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.
Overview
- Phase
- Phase 2
- Intervention
- Lenalidomide
- Conditions
- Myelodysplastic Syndromes
- Sponsor
- Groupe Francophone des Myelodysplasies
- Enrollment
- 132
- Locations
- 48
- Primary Endpoint
- Comparing the efficacy of Lenalidomide alone to Lenalidomide with Epoetin beta in transfusion-dependent ESA-resistant
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief Summary
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.
Detailed Description
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
Investigators
Eligibility Criteria
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
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
Arms & Interventions
Arm A
Lenalidomide 10 mg/day for 21 days every 28 days for 4 courses. 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 cycle 4 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
Intervention: Lenalidomide
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 cycle 4 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
Intervention: Epoetin beta
Outcomes
Primary Outcomes
Comparing the efficacy of Lenalidomide alone to Lenalidomide with Epoetin beta in transfusion-dependent ESA-resistant
Time Frame: After 4 months of treatment
Primary outcome is a complete or partial response defined by the IWG 2006 criteria observed after 4 months of treatment. Comparison in the rate of response between the two groups will be performed with Chi-square test or if necessary Fisher exact test. Same analyzes will be performed with the IWG 2000 response definition .
Secondary Outcomes
- will be to assess the safety of Lenalidomide and of its combination with Epoetin beta(After 2 months of treatment)