A Multicenter, Randomized, Double-Blind, Placebo-Controlled, 3-Arm Study of the Efficacy and Safety of 2 Doses of Lenalidomide Versus Placebo in Red Blood Cell (RBC) Transfusion-Dependent Subjects With Low- or Intermediate-1-Risk Myelodysplastic Syndromes Associated With a Deletion (Del) 5q[31] Cytogenetic Abnormality
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 205
- 试验地点
- 38
- 主要终点
- Participants Who Achieved Red Blood Cell (RBC) Transfusion Independence for >= 26 Weeks (182 Days)
研究概览
简要总结
The purpose of this study was to compare 2 doses (10 mg and 5 mg) of lenalidomide to that of placebo in subjects with red blood cell (RBC) transfusion-dependent low- or intermediate-1-risk IPSS MDS associated with a deletion (del) 5q[31] cytogenetic abnormality. Study participants were randomized to one of the two treatment groups or to placebo and took the study drug for 16 weeks. At this timepoint, participants were evaluated for erythroid response. If participants did not achieve at least a minor erythroid response, they were discontinued from the Double-Blind phase and entered into the Open-Label phase. All erythroid responders at Week 16 were to continue in the Double-Blind phase for up to 52 weeks. For participants that were still responding at the end of Double-Blind phase, they could then rollover into the Open-Label phase for an additional two years. Participants could remain on study for up to a total of 3 years. All participants who discontinued from the study were followed every 4 months for overall survival and progression to acute myeloid leukemia (AML).
详细描述
MDS-004 was a multicenter, randomized, double-blind, placebo-controlled, 3-arm study of 2 doses of lenalidomide versus placebo administered to RBC transfusion-dependent adults with low- or intermediate-1 risk MDS associated with a del 5q[31] cytogentetic abnormality. Potential participants that had a del 5q[31] cytogenetic abnormality plus other additional cytogenetic abnormalities were also eligible for enrollment. Transfusion-dependent anemia was defined as documentation that a participant with anemia due to MDS did not have any consecutive 56 days (8 weeks) that were RBC transfusion free during at least the 112 days (16 weeks) prior to Day 1 of the Pre-Randomization Phase.
This study was conducted in three phases:
- a Pre-Randomization Phase
- a Double-Blind Treatment Phase
- an Open-Label Extension Phase
Potentially protocol-eligible participants entered the Pre-Randomization Phase and were evaluated for the inclusion and exclusion criteria for the Double-Blind Treatment Phase. The Pre-Randomization Phase was not to last for more than 56 days (8 weeks). When the participant's baseline RBC transfusion requirement was calculated, and it had been determined that all eligibility criteria had been met, the participant could be randomized for treatment in the Double-Blind Treatment Phase at the time of their next RBC transfusion. This RBC transfusion had to occur within 56 days of the participant's last previous RBC transfusion.
Participants meeting eligibility criteria were randomized (1:1:1 ratio) to receive either lenalidomide 10 mg/day on days 1-21, lenalidomide 5 mg/day on days 1-28, or placebo on days 1-28; all on a 28-day cycle. Randomization was performed using a validated interactive voice response system. Participants were stratified according to karyotype (IPSS karyotype score: 0 vs > 0; i.e., isolated del 5q[31] vs del 5q[31] plus ≥ 1 additional cytogenetic abnormality). A complete blood count (CBC), serum or plasma ferritin, and EPO levels were measured to determine baseline levels.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 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
- •Must understand and voluntarily sign an informed consent form
- •Age 18 years at the time of signing the informed consent form
- •Documented diagnosis of myelodysplastic syndromes (MDS) that meets International Prognostic Scoring System (IPSS) criteria for low to intermediate-1-risk disease and has an associated del 5q(31) cytogenetic abnormality
- •Red blood cell (RBC) transfusion dependent anaemia defined as not having any 56 days without a RBC transfusion within at least the immediate 112 days
- •Must be able to adhere to the study visit schedule and other protocol requirements
- •Women of childbearing potential must have a negative pregnancy test prior to inclusion
排除标准
- •Pregnant or lactating females
- •Prior therapy with lenalidomide
- •Proliferative (white blood cell (WBC)= 12,000/mL) chronic myelomonocytic leukemia (CMML)
- •Prior >= grade-2 (using the National Cancer Institute (NCI)'s Common Terminology Criteria for AEs (CTCAE) (v 3.0)) allergic reaction to thalidomide
- •Prior desquamating (blistering) rash while taking thalidomide
- •Prior history of malignancy other than MDS (except basal cell or squamous cell carcinoma or carcinoma in situ of the cervix or breast) unless the subject has been free of disease for >3 years
- •Use of cytotoxic chemotherapeutic agents or experimental agents (agents that are not commercially available) for the treatment of MDS within 28 days
- •Less than 6 months since prior allogeneic bone marrow transplantation
- •Less than 3 months since prior autologous bone marrow or stem cell transplantation
- •Less than 28 days since prior myelosuppressive anticancer biologic therapy
- •Recombinant human erythropoietin (rHuEPO) therapy received within 28 days
- •Known human immunodeficiency virus (HIV-1) positivity
- •Any serious medical condition or psychiatric illness that will prevent the subject from signing the informed consent form or will place the subject at unacceptable risk if he or she participates in the study
研究组 & 干预措施
Placebo
Placebo matching to active study arms.
干预措施: Placebo (Drug)
Lenalidomide 5 mg
Lenalidomide 5 mg daily 28/28 days
干预措施: Lenalidomide 5 mg (Drug)
Lenalidomide 10 mg
Lenalidomide 10 mg daily 21/28 days
干预措施: Lenalidomide 10 mg (Drug)
结局指标
主要结局
Participants Who Achieved Red Blood Cell (RBC) Transfusion Independence for >= 26 Weeks (182 Days)
时间窗: Up to 52 weeks
The count of study participants who had no RBC transfusions for 26 consecutive weeks or more during the double-blind period.
次要结局
- Participants Who Achieved Red Blood Cell (RBC) Transfusion Independence for 56 Days(Up to 52 weeks)
- Duration of Red Blood Cell (RBC) Transfusion Independence for Participants Who Became RBC Transfusion Independent for at Least 182 Days(up to 3 years)
- Maximum Change From Baseline in Hemoglobin During the Double-blind Period for Participants Who Became Red Blood Cell (RBC) Transfusion Independent for at Least 182 Days(Baseline, up to 52 weeks)
- Participants' Response in Platelet Counts as Defined by the International MDS Working Group (IWG 2000) During Double-blind Period(up to 52 weeks)
- Participants' Response in Absolute Neutrophil Counts as Defined by the International MDS Working Group (IWG 2000) During Double-blind Period(up to week 52)
- Participants' Response Based on Bone Marrow Samples by the International MDS Working Group (IWG 2000) During Double-blind Period(up to 52 weeks)
- Participants Showing Cytogenetic Response by the International MDS Working Group (IWG 2000) During Double-blind Period as Evaluated by Central Review(up to 52 weeks)
- Participants Who Progressed to Acute Myeloid Leukemia (AML) During the Study(up to 3 years)
- Kaplan Meier Estimates of Overall Survival by Randomized Group(up to 3 years)
- Participant Count of Deaths During Double-blind and Open-label by Randomized Group(up to 3 years)
- Change From Baseline in the Functional Assessment of Cancer Therapy-Anemia (FACT-An) Endpoints at Week 12(Baseline, Week 12)
- Change From Baseline in the Trial Outcome Index-Anemia (TOI-An) Endpoints at Week 12(Baseline, Week 12)
- Change From Baseline in the Trial Outcome Index-Fatigue (TOI-F) Endpoints at Week 12(Baseline, Week 12)
- Summary of Participants Who Had Adverse Events (AE) During the Double-blind Period(up to week 52)