E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Transfusion-dependent, low- or intermediate-1-risk myelodysplastic syndromes associated with a deletion 5q cytogenetic abnormality. |
|
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To compare the efficacy of 2 doses of lenalidomide to that of placebo in subjects with red blood cell (RBC) transfusion-dependent low- or intermediate-1-risk (International Prognostic Scoring System [IPSS]) MDS associated with a deletion (del) 5q[31] cytogenetic abnormality. |
|
E.2.2 | Secondary objectives of the trial |
To compare the safety of 2 doses of lenalidomide to that of placebo in subjects with RBC transfusion-dependent low- or intermediate-1-risk MDS associated with a del 5q[31] cytogenetic abnormality. |
|
E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Study population: 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 ≥ 1 week 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.
Study population: Double-Blind Treatment Phase
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 4. 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]) 5. RBC transfusion-dependent anemia defined as not having any consecutive 56 days without a RBC transfusion within at least the immediate 112-days prior to randomization. 6. Adequate slides of baseline bone marrow aspirate, marrow aspirate iron stain, bone marrow biopsy, and peripheral blood smear have been sent to Central Reviewer 7. Baseline RBC transfusion requirement has been calculated 8. Women of childbearing potential (WCBP) must have a negative serum or urine pregnancy test prior to starting study drug. In addition, sexually active WCBP must agree to use adequate contraceptive methods (oral, injectable, patches, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner) while on study drug. WCBP must agree to have pregnancy tests every 4 weeks while on study drug.
|
|
E.4 | Principal exclusion criteria |
Study population: 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 (v 3.0) 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 ≥ 3 years 7. Use of cytotoxic chemotherapeutic agents or experimental agents (agents that are not commercially available) for the treatment of MDS within 28 days 8. Less than 6 months since prior allogeneic bone marrow transplantation 9. Less than 3 months since prior autologous bone marrow or stem cell transplantation 10. Less than 28 days since prior myelosuppressive anticancer biologic therapy 11. Recombinant human erythropoietin (rHuEPO) therapy received within 28 days 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
Study population: Double-Blind Treatment Phase
1. Pregnant or lactating females 2. Prior therapy with lenalidomide 3. Proliferative (WBC ≥ 12,000/mL) CMML 4. Any of the following laboratory abnormalities: - Absolute neutrophil count (ANC) < 500 cells/mL (0.5 x 109/L) - Platelet count < 25,000/μL (25 x 109/L) - Serum creatinine > 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) - Serum total bilirubin > 1.5 mg/dL 5. Prior ≥ grade-2 NCI CTCAE allergic reaction to thalidomide 6. Prior desquamating (blistering) rash while taking thalidomide 7. Subjects with ≥ grade-2 neuropathy 8. 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) 9. 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 10. Use of androgens other than to treat hypogonadism is prohibited 11. Known HIV-1 positivity 12. 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/she participates in the study
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
RBC transfusion-independence for ≥ 26 weeks (182 days) |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Additional open-label extension phase |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 10 |