TRANSFUSION-DEPENDENT ANEMIA DUE TO IPSS LOW OR INTERMEDIATE-1 RISK MYELODYSPLASTIC SYNDROMES WITHOUT DELETION 5Q [31] AND UNRESPONSIVE OR REFRACTORY TO ERYTHROPOIESIS-STIMULATING AGENT MedDRA version: 19.0 Level: LLT Classification code 10068361 Term: MDS System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Revlimid 2.5mg, hard capsules
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: LENALIDOMIDE
CAS Number: 191732-72-6
Concentration unit: mg milligram(s)
Concentration type: equal
Con
Sponsors
Celgene Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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 from trained clinic personnel or caregiver. classification (Brunning, 2008) associated with the following features: - IPSS low or intermediate-1 risk (subjects who were once a higher risk IPSS are excluded) - Any karyotype except del 5q [31] (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), or - Serum erythropoietin level of > 500 mU/mL 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 based on the frequency outlined in Appendices 21.2 and 21.4 and pregnancy results must be negative. 11.Unless practicing complete abstinence from heterosexual intercourse, sexually active FCPB must agree to use adequate contraceptive methods as specified in Appendices 21.2 and 21.4. 12.Males (including those who have had a vasectomy) must use barrier contraception (condoms) when engaging in sexual activity with FCBP as specified Appendices 21.2 and 21.4. 13.Males must agree not to donate semen or sperm during the duration specified in Appendices 21.2 and 21.4. 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 (see Appendices 21.2 and 21.4) - Agree not to share investigational product with another person. - Be counseled about pregnancy precautions and risks of fetal exposure (see Appendices 21.2 and 21.4). Footnote: ¶ Hemoglobin levels = 9.5 g/dL are acceptable if standard practice for clinical management of the subject. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 46 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of
Exclusion criteria
Exclusion criteria: 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: - Basal cell carcinoma of the skin - Carcinoma in situ of the cervix - 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) 3.0 x upper limit of normal (ULN) o serum bilirubin levels > 1.5 x ULN; serum bilirubin levels > 1.5 x ULN are acceptable if these can be attributed to ineffective erythropoiesis. Subjects with ineffective erythropoiesis may have a decreased haptoglobin level, elevated indirect bilirubin level and/or lactate dehydrogenase level (refer to Appendix 21.10). Autoimmune hemolytic anemia is an exclusion criterion. 7. Renal insufficiency (CrCl 20% or serum ferritin must be >100 ng/dL 14. Prior history of deep venous thrombosis (DVT) or pulmonary embolus (PE) within 3 years of randomization. 15. 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the efficacy of lenalidomide versus placebo in subjects with red blood cell (RBC) transfusiondependent low or Int-1 risk MDS associated with any karyotype except deletion 5q[31] and unresponsive or refractory to erythropoiesis-stimulating agents in the ITT population and in the pre-specified subgroup of subjects with an erythroid differentiation signature predictive of lenalidomide response;Secondary Objective: •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[31] and unresponsive or refractory to erythropoiesisstimulating agents. •To evaluate the impact of lenalidomide therapy on health-related quality of life (HRQOL) and healthcare resource utilization.;Primary end point(s): Proportion of subjects in the - ITT population and in the - pre-specified subgroup of subjects with an erythroid differentiation gene expression signature predictive of lenalidomide response (Ebert, 2008) achieving red blood cell (RBC) transfusion independence for at least 8 weeks (using International Working Group (IWG) 2006 criteria);Timepoint(s) of evaluation of this end point: Up to 6 years for each subject (likely to be 6 months to 2 years) | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: See E.5.2;Secondary end point(s): Evaluate the safety of lenalidomide versus placebo. [ Time Frame: at least 6 years from study start through follow-up ] Evaluate the impact of lenalidomide therapy on health-related quality of life (HRQOL) and use of healthcare resources. [ Time Frame: at least 6 years from study start through follow-up ] | — |
Countries
Australia, Austria, Belgium, Czech Republic, France, Germany, Israel, Italy, Poland, Portugal, Spain, Turkey, United Kingdom
Contacts
Public ContactClinicalTrialDisclosure
Celgene Corporation
Outcome results
None listed