Clinical Trial: Lenalidomide Versus Placebo in Myelodysplastic Syndromes With a Deletion 5q[31] Abnormality

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: 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 Wit

Brief Summary: 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).

Detailed Summary:

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:

  1. a Pre-Randomization Phase
  2. a Double-Blind Treatment Phase
  3. 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-
Sponsor: Celgene Corporation

Current Primary Outcome: Participants Who Achieved Red Blood Cell (RBC) Transfusion Independence for >= 26 Weeks (182 Days) [ Time Frame: 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.


Original Primary Outcome:

Current Secondary Outcome:

  • Participants Who Achieved Red Blood Cell (RBC) Transfusion Independence for 56 Days [ Time Frame: Up to 52 weeks ]
    Count of study participants who had no RBC transfusions during any 56 or more consecutive study days during the double-blind period.
  • Duration of Red Blood Cell (RBC) Transfusion Independence for Participants Who Became RBC Transfusion Independent for at Least 182 Days [ Time Frame: up to 3 years ]
    Mean number of weeks that participants who achieved RBC transfusion independence for at least 182 days were able to maintain RBC transfusion independence. Both double-blind and open-label periods are included.
  • 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 [ Time Frame: Baseline, up to 52 weeks ]
    For participants who became RBC transfusion independent for at least 182 days during the double-blind study period, the mean maximum change from baseline in hemoglobin is summarized.
  • Participants' Response in Platelet Counts as Defined by the International MDS Working Group (IWG 2000) During Double-blind Period [ Time Frame: up to 52 weeks ]
    The International MDS Working Group (IWG) defines a major platelet response for participants with a pre-treatment platelet count of <100,000/mm^3 as an absolute increase of ≥30,000/mm^3 whereas a minor response is defined as a ≥50% increase in platelet count with a net increase greater than 10,000/mm^3 but less than 30,000/mm^3.
  • Participants' Response in Absolute Neutrophil Counts as Defined by the International MDS Working Group (IWG 2000) During Double-blind Period [ Time Frame: up to week 52 ]
    A major neutrophil response is defined by the International MDS Working Group (IWG) criteria as at least a 100% increase, or an absolute increase of ≥500/mm^3 for participants with absolute neutrophil counts (ANC) of less than 1,500/mm^3 before therapy, whichever is greater. A minor response for such participants is defined as an ANC increase of at least 100%, but absolute increase <500/mm^3.
  • Participants' Response Based on Bone Marrow Samples by the International MDS Working Group (IWG 2000) During Double-blind Period [ Time Frame: up to 52 weeks ]
    The IWG criteria for bone marrow improvement: a complete remission is bone marrow sampling showing less than 5% myeloblasts with normal maturation of all cell lines, with no evidence for dysplasia. A partial remission is ≥ 50% decrease in blasts over pre-treatment. Bone marrow progression is a ≥ 50% increase in blasts that exceed the top range of the pretreatment percentile range: a) <5% blasts b) 5-10% blasts c) 10-20% blasts d) 20-30% blasts. For example, a participant with <5% blasts pretreatment with an on study blast increase of 50% which is now >5% showed bone marrow progression.
  • Participants Showing Cytogenetic Response by the International MDS Working Group (IWG 2000) During Double-blind Period as Evaluated by Central Review [ Time Frame: up to 52 weeks ]
    The IWG criteria for evaluating cytogenetic response require a minimum of 20 baseline and post-baseline analyzable metaphases using conventional cytogenetic techniques. A major cytogenetic response is defined as no detectable cytogenetic abnormality if preexisting abnormality was present whereas a minor response requires ≥50% reduction in abnormal metaphases. Progression could be concluded based on as few as 3 metaphases if there were additional abnormalities. The best response is represented.
  • Participants Who Progressed to Acute Myeloid Leukemia (AML) During the Study [ Time Frame: up to 3 years ]
    Number of participants who progressed to acute myeloid leukemia during the study, summarized at three different timepoints: first 16 weeks of the double-blind study, week 52 of the double-blind study, and up to 36 months which includes the double-blind and open-label periods of the study. The counts are cumulative by timeframe.
  • Kaplan Meier Estimates of Overall Survival by Randomized Group [ Time Frame: up to 3 years ]
    Kaplan Meier estimate for median length of survival for study participants as they were randomized at the start of the study.
  • Participant Count of Deaths During Double-blind and Open-label by Randomized Group [ Time Frame: up to 3 years ]
    Count of participant deaths throughout the entire study and reported by the original treatment assignment.
  • Change From Baseline in the Functional Assessment of Cancer Therapy-Anemia (FACT-An) Endpoints at Week 12 [ Time Frame: Baseline, Week 12 ]

    The Functional Assessment of Cancer Therapy-Anemia (FACT-An) questionnaire (Yellen, 1997) was used to assess health-related quality of life (HRQoL).