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

Phase 2

Completed

• Conditions: Myelodysplastic Syndromes
• Interventions: Drug: Lenalidomide; Drug: Epoetin beta

• Registration Number: NCT01718379
• Lead Sponsor: Groupe Francophone des Myelodysplasies

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

Study Timeline

• Study Start: 2010-07
• Study First Submitted: 2012-10-23
• Study First Submitted QC: 2012-10-29
• Study First Posted: 2012-10-31
• Primary Completion: 2012-11
• Study Completion: 2016-06
• Status Verified: 2016-11
• Last Update Submitted: 2016-11-07
• Last Update Posted: 2016-11-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 132

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A	Lenalidomide	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
Arm B	Epoetin beta	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

Primary Outcome Measures

Name	Time	Method
Comparing the efficacy of Lenalidomide alone to Lenalidomide with Epoetin beta in transfusion-dependent ESA-resistant	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 Outcome Measures

Name	Time	Method
will be to assess the safety of Lenalidomide and of its combination with Epoetin beta	After 2 months of treatment	* 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

Trial Locations

Locations (48)

centre hopitalier princesse Grace; 🇲🇨 Monaco, Monaco

Hopital Saint Antoine; 🇫🇷 Paris, France

CH de la Cote Basque; 🇫🇷 Bayonne, France

hôpital Morvan; 🇫🇷 Brest, France

Chu Strasbourg; 🇫🇷 Strasbourg, France

CH de Saint Quentin; 🇫🇷 Sint Quentin, France

Hematology Dpt, CHU Cochin; 🇫🇷 Paris, Ile de France, France

Chu Amiens; 🇫🇷 Amiens, France

Hematology Dpt, Service d'Hématologie Clinique; 🇫🇷 CHU Albert Michallon, Grenoble, France

CHU Clémenceau; 🇫🇷 Caen, France

Hematology Dpt, CH d'Avignon-305 rue Follereau-; 🇫🇷 Avignon, France

centre de Blois; 🇫🇷 Blois, France

Hematology Dpt, CH René Dubos; 🇫🇷 Cergy-pontoise, France

Hematology Dpt, Centre Hospitalier Lyon Sud; 🇫🇷 Lyon, France

Hematology Dpt, Hopital Saint Louis; 🇫🇷 Paris, France

Hematology Dpt, CHU Caremeau; 🇫🇷 Nimes, France

Hematology Dpt, CHU Brabois; 🇫🇷 Nancy, France

Hematology Dpt, CHU de nantes; 🇫🇷 Nantes, France

centre René Huguenin; 🇫🇷 Paris Saint Cloud, France

Hematology Dpt, Hôpital Maréchal Joffre; 🇫🇷 Perpignan, France

CHRU de Reims; 🇫🇷 Reims, France

Hematology Dpt, CHU de Bicêtre; 🇫🇷 Le Kremlin-Bicêtre, Ile de France, France

CHU Angers; 🇫🇷 Angers, France

Hopital Avicenne; 🇫🇷 Bobigny, France

Hematology Dpt, CHU Haut-Lévèque; 🇫🇷 Bordeaux, France

CHRU Huriez; 🇫🇷 Lille, France

CH de Mantes-la-jolie; 🇫🇷 Mantes-la-jolie, France

Centre Henri Becquerel; 🇫🇷 Rouen, France

Hematology Dpt, CHR La Source orléans; 🇫🇷 Orléans, France

CHRU de Limoges; 🇫🇷 Limoges, France

Institut Paoli Calmettes; 🇫🇷 Marseille, France

CHU de Clermont-Ferrand; 🇫🇷 Clermont-Ferrand, France

Hôpital Boulogne Sur Mer; 🇫🇷 Boulogne Sur Mer, France

Hematology Dpt, CHU PURPAN; 🇫🇷 Toulouse, France

CH de Carcassonne; 🇫🇷 Carcassonne, France

CH de Compiègne; 🇫🇷 Compiègne, France

Hematology Dpt, Hôpital Versailles; 🇫🇷 Le Chesnay, France

Hematology Dpt, Hôpital Sud Francilien; 🇫🇷 Corbeil-essonnes, France

hopital Henri Mondor; 🇫🇷 Créteil, France

CHU de Dijon; 🇫🇷 Dijon, France

Hematology Dpt,CH Le mans; 🇫🇷 Le mans, France

Hopital Saint-Vincent de Paul; 🇫🇷 Lille, France

Hematology Dpt, CH CHU Bretoneau; 🇫🇷 Tours, France

Hematology Dpt, CHU Archet; 🇫🇷 Nice, France

Hematology Dpt, Hôpital la pitié-Salpétrière; 🇫🇷 Paris, France

Hôpital Jean Bernard; 🇫🇷 Poitiers, France

Hematology Dpt, Centre Hospitalier de la région d'Annecy; 🇫🇷 Pringy cedex, France

CHU Pontchaillou; 🇫🇷 Rennes, France