 months of first dose of prior rituximab or chlorambucil first-line therapy
- •previous or planned stem cell transplantation
- •radioimmunotherapy within 6 months prior to starting study treatment
- •transformation to aggressive B-cell malignancy
- •any other concurrent anti-cancer therapy, or glucocorticoid >/=20mg daily prednisolone or equivalent
研究组 & 干预措施
B
干预措施: chlorambucil (Drug)
B
干预措施: rituximab [MabThera/Rituxan] (Drug)
A
干预措施: bendamustine (Drug)
A
干预措施: rituximab [MabThera/Rituxan] (Drug)
结局指标
主要结局
Percentage of Participants Achieving Confirmed Complete Response (CR) According to International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 Guidelines in the First-Line Subpopulation After 6 Cycles of Therapy
时间窗: At least 2 months after completion of therapy (up to 32 weeks)
The definition of confirmed CR required all of the following criteria as assessed at least 2 months after completion of therapy: peripheral blood lymphocytes less than (\<) 4 times 10\^9 cells per liter (cells/L); absence of significant lymphadenopathy, hepatomegaly, or splenomegaly due to chronic lymphocytic leukemia (CLL) involvement; absence of constitutional symptoms; normal complete blood count (CBC) without need for transfusion or exogenous growth factors, as exhibited by neutrophils at least (\>/=) 1.5 times 10\^9 cells/L, platelets greater than (\>) 100 times 10\^9 cells/L, and hemoglobin \> 11.0 grams per deciliter (g/dL); normocellular bone marrow (BM) aspirate with \< 30 percent (%) lymphocytes; absence of lymphoid nodules; and BM biopsy without CLL activity. The percentage of participants achieving confirmed CR was calculated as the number of participants meeting the above criteria divided by the number of participants analyzed, multiplied by 100.
次要结局
- Percentage of Participants Achieving Confirmed CR According to IWCLL 2008 Guidelines in the Second-Line Subpopulation After 6 Cycles of Therapy(At least 2 months after completion of therapy (up to 32 weeks))
- Percentage of Participants Achieving Confirmed CR According to IWCLL 2008 Guidelines in the Pooled Population After 6 Cycles of Therapy(At least 2 months after completion of therapy (up to 32 weeks))
- Percentage of Participants Experiencing PD or Death in the First-Line Subpopulation(End of Cycles 3 and 6 (both treatment arms), end of Cycles 7 to 12 (Rituximab + Chlorambucil arm), after an additional 8 weeks as confirmation of response, then every 3 months for 1 year, then every 6 months until study cutoff (up to 4.5 years))
- Progression-Free Survival (PFS) in the First-Line Subpopulation(End of Cycles 3 and 6 (both treatment arms), end of Cycles 7 to 12 (Rituximab + Chlorambucil arm), after an additional 8 weeks as confirmation of response, then every 3 months for 1 year, then every 6 months until study cutoff (up to 4.5 years))
- Percentage of Participants With Tumor Response of CR or CRi Experiencing PD or Death in the First-Line Subpopulation(End of Cycles 3 and 6 (both treatment arms), end of Cycles 7 to 12 (Rituximab + Chlorambucil arm), after an additional 8 weeks as confirmation of response, then every 3 months for 1 year, then every 6 months until study cutoff (up to 4.5 years))
- Disease-Free Survival (DFS) in the First-Line Subpopulation(End of Cycles 3 and 6 (both treatment arms), end of Cycles 7 to 12 (Rituximab + Chlorambucil arm), after an additional 8 weeks as confirmation of response, then every 3 months for 1 year, then every 6 months until study cutoff (up to 4.5 years))
- Percentage of Participants Experiencing PD, Documented Intake of New Leukemia Therapy, or Death in the First-Line Subpopulation(End of Cycles 3 and 6 (both treatment arms), end of Cycles 7 to 12 (Rituximab + Chlorambucil arm), after an additional 8 weeks as confirmation of response, then every 3 months for 1 year, then every 6 months until study cutoff (up to 4.5 years))
- Event-Free Survival (EFS) in the First-Line Subpopulation(End of Cycles 3 and 6 (both treatment arms), end of Cycles 7 to 12 (Rituximab + Chlorambucil arm), after an additional 8 weeks as confirmation of response, then every 3 months for 1 year, then every 6 months until study cutoff (up to 4.5 years))
- Percentage of Participants With Documented Intake of New Leukemia Therapy in the First-Line Subpopulation(During Cycles 1 to 6 (both treatment arms), Cycles 7 to 12 (Rituximab + Chlorambucil arm), after an additional 8 weeks, then every 3 months for 1 year, then every 6 months until study cutoff (up to 4.5 years))
- Time to Next Leukemia Treatment (TNLT) in the First-Line Subpopulation(During Cycles 1 to 6 (both treatment arms), Cycles 7 to 12 (Rituximab + Chlorambucil arm), after an additional 8 weeks, then every 3 months for 1 year, then every 6 months until study cutoff (up to 4.5 years))
- Percentage of Participants Achieving a Best Overall Response of CR, CR With Incomplete Marrow Recovery (CRi), Partial Response (PR), or Nodular PR (nPR) in the First-Line Subpopulation(After 3 and 6 treatment cycles and from Baseline to the end-of-treatment (EOT) visit, completed within 10 days before cutoff for data collection)
- Percentage of Participants by Disease Response Category in the First-Line Subpopulation(After 6 treatment cycles and at the confirmation of response assessment at least 12 weeks later (up to 36 weeks))
- Percentage of Participants With Tumor Response of CR, CRi, PR, or nPR Experiencing PD or Death in the First-Line Subpopulation(End of Cycles 3 and 6 (both treatment arms), end of Cycles 7 to 12 (Rituximab + Chlorambucil arm), after an additional 8 weeks as confirmation of response, then every 3 months for 1 year, then every 6 months until study cutoff (up to 4.5 years))
- Duration of Response in the First-Line Subpopulation(End of Cycles 3 and 6 (both treatment arms), end of Cycles 7 to 12 (Rituximab + Chlorambucil arm), after an additional 8 weeks as confirmation of response, then every 3 months for 1 year, then every 6 months until study cutoff (up to 4.5 years))
- Percentage of Participants Experiencing Death in the First-Line Subpopulation(End of Cycles 3 and 6 (both treatment arms), end of Cycles 7 to 12 (Rituximab + Chlorambucil arm), after an additional 8 weeks as confirmation of response, then every 3 months for 1 year, then every 6 months until study cutoff (up to 4.5 years))
- Overall Survival (OS) in the First-Line Subpopulation(End of Cycles 3 and 6 (both treatment arms), end of Cycles 7 to 12 (Rituximab + Chlorambucil arm), after an additional 8 weeks as confirmation of response, then every 3 months for 1 year, then every 6 months until study cutoff (up to 4.5 years))
- Percentage of Participants Achieving Molecular Response in the First-Line Subpopulation(Up to 4 months after the last treatment cycle (up to 40 weeks))
- Number of Participants With Positive and Negative Outcome for MRD in the First-Line Subpopulation(After 6 treatment cycles (up to 24 weeks))
- Proportion of Malignant B-cells in Normal B-cells Among Participants With a Positive Outcome for MRD in the First-Line Subpopulation(After 6 treatment cycles (up to 24 weeks))