A Phase 3, Multicenter, Randomized, Openlabel, Parallel-Group Study of the Efficacy and Safety of Lenalidomide (Revlimid®) Versus Chlorambucil as First-Line Therapy for Previously Untreated Elderly Patients With B-Cell Chronic Lymphocytic Leukemia (The Origin Trial)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Celgene
- 入组人数
- 450
- 试验地点
- 165
- 主要终点
- Kaplan-Meier Estimate of Progression Free Survival (PFS)
研究概览
简要总结
The purpose of this study is to determine the safety and efficacy of lenalidomide as a first line therapy in treating patients with B-cell Chronic Lymphocytic Leukemia. This study will compare the effects (good and bad) of lenalidomide with chlorambucil.
详细描述
After notification from the US Food and Drug Administration (FDA) on 12 July 2013, Celgene agreed to discontinue the lenalidomide treatment for all patients due to an imbalance in the number of deaths in patients treated with lenalidomide versus patients treated with chlorambucil. No specific causality for this imbalance has been identified to date. Investigators were instructed to immediately discontinue all participants from experimental lenalidomide treatment and inform their patients accordingly. Participants on the Chlorambucil arm may continue up to 12 months (13 cycles) with the last participant completing in March 2014. All randomized participants will continue to be followed for overall survival and secondary primary malignancies.
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
- •Must sign an informed consent form.
- •Age ≥ 65 years
- •Must be able to adhere to the study visit schedule and other protocol requirements.
- •Must have a documented diagnosis of B-cell CLL.
- •Must have an Eastern Cooperative Oncology Group (ECOG) performance status score of ≤
- •Must agree to follow pregnancy precautions as required by the protocol.
- •Must agree to receive counseling related to teratogenic and other risks of lenalidomide.
- •Must agree not to donate blood or semen as defined by the protocol
排除标准
- •Prior treatment for B-cell CLL.
- •Any medical condition, that would prevent the subject from signing the informed consent form.
- •Active infections requiring systemic antibiotics.
- •Systemic infection that has not resolved > 2 months prior to initiating lenalidomide
- •Pregnant or lactating females.
- •Participation in any clinical study or having taken any investigational therapy within 28 days.
- •Known presence of alcohol and/or drug abuse.
- •Central nervous system (CNS) involvement.
- •Prior history of malignancies, other than CLL, unless the subject has been free of the disease for ≥3 years. Exceptions include the following:
- •Basal cell carcinoma of the skin
- •Squamous cell carcinoma of the skin
- •Carcinoma in situ of the cervix
- •Carcinoma in situ of the breast
- •Incidental histologic finding of prostate cancer (TNM stage of T1a or T1b)
- •History of renal failure requiring dialysis.
- •Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) and/or Hepatitis C Virus (HCV) infection.
- •Prior therapy with lenalidomide.
- •Evidence of TLS at screening
- •Presence of specific hematology and/or chemistry abnormalities
- •Uncontrolled hyperthyroidism or hypothyroidism
- •Venous thromboembolism within one year
- •≥ Grade-2 neuropathy
- •Uncontrolled autoimmune hemolytic anemia or thrombocytopenia
- •Disease transformation [i.e. Richter's Syndrome (lymphomas) or prolymphocytic leukemia]
研究组 & 干预措施
1 - Lenalidomide
1 - Lenalidomide
干预措施: Lenalidomide (Drug)
2- Chlorambucil
2- Chlorambucil
干预措施: Chlorambucil (Drug)
结局指标
主要结局
Kaplan-Meier Estimate of Progression Free Survival (PFS)
时间窗: From first dose of study drug to date of data cut-off of 18 Feb 2013; up to approximately 39 months
Progression-free survival was defined as the time from randomization to the first documented progression confirmed per investigator's assessment or death due to any cause on study, whichever occurred first. The progression date was assigned to the earliest time when any progression was observed without prior missing assessments. If withdrawal of consent or lost to follow-up occurred before documented progression or death, then these observations were censored at the date when the last complete tumor assessments determined a lack of progression
Kaplan-Meier Estimate of Progression Free Survival (PFS) With a Later Cut-off Date of 14 March 2014
时间窗: From randomization to data cut off date of 31 March 2014; median follow up time for all participants was 12.6 months
Progression-free survival was defined as the time from randomization to the first documented progression confirmed per investigator's assessment or death due to any cause on study, whichever occurred first. Progressive disease included lymphadenopathy, an appearance of any new lesion such as enlarged lymph nodes (\> 1.5 cm), splenomegaly, hepatomegaly or other organ infiltrates, an increase by 50% or more in greatest determined diameter of any previous site or an increase by 50% or more in the sum of the product of diameters of multiple nodes. The progression date was assigned to the earliest time when any progression was observed without prior missing assessments. If withdrawal of consent or lost to follow-up occurred before documented progression or death, then these observations were censored at the date when the last complete tumor assessments determined a lack of progression.
次要结局
- Number of Participants With Adverse Events With a Later Cut-off Date of 31 March 2014(From randomization to the data cut-off date of 31 March 2014; Up to 53 months; maximum duration of exposure for Lenalidomide was 1140 days and 406 days for Chlorambucil)
- Percentage of Participants With the Best Overall Response Based on the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Guidelines(Up to data cut-off date of 18 Feb 2013; approximately 39 months)
- Percentage of Participants With a Best Overall Response Based on IWCLL Guidelines With a Later Cut-off Date of 31 March 2014(Up to data cut-off of 31 March 2014; approximately 53 months)
- Time to Response for a Later Cut-off Date of 31 March 2014(Up to data cut-off of 31 March 2014; up to approximately 53 months)
- Kaplan Meier Estimate for Overall Survival at the Final Analysis(Up to the last patient last visit date of 19 May 2018; median follow-up for all participants was 46.7 months)
- Number of Participants With Adverse Events (AEs)(From randomization up to data cut-off of 18 Feb 2013; Up to approximately 39 months; maximum duration of exposure for Lenalidomide was 1086 days and 406 days for Chlorambucil)
- Time to Response(Up to data cut-off of 18 Feb 2013; up to approximately 39 months)
- Kaplan Meier Estimate of Overall Survival(Up to data cut off of 31 March 2014; median follow-up for all participants was 18.8 months)
- Kaplan-Meier Estimate for Duration of Response With a Later Cut-off Date of 31 March 2014(Up to data cut-off of 31 March 2014; up to approximately 53 months)
- Kaplan-Meier Estimate for Duration of Response(Up to data cut-off of 18 Feb 2013; up to approximately 39 months)
- Number of Participants and Types of Subsequent Anti-cancer Therapies Received Post Treatment(Up to the last patient last visit date of 19 May 2018; median follow-up for all participants was 46.7 months)
- Functional Assessment of Cancer Therapy-General to Create the FACT-Leukemia (FACT-Leu) Quality of Life Instrument(Day 1 and once every 8 weeks)
- Euro Quality of Life Five Dimension (EQ-5D) Questionnaire(Day 1 and once every 8 weeks)