Transfusion-dependant, low-or intermediate-1-risk myelodysplastic syndromes associated with a deletion 5q cytogenetic abnormality
Conditions
Interventions
Trade Name: Revlimid 5mg, hard capsules
Product Name: Lenalidomide
Product Code: CC-5013
Pharmaceutical Form: Capsule, hard
INN or Propo
Sponsors
Celgene Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Pre-randomization Phase: 1. Must understand and voluntarily sign an informed consent form. 2. Must be =18 years of age at the time of signing the informed consent form 3. Must be able to adhere to the study visit schedule and other protocol requirements. 4. Concurrent corticosteroids used for medical conditions other than MDS is allowed provided subject is on a stable or decreasing dose for =1week prior to study entry 5. Prior thalidomide allowed 6. Documented diagnosis of MDS that meets IPSS criteria for low- to intermediate-1-risk disease and has an associated del 5q[31] cytogenetic abnormality (the deleted chromosomal region must include 5q[31] 7. RBC transfusion-dependent anemia defined as not having any consecutive 56 days without a RBC transfusion within at least the immediate 112 days (4 months). Note: A 112 day documented transfusion history is required for subjects to enter the double-blind phase of the study. Double-blind randomization Phase: As point 1-3, 6 and 7 above, plus: 1. Baseline RBC transfusion requirement has been calculated 2. Female subjects of childbearing potential must: - Understand that the study medication could have a potential teratogenic risk - Agree to use, and be able to comply with, effective contraception without interruption, 28 days before starting study drug, throughout study drug therapy (including dose interruptions) and for 28 days after the end of study drug therapy, even if she has amenorrhoea. This applies unless the subject commits to absolute and continued abstinence confirmed on a monthly basis. The following are effective methods of contraception: implant, Levonorgestrel-releasing intrauterine system, Medroxyprogesterone acetate depot, Tubal sterilisation, Sexual intercourse with a vasectomised male partner only; vasectomy must be confirmed by two negative semen analyses, Ovulation inhibitory progesterone-only pills (i.e., desogestrel). - Agree to have a medically supervised pregnancy test with a minimum sensitivity of 25 IU/ml not more than 3 days from the start of study medication once the subject has been on effective contraception for at least 28 days. This requirement also applies to females of childbearing potential who practice complete and continued abstinence. - Agree to have a medically supervised pregnancy test every 28 days including 28 days after the end of study treatment, except in the case of confirmed tubal sterilization. These tests should be performed not more than 3 days before the start of next treatment. This requirement also applies to females of childbearing potential who practice complete and continued abstinence. 8. Male subjects must: - Agree to use condoms throughout study drug therapy, during any dose interruption and for 7 days after cessation of study therapy if their partner is of childbearing potential and has no contraception. - Agree not to donate semen during study drug therapy and for 7 days after end of study drug therapy. 9. All subjects must: - Agree to abstain from donating blood w
Exclusion criteria
Exclusion criteria: Pre-randomization phase: 1. Pregnant or lactating females. 2. Prior therapy with lenalidomide 3. Proliferative (WBC=12,000/mL) chronic myelomonocytic leukemia (CMML) 4. Prior =grade-2 NCI CTCAE allergic reaction to thalidomide 5. Prior desquamating (blistering) rash while taking thalidomide 6. 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 =3years 7. Use of cytotoxic chemotherapeutic agents or experimental agents (agents that are not commercially available) for the treatment of MDS within 28 days of Day 1 of the Pre-Randomization Phase. 8. Less than 6 months since prior allogeneic bone marrow transplantation of Day 1 of the Pre-Randomization Phase. 9. Less than 3 months since prior autologous bone marrow or stem cell transplantation of Day 1 of the Pre-Randomization Phase. 10. Less than 28 days since prior myelosuppressive anticancer biologic therapy of Day 1 of the Pre-Randomization Phase. 11. Use of erythropoiesis stimulating growth factors (e.g. recombinant human erythropoietin (rHuEPO) within 28 days or long-acting erythropoiesis stimulating growth factor (e.g. darbepoetin) with 56 days of Day 1 of the Pre-Randomization Phase 12. Use of androgens other than to treat hypogonadism is prohibited. 13. Known HIV-1 positivity 14. 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 Double-blind randomization Phase: As points 1-6, 12, 13 and 14 above, plus: 1. Any of the following laboratory abnormalities: - Absolute neutrophil count (ANC) 2.0 mg/dL (177 mmol/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) unless it is clinically due to iron overload from blood transfusions. - Serum total bilirubin > 1.5 mg/dL 2. Clinically significant anemia owing to iron, B12, or folate deficiencies, or autoimmune or hereditary hemolysis or gastrointestinal bleeding (the subject must have a marrow aspirate that is evaluable for storage iron)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: To compare the safety of 2 doses of lenalidomide to that of placebo in subjects with RBC transfusion-dependent low- or intermdiate-1-risk MDS associated with a deletion (del) 5q[31] cytogenetic abnormality.;Primary end point(s): RBC transfusion independence for = 26 weeks (182 days);Timepoint(s) of evaluation of this end point: Up to 52 weeks ;Main Objective: To compare the efficacy of 2 doses of lenalidomide to that of placebo in subjects with red blood cell (RBC) transfusion-dependent low- or intermdiate-1-risk (International Prognosis Scoring System [IPSS]) MDS associated with a deletion (del) 5q[31] cytogenetic abnormality. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 1. Up to 52 weeks 2. Up to 52 weeks 3. Baseline, up to 52 weeks 4. up to 52 weeks 5. up to 52 weeks 6. up to week 52 7. up to 52 weeks 8. up to 52 weeks 9. up to week 52 10. Baseline, Week 12 11. up to 3 years after the last subject has completed/discontinued from the open-label phase 12. up to 3 years after the last subject has completed/discontinued from the open-label phase ; Secondary end point(s): 1.Erythroid response (major and minor according to International MDS Working Group Criteria). 2.Duration of RBC transfusion independence defined to be the number of days between the last transfusion prior to the start of the transfusion-free period and the first transfusion after the transfusion-free period. 3.Change of blood hemoglobin (Hb) concentration from baseline in subjects who achieve a major erythroid response 4.Erythroid response (major and minor according to International MDS Working Group Criteria) at one year. 5.Change in platelet counts from baseline 6.Change in absolute neutrophil counts from baseline 7.Cytogenetic response (according to the International MDS Working Group Criteria) 8.Bone marrow response (according to the International MDS Working Group Criteria) 9.Safety (type, frequency, and severity [National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0] of adverse events (AEs), and relationship of AEs to lenalidomide) 10.Quality of Life (QoL) assessments: [the four components (Physical, Social/Family, Emotional and Functi | — |
Countries
Belgium, France, Germany, Israel, Italy, Spain, Sweden, United Kingdom
Contacts
Public ContactClinicalTrialDisclosure
Celgene Corporation
Outcome results
None listed