E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
patients with IPSS low- and intermediate-1 risk myelodysplastic syndromes without chromosome 5 abnormality |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028533 |
E.1.2 | Term | Myelodysplastic syndrome |
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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 |
Erythroid response rate after 4 courses, assessed according to IWG 2006 criteria
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E.2.2 | Secondary objectives of the trial |
•Safety of Lenalidomide and of its combination with Epoetin beta: adverse events (type, frequency, severity) and relationship of adverse events to study drug •% of major HI-E and minor HI-E after 4 courses according to IWG 2000 criteria •Erythroid response duration •Time to response •Time to progression according to IPSS •RBC transfusion independence •Prognostic factors of response •Survival •Quality of life |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
MDS defined as •Low or int-1 IPSS score •Documented absence of chromosome 5 abnormality (del(5q) or -5 karyotype) •De novo MDS, excluding therapy-related MDS AND •Transfusion dependance (requirement of at least 4 units of RBC transfusions every 8 weeks ) •Resistance or loss of response to a previous treatment with Epoetin alpha/beta (at least 60,000 Units/w) or Darbepoetin (at least 250 µg/w), for at least 12 weeks •Ineligibility for allogeneic stem cell transplantation or intensive chemotherapy during the next 12 months •ECOG performance status ≤ 2 •Age ≥ 18 years •Life expectancy ≥ 3 months •Adequate liver function (transaminases serum levels ≤ 3N) •Adequate renal function (ca lculate creatinine clearance > 50 ml/min)
•Female subjects of chilbearing potential* must : -Understand the study drug is expected to have a teratogenic risk. -Understand that even if she has amenorrhea, she must follow all the advice on effective contraception. -She understands the potential consequences of pregnancy and the need to rapidly consult if there is a risk of pregnancy
•Male patients taking lenalidomide must : -Agree the use of a condom if engaged in sexual activity with a woman of childbearing potential, during the entire period of treatment, even if dysruption of treatment and during one week after end of treatment. -Agree not to donate semen during study drug therapy and for one week after end of study drug therapy.
•All subjects must : -Agree to abstain from donating blood while taking study drug therapy and for one week following discontinuation of study drug therapy. -Agree not to share study medication with another person and to return all unused study drug to the investigator.
•Signed informed consent prior to start of any study-specific procedures •Ability to participate to a clinical trial and adhere to study procedures
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E.4 | Principal exclusion criteria |
•Active serious infection not controlled by oral or intravenous antibiotics •Platelets less than 50 G/L •Prior history of deep vein thrombosis or pulmonary embolism •Previous treatment by Thalidomide •Treatment with any investigational antileukemic agent or chemotherapy at least 6 weeks prior to study entry and lack of full recovery from side effects due to prior therapy independent of when that therapy were given •Rapidely progressive disease with copromised organ function judged to be life-threatening by the Investigator •Pregnant or lactating female •Known human immunodeficiency virus (HIV) infection •Known active hepatitis B and/or C virus infection •Hypersensitivity or intolerance to Lenalidomide or any of the excipients •Hypersensitivity to Epoetin beta or any of the excipients •Uncontrolled arterial hypertension
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of the trial will be to compare the efficacy of Lenalidomide to Lenalidomide with Epoetin beta in ESA-resistant MDS by evaluating the erythroid response rate according to the IWG 2006 response criteria at 4 months of therapy |
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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 | Yes |
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 | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
•Arm A: Lenalidomide / Arm B: Lenalidomide combined of epoetin beta |
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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.8.4.1 | Number of sites anticipated in Member State concerned | 33 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |