Lenalidomide in Subject With Low and Intermediate-1 Risk MDS and Without Chromosome 5 Abnormality.

A Phase II Study Evaluating the Efficacy/Safety of Lenalidomide With or Without Epoetin Beta in Transfusion-dependent ESA-resistant Patients With IPSS Low- and Intermediate-1 Risk Myelodysplastic Syndromes Without Chromosome 5 Abnormality.

The goal of the present study is to assess, through a randomized phase II trial, the efficacy and safety of Lenalidomide with or without Epoetin beta in transfusion-dependent, ESA-resistant, IPSS low and intermediate-1 risk MDS patients without chromosome 5 abnormality.

Patients will receive either Lenalidomide alone or Lenalidomide and Epoetin beta for 4 months. Responders will be eligible for maintenance treatment with cycles identical to the first cycles, until relapse occurs or until unacceptable toxicity.

This is a multi-center, open-label, randomized, Phase II study.

Patients will be treated either with arm A or B

• Arm A: Lenalidomide 10 mg/day for 21 days every 28 days for 4 courses.
• Arm B: Lenalidomide 10 mg/day for 21 days every 28 days for 4 courses combined with weekly subcutaneous injections of Epoetin beta (60,000 Units/w).

Evaluation of response at the end of 4 months according to IWG 2006 and IWG 2000 criteria.

Maintenance: responders will continue to follow the corresponding treatment arm until relapse occurs; non responders at Evaluation of response at the end of 4 months according to IWG 2006 and IWG 2000 criteria.

in arm A will be considered in failure of treatment and the introduction of Epoetin beta is at the discretion of the physician.

The patients will be followed every 3 months for 12 months

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 (calculate creatinine clearance > 50 ml/min)
• Female subjects of chilbearing potential* must :

Agree to use effective contraception without interruption throughout the study and for at least 4 weeks after the end of treatment

• Men must: Agree to not conceive during the treatment and to use effective contraception during the treatment period (including periods of dose reduction or temporary suspension) and during one week after end of treatment if their partner is of childbearing potential.

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
• Any history of malignancy (other than myelodysplastic syndrome) unless the patient has remained disease free for more than 5 years