Double Blind Randomized Phase III Study of Lenalidomide Maintenance Versus Placebo in Responding Elderly Patients With DLBCL and Treated With R-CHOP in First Line
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 650
- 试验地点
- 157
- 主要终点
- Progression-Free-Survival (PFS)
研究概览
简要总结
This study is designed as a phase III, randomized, double-blind, placebo-controlled trial to explore the effect of maintenance therapy with lenalidomide versus placebo on progression-free survival (PFS) in patients treated with R-CHOP responding to induction therapy
For the primary efficacy variable, PFS, an improvement in median PFS from 38.6 months for Treatment Arm B to 54 months for Treatment Arm A (corresponding to a 2-year PFS of 65% vs 73.6%), is considered clinically relevant.
详细描述
Patients should have received at least 6 and up to 8 cycles of the R-CHOP 14 or R-CHOP 21 regimen or 6 R-CHOP-14 or -21 completed by 2 Rituximab alone in accordance to local preferences.
Patients can be registered to participate in the study at two time points:
- At time of initial diagnosis and study enrolment (signature of informed consent) before the first cycle of treatment with R-CHOP.
- At randomization (signature of informed consent) after treatment in first line with R-CHOP and have reached at least PR or CR.
Evaluation of the response to R-CHOP must be in accordance with Revised Response Criteria for Malignant Lymphoma(2007).
Stratification: Before randomization, the patients will be stratified according to the country and the response to R-CHOP (PR vs CR).
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 60 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •For patients registered at the time of initial diagnosis
- •Patient with histologically proven CD20+ diffuse large B cel LYMPHOMA (DLBCL) 5WHO classification 2008) including clinical subtypes (primitive mediastinal, intravascular, etc.). Patients with De Novo Transformed DLBCL from low grade lymphoma (Follicular, other..) may also be included. Patients with DLBCL associated with some small cell infiltration in bone marrow may also be included Or CD20+ B-cell lymphoma with intermediate features between DLBCL and Burkitt or with intermediate features between DLBCL and classical Hodgkin lymphoma Or CD20+ Follicular lymphoma grade 3B Or CD20+ Aggressive B-cell lymphoma unclassifiable
- •previous untreated with chemo- or radiotherapy
- •For patients registered after response evaluation to first line treatment with R-CHOP:
- •Patient with histologically proven CD20+ diffuse large B cell LYMPHOMA (DLBCL) 5WHO classification 2008) including clinical subtypes (primitive mediastinal, intravascular, etc.). Patients with De Novo Transformed DLBCL from low grade lymphoma (Follicular, other..) may also be included. Patients with DLBCL associated with some small cell infiltration in bone marrow may also be included Or CD20+ B-cell lymphoma with intermediate features between DLBCL and Burkitt or with intermediate features between DLBCL and classical Hodgkin lymphoma Or CD20+ Follicular lymphoma grade 3B Or CD20+ Aggressive B-cell lymphoma unclassifiable
- •Have reached a CR or PR after first line treatment with at least 6 cycles of R-CHOP 14 regimens and up to 8 cycles of R-CHOP21
- •Previously untreated with Radiotherapy
- •For all patients:
- •aged from 60 to 80 years at time of registration
- •Ann Arbor stages II-IV at time of initial diagnosis
- •aaIPI> 1 at time of initial diagnosis
- •ECOG performance status 0-2
- •Minimum life expectancy of 3 months
- •Following laboratory values at screening:
- •ANC≥ 1000.10^6/L and Platelets≥60000.10^6/L
- •AST<5*ULN, ALT<5*ULN, Total Bilirubin<1,5*ULN
- •Creatinine clearance>30mL/min
- •Women are are using effective contraception, are not pregnant and agree not to become pregnant during participation in the trial and after end of study. Men agree not to father a child during participation in the trial and during the 12 months thereafter.
- •Having previously signed a written informed consent form
排除标准
- •Any other histological type of Lymphoma, Burkitt included.
- •Any history of treated or non treated small B-cell lymphoma
- •Central nervous system or meningeal involvement by lymphoma
- •Contraindication to any drug contained in the chemotherapy regimen Myocardial infarction during last 3 months or unstable coronary disease or uncontrolled chronic symptomatic congestive heart insufficiency NYHA III-IV
- •Uncontrolled hypertension
- •Uncontrolled diabetes mellitus as defined by the investigator
- •Active systemic infection requiring treatment
- •previously known HIV positive serology
- •Active hepatitis B or C
- •Prior history of malignancies other than lymphoma within 3 years
- •Serious medical or psychiatric illness
研究组 & 干预措施
Lenalidomide
Lenalidomide daily for 3 weeks every 4 weeks for 24 months
干预措施: Lenalidomide (Drug)
Placebo
Placebo daily for 3 weeks every 4 weeks for 24 months
干预措施: Placebo (Drug)
结局指标
主要结局
Progression-Free-Survival (PFS)
时间窗: Final PFS analysis will be realized when the number of events (160) has been reached or at the latest when the last patient into the study will finish follow up. The approximate schedule will be 75 months after the first patient randomized.
PFS will be measured from the date of randomization to the date of first documented disease progression or death. Progression data will be assigned to the earliest time when any progression is observed without prior missing assessments during the study up to the end of the follow up phase.
次要结局
- Percentage of patients who convert from PR (partial response) to CR (complete response)(24 months)
- Overall survival (OS)(5 years)
- Event-Free Survival (EFS)(5 years)
- Response rate at the end of maintenance treatment(24 months)
- Safety of lenalidomide in maintenance(5 years)
- PFS2(5 years)