Lenalidomide Versus Placebo in Myelodysplastic Syndromes With a Deletion 5q[31] Abnormality
Condition: Myelodysplastic Syndromes
MeSH terms: Preleukemia; Myelodysplastic Syndromes; Congenital Abnormalities; Syndrome
Intervention: Lenalidomide 5 mg; Lenalidomide 10 mg; Placebo
Intervention description: Lenalidomide 5 mg daily 28/28 days; Lenalidomide 10 mg daily 21/28 days; Placebo, matching to active study drug arms
Intervention MeSH terms: Lenalidomide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 205.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: MDS; transfusion dependent; anaemia; cytogenetic abnormality 5q-; erythroid response; leukaemia; CC-5013; Celgene; revlimid; lenalidomide

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).
    

Eligibility criteria:

        Inclusion Criteria:

          -  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

        Exclusion Criteria:

          -  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