A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study To Compare The Efficacy And Safety of Lenalidomide (Revlimid®) Versus Placebo In Subjects With Transufsion-Dependent Anemia Due to IPSS Low Or Imtermidate-1 Risk Myelodysplastic Syndromes Without Deletion 5Q(31) And Unresponsive Or Refractory To Erthropoiesis-Stimulating Agents
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Celgene
- 入组人数
- 239
- 试验地点
- 99
- 主要终点
- Percentage of Participants Who Achieved Red Blood Cell (RBC) Transfusion Independence for ≥ 56 Days as Determined by an Independent Review Committee (IRC)
研究概览
简要总结
The purpose of this study is to investigate whether lenalidomide would reduce the number of red blood cell transfusions (RBC) needed in anemic (RBC transfusion-dependent) participants with low or intermediate-1 risk MDS without a deletion 5q chromosome abnormality. The study also investigated the safety of lenalidomide use in these participants. Two-thirds of the participants received oral lenalidomide and one-third of the participants received oral placebo.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •18 years or older
- •Diagnosis of low or intermediate-1 risk Myelodysplastic (MDS) with any chromosome karyotype except del 5q[31]
- •Anemia that requires red blood cell transfusions
- •Resistant to erythropoiesis stimulating agents (ESAs) or blood erythropoietin level > 500 mU/mL
- •Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤ 2
- •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
- •Must be willing to consent to two or more bone marrow aspirate procedures to be completed during study
排除标准
- •Subjects previously receiving immunomodulating or immunosuppressive agents, or epigenetic or deoxyribonucleic acid (DNA) modulation agents
- •Allergic reaction to thalidomide
- •Renal insufficiency creatinine clearance (CrC1)<40 mL/min by Cockcroft-Gault method)
- •Prior history of cancer, other than MDS, unless the subject has been free of the disease for ≥ 5 years. (Basal cell carcinoma of the skin, carcinoma in situ of the cervix, or stage Tumor (T) 1a or T1b prostate cancer is allowed)
- •Absolute neutrophil count (ANC) < 500/uL
- •Platelets < 50,000/uL
- •Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3X upper limit of normal
- •Uncontrolled hyperthyroidism or hypothyroidism
- •Significant neuropathy
- •Prior stem cell transplantation
- •Anemia due to reasons other than MDS
- •History of deep venous thrombosis (DVT) or pulmonary embolus (PE) within past 3 years
- •Significant active cardiac disease within the past 6 months
- •Known Human Immunodeficiency Virus (HIV) infection; known Hepatitis C infection or active Hepatitis B infection
研究组 & 干预措施
Arm #1 - Lenalidomide plus placebo
Lenalidomide 10 mg by mouth (PO) daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 60 mL/min for at least 168 days until disease progression, intolerable side effects or withdrawal of consent. Lenalidomide 5 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 40 and < 60 mL/min.
干预措施: Lenalidomide (Drug)
Arm #2 - placebo
Three placebo capsules once daily for at least 168 days until disease progression occurred, intolerable side effects or withdrawal of consent.
干预措施: Placebo (Other)
结局指标
主要结局
Percentage of Participants Who Achieved Red Blood Cell (RBC) Transfusion Independence for ≥ 56 Days as Determined by an Independent Review Committee (IRC)
时间窗: From first dose of study drug until 28 days after the last dose, as of the data cut-off date of 17 March 2014; median (minimum, maximum) duration of treatment was 168 (14, 449) and 164 (7, 1158) days in each treatment group respectively.
The percentage of participants who achieved the 56-day RBC transfusion independent (TI) response was defined as the absence of any RBC transfusions during any consecutive "rolling" 56-day interval within the double-blind treatment phase (ie, Days 2 (Day 1 is the first study drug day) to 57, Days 3 to 58, etcetera). The double-blind treatment phase was defined as the period between the 1st dosing up until 28 days after the last study drug dose
Percentage of Participants With a Erythroid Gene Signature Who Achieved RBC Transfusion Independence for ≥ 56 Days as Determined by an Independent Review Committee (IRC)
时间窗: From first dose of study drug until 28 days after the last dose, as of the data cut-off date of 17 March 2014; median (minimum, maximum) duration of treatment was 168 (14, 449) and 164 (7, 1158) days in each treatment group respectively.
The percentage of participants who achieved the 56-day RBC TI response was defined as the absence of any RBC transfusions during any consecutive "rolling" 56-day interval within the double-blind treatment phase (ie, Days 2 (Day 1 is the first study drug day) to 57, Days 3 to 58, etcetera). A participant who achieved at least a 56-day RBC-transfusion-independent response was considered a 56-day RBC-TI responder.
次要结局
- Percentage of Participants Who Achieved an Erythroid Response Based on the Modified International Working Group (IWG) 2006 Criteria(From first dose of study drug until 28 days after the last dose, as of the data cut-off date of 17 March 2014; median (minimum, maximum) duration of treatment was 168 (14, 449) and 164 (7, 1158) days in each treatment group respectively.)
- Number of Participants With Treatment Emergent Adverse Events (TEAE)(From the first dose of study drug through 28 days after discontinuation from the study treatment; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide arm and 529 days in the placebo arm.)
- Percentage of Participants Who Achieved RBC Transfusion Independence With a Duration of ≥ 24 Weeks (168 Days) as Determined by the Sponsor(From first dose of study drug until 28 days after the last dose, as of the data cut-off date of 17 March 2014; median (minimum, maximum) duration of treatment was 168 (14, 449) and 164 (7, 1158) days in each treatment group respectively.)
- Kaplan Meier Estimates of Duration of 56-day RBC Transfusion Independence Response as Determined by the Sponsor(Response was assessed up to the end of treatment; up to the data cut-off date of 17 Mar 2014.)
- Time to 56-Day RBC-Transfusion-Independent (TI) Response as Determined by the Sponsor(From first dose of study drug until 28 days after the last dose of study drug, as of the data cut-off date of 17 March 2014; median (minimum, maximum) duration of treatment was 168 (14, 449) and 164 (7, 1158) days in each treatment group respectively.)
- Kaplan Meier Estimates for Progression to Acute Myeloid Leukemia (AML)(From randomization to final data cut-off date of 03 Jul 2018; median follow up time for progression to AML was 2.3 years (range = 0 to 5.0 years) in the placebo arm and 2.6 years (range = 0 to 6.4 years) in the lenalidomide arm.)
- Kaplan Meier Estimate for Overall Survival (OS)(From randomization to final data cut-off date of 03 July 2018; maximum survival follow up was 6.4 years)
- Compliance Rates Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) From Baseline to Week 48(Baseline, Week 12, (±3 days), Week 24, (±3 days), Week 36, (±3 days), and Week 48 (±3 days); up to data cut-off of 17 Mar 2014)
- Mean Change From Baseline in the EORTC QLQ-C30 Dyspnea Domain at Week 12 and 24(Baseline and Week 12, ±3 days and Week 24, ±3 days)
- Mean Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain at Week 12 and 24(Baseline and Week 12, ±3 days and Week 24, ±3 days)
- Mean Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain at Week 12 and 24(Baseline and Week 12, ±3 days and Week 24, ±3 days)
- Mean Change From Baseline in the Dyspnea Domain Associated With the EORTC QLQ-C-30 Scale at Week 12 and Week 24(Baseline, Week 12, ±3 days and Week 24, ±3 days)
- Mean Change From Baseline in the EORTC QLQ-C30 Fatigue Domain at Week 12 and 24(Baseline and Week 12, ±3 days and Week 24, ±3 days)
- Percentage of Participants With a Clinically Meaningful Improvement in QOL (EORTC QLQ-C-30 Scale) From Baseline in Fatigue Domain at Weeks 12 and 24(Baseline, Week 12, ±3 days and Week 24, ±3 days)
- Percentage of Participants With a Clinically Meaningful Improvement in HRQOL Associated With the EORTC QLQ-C-30 Scale From Baseline in the Dyspnea Domain at Weeks 12 and 24(Baseline, Week 12, ±3 days and Week 24, ±3 days)
- Mean Change From Baseline in the EORTC QLQ-C30 Global Health Status/Quality of Life (QOL) Domain at Week 12 and 24(Baseline and Week 12, ±3 days and Week 24, ±3 days)
- Mean Change From Baseline in Fatigue Domain Associated With the EORTC QLQ-C-30 Scale at Week 12 and Week 24(Baseline, Week 12, ±3 days and Week 24, ±3 days)
- Percentage of Participants With a Clinically Meaningful Improvement in HRQOL Associated With the EORTC QLQ-C-30 Scale From Baseline in the Emotional Functioning Domain at Weeks 12 and 24(Baseline, Week 12, ±3 days and Week 24, ±3 days)
- Healthcare Resource Utilization (HRU): Number of Days of Hospitalization Due to Adverse Events Per Person-Years(From first dose of study drug until 28 days after the last dose, as of the data cut-off date of 17 March 2014; median (minimum, maximum) duration of treatment was 168 (14, 449) and 164 (7, 1158) days in each treatment group respectively.)
- Mean Change From Baseline in the Physical Functioning Domain Associated With the EORTC QLQ-C-30 Scale at Week 12 and Week 24(Baseline, Week 12, ±3 days and Week 24, ±3 days)
- Percentage of Participants With a Clinically Meaningful Improvement in HRQOL Associated With the EORTC QLQ-C-30 Scale From Baseline in the Global Health Status/QOL Domain at Weeks 12 and 24(Baseline, Week 12, ±3 days and Week 24, ±3 days)
- Mean Change From Baseline in the Global Health Status/QoL Domain Associated With the EORTC QLQ-C-30 Scale at Week 12 and Week 24(Baseline, Week 12, ±3 days and Week 24, ±3 days)
- Mean Change From Baseline in the Emotional Functioning Domain Associated With the EORTC QLQ-C30 Scale at Weeks 12 and 24(Baseline, Week 12, ±3 days and Week 24, ±3 days)
- Percentage of Participants With a Clinically Meaningful Improvement in HRQOL Associated With the EORTC QLQ-C-30 Scale From Baseline Within the Physical Functioning Domain at Weeks 12 and 24(Baseline, Week 12, ±3 days and Week 24, ±3 days)
- Healthcare Resource Utilization (HRU): Rate of Inpatient Hospitalizations Related to Adverse Events Per Person Year(From first dose of study drug until 28 days after the last dose, as of the data cut-off date of 17 March 2014; median (minimum, maximum) duration of treatment was 168 (14, 449) and 164 (7, 1158) days in each treatment group respectively.)
- Healthcare Resource Utilization (HRU): Duration of Hospitalizations Due to Adverse Events(From first dose of study drug until 28 days after the last dose, as of the data cut-off date of 17 March 2014; median (minimum, maximum) duration of treatment was 168 (14, 449) and 164 (7, 1158) days in each treatment group respectively.)