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 TRANSFUSION-DEPENDENT ANEMIA DUE TO IPSS LOW OR INTERMEDIATE-1 RISK MYELODYSPLASTIC SYNDROMES WITHOUT DELETION 5Q(31) AND UNRESPONSIVE OR REFRACTORY TO ERYTHROPOIESIS-STIMULATING AGENTS
The goal of this clinical research study is to learn if patients with low risk or intermediate-1 risk MDS will need fewer blood transfusions if they take Revlimid® (lenalidomide). Lenalidomide will be compared to a placebo. A placebo is a substance that looks like the study drug but has no active ingredients. The safety of lenalidomide will also be studied.
Disease Group: Leukemia
Treatment Agent: Lenalidomide
Treatment Location: Both at MD Anderson & Community Programs (CCOP/Network)
Estimatated Length of Stay in Houston: NA
Sponsor: Celgene Corporation
Return Visit: Day 1, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 113, 141, 169 and every 28 days (all times are +/- 3 days) while on treatment then every 3 months.
Home Care: Self-medicated
Primary Objective To compare the efficacy of lenalidomide versus placebo in subjects with red blood cell (RBC) transfusion-dependent low or Int-1 risk myelodysplastic syndrome (MDS) associated with any karyotype except deletion 5q and unresponsive or refractory to erythropoiesis stimulating agents in the intent-to-treat (ITT) population and in the pre-specified subgroup of subjects with an erythroid differentiation signature predictive of lenalidomide response. Secondary Objectives To evaluate the safety of lenalidomide versus placebo in subjects with RBC transfusion-dependent low or Int-1 risk MDS associated with any karyotype except deletion 5q and unresponsive or refractory to erythropoiesis-stimulating agents. To evaluate the impact of lenalidomide therapy on health-related quality of life (HRQOL) and healthcare resource utilization.
IRB Review and Approval Date: 06/22/2010
Recruitment Status: Not Accepting
Projected Accrual: 228
1) Must understand and voluntarily sign an informed consent form.
2) Age >/= 18 years at the time of signing the informed consent form.
3) Must be able to adhere to the study visit schedule and other protocol requirements including willingness to undergo bone marrow aspirate and biopsy as indicated in the study protocol.
4) Must be able to complete patient-reported outcome assessments either independently or with minimal assistance of trained clinic personnel or caregiver.
5) Must have a documented diagnosis of MDS associated with the following features: - IPSS low or intermediate-1 risk; - Any karyotype except del 5q  (at least 20 analyzable metaphases are required for standard G-banding cytogenetic analysis at screening).
6) Must have transfusion-dependent anemia that meets the following criteria: - Average transfusion requirement of >/= 2 units/28 days of pRBCs confirmed for a minimum of 112 days immediately preceding randomization. - No consecutive 56 days that was RBC transfusion-free during the 112 days immediately preceding randomization. Hemoglobin levels at the time of or within 7 days prior to transfusions must have been </= 9.0 g/dL for the transfusions to qualify as required for the purpose of providing evidence of transfusion-dependent anemia.
7) Must be unresponsive or refractory to erythropoiesis-stimulating agents, based on one of the following two criteria: - Transfusion-dependence in subjects previously treated with an ESA (requires a minimum ESA trial of >/= 40,000 U/week r-HuEPO x 8 weeks or equivalent dose of darbepoetin), or other erythropoietin agent. Serum erythropoietin level of > 500 mU/mL (measured when Hgb < 9.5 g/dL) in subjects not previously treated with an ESA.
8) Must have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2.
9) Concurrent corticosteroids used for medical conditions other than MDS is allowed provided subject is on a stable or decreasing dose for >/= 1 week prior to randomization.
10) Females of childbearing potential (FCBP) must undergo pregnancy testing and pregnancy results must be negative.
11) Unless practicing complete abstinence from heterosexual intercourse, sexually active FCPB must agree to use adequate contraceptive methods.
12) Males (including those who have had a vasectomy) must use barrier contraception (condoms) when engaging in sexual activity with FCBP.
13) Males must agree not to donate semen or sperm during the duration specified.
14) All subjects must: - Understand that the investigational product could have a potential teratogenic risk. - Agree to abstain from donating blood while taking investigational product and following discontinuation of investigational product - Agree not to share investigational product with another person. - Be counseled about pregnancy precautions and risks of fetal exposure.
1) Any serious medical condition, laboratory abnormality, or psychiatric
illness that would prevent the subject from signing the informed consent form.
2) Pregnant or lactating females.
3) Prior history of malignancies, other than MDS, unless the subject has been free of the disease for >/= 5 years. However, subjects with the following history/concurrent conditions are allowed: o Basal cell carcinoma of the skin o Carcinoma in situ of the cervix o Incidental histologic finding of prostate cancer (Tumor, Node Metastasis (TNM) stage of T1a or T1b)
4) Known Human Immunodeficiency Virus (HIV), active Hepatitis B Virus (HBV) and/or Hepatitis C Virus (HCV) infection.
5) Prior therapy with immunomodulating or immunosuppressive agents, or epigenetic or DNA modulating agents. Subjects who received investigational agents are also excluded.
6) Any of the following laboratory abnormalities: - Absolute neutrophil count (ANC) < 500/muL (0.5 x 10^9/L) - Platelet count < 50,000/muL (50 x 10^9/L) - Serum aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) or alanine transaminase (ALT)/serum glutamate pyruvate transaminase (SGPT) > 3.0 x upper limit of normal (ULN) - serum bilirubin levels > 1.5 x ULN; serum bilirubin levels > 1.5 x ULN are acceptable if these can be attributed to ineffective erythropoiesis.
7) Continued from #6: Subjects with ineffective erythropoiesis may have a decreased haptoglobin level, elevated indirect bilirubin level and/or lactate dehydrogenase level. Autoimmune hemolytic anemia is an exclusion criterion.
8) Renal insufficiency (CrCl < 40 mL/min by Cockroft-Gault method)
9) Uncontrolled hyperthyroidism or hypothyroidism.
10) >/= Grade-2 neuropathy.
11) Use of an erythropoiesis stimulating agent within the 56 days prior to randomization.
12) Prior allogeneic or autologous stem cell transplantation.
13) Concurrent use of androgens other than to treat hypogonadism.
14) Clinically significant anemia due to iron, B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or gastrointestinal bleeding. -- If marrow stain for iron is not available, the transferrin saturation (iron/total iron binding capacity Fe/TIBC) must be >20% or serum ferritin must be >100 ng/dL
15) Prior history of deep venous thrombosis (DVT) or pulmonary embolus (PE) within 3 years of randomization.
16) Significant active cardiac disease within the previous 6 months including: - New York Heart Association class II-IV congestive heart failure - Unstable angina or angina requiring surgical or medical intervention - Myocardial infarction