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.

Study Overview

• Status: Completed
• Conditions: Myelodysplastic Syndromes
• Intervention / Treatment: Drug: Lenalidomide; Drug: Epoetin beta

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 Type: Interventional
• Enrollment (Actual): 132
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Amiens, France, 80054
    • CHU Amiens
  • Angers, France, 43033
    • Chu Angers
  • Avignon, France, 84000
    • Hematology Dpt, CH d'Avignon-305 rue Follereau-
  • Bayonne, France, 64 100
    • CH de la Côte Basque
  • Blois, France, 41016
    • centre de Blois
  • Bobigny, France, 93009
    • Hôpital Avicenne
  • Bordeaux, France, 33604
    • Hematology Dpt, CHU Haut-Lévèque
  • Boulogne Sur Mer, France, 62321
    • Hôpital Boulogne Sur Mer
  • Brest, France, 29609
    • Hopital Morvan
  • Caen, France, 14033
    • CHU Clemenceau
  • Carcassonne, France, 11890
    • Ch de Carcassonne
  • Cergy-pontoise, France, 95303
    • Hematology Dpt, CH René Dubos
  • Clermont-Ferrand, France, 63058
    • CHU de Clermont-Ferrand
  • Compiègne, France, 60321
    • CH de Compiègne
  • Corbeil-essonnes, France, 91100
    • Hematology Dpt, Hôpital Sud Francilien
  • Créteil, France, 94010
    • Hôpital Henri Mondor
  • Dijon, France, 21034
    • CHU de Dijon
  • Le Chesnay, France, 78157
    • Hematology Dpt, Hôpital Versailles
  • Le mans, France, 72037
    • Hematology Dpt,CH Le mans
  • Lille, France, 59037
    • CHRU Huriez
  • Lille, France, 59160
    • Hôpital Saint-Vincent de Paul
  • Limoges, France, 87046
    • CHRU de Limoges
  • Lyon, France, 69495
    • Hematology Dpt, Centre Hospitalier Lyon Sud
  • Mantes-la-jolie, France, 78201
    • CH de Mantes-la-jolie
  • Marseille, France, 13009
    • Institut Paoli Calmettes
  • Nancy, France, 54511
    • Hematology Dpt, CHU Brabois
  • Nantes, France, 44093
    • Hematology Dpt, CHU de nantes
  • Nice, France, 06202
    • Hematology Dpt, CHU Archet
  • Nimes, France, 30029
    • Hematology Dpt, CHU Caremeau
  • Orléans, France, 45067
    • Hematology Dpt, CHR La Source orléans
  • Paris, France, 75571
    • Hopital Saint Antoine
  • Paris, France, 75013
    • Hematology Dpt, Hôpital la pitié-Salpétrière
  • Paris, France, 75475
    • Hematology Dpt, Hopital Saint Louis
  • Paris Saint Cloud, France, 92210
    • Centre René Huguenin
  • Perpignan, France, 66046
    • Hematology Dpt, Hôpital Maréchal Joffre
  • Poitiers, France, 86021
    • Hopital Jean Bernard
  • Pringy cedex, France, 74374
    • Hematology Dpt, Centre Hospitalier de la région d'Annecy
  • Reims, France, 51092
    • CHRU de Reims
  • Rennes, France, 35033
    • CHU Pontchaillou
  • Rouen, France, 76038
    • Centre Henri Becquerel
  • Sint Quentin, France, 02321
    • CH de Saint Quentin
  • Strasbourg, France, 67098
    • CHU Strasbourg
  • Toulouse, France, 31059
    • Hematology Dpt, CHU PURPAN
  • Tours, France, 37044
    • Hematology Dpt, CH CHU Bretoneau
  • Grenoble
    • CHU Albert Michallon, Grenoble, France, 38043
      • Hematology Dpt, Service d'Hématologie Clinique
  • Ile de France
    • Le Kremlin-Bicêtre, Ile de France, France, 94275
      • Hematology Dpt, CHU de Bicêtre
    • Paris, Ile de France, France, 75679
      • Hematology Dpt, CHU Cochin
• Monaco
  • Monaco, Monaco, 98012
    • centre hopitalier princesse Grace

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: Lenalidomide; Lenalidomide:10 mg per day during 21 days; Other Names: Revlimid
Experimental: 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	Drug: Epoetin beta; Epoetin beta: 60,000 Units/week.; Other Names: NEORECORMON

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparing the efficacy of Lenalidomide alone to Lenalidomide with Epoetin beta in transfusion-dependent ESA-resistant	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 .	After 4 months of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
will be to assess the safety of Lenalidomide and of its combination with Epoetin beta	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	After 2 months of treatment

Collaborators and Investigators

• Sponsor: Groupe Francophone des Myelodysplasies
• Collaborators: Roche Pharma AG; Celgene
• Investigators: Principal Investigator: Andréa TOMA, MD, Groupe Francophone des Myelodysplasies; Study Director: François Dreyfus, MD, Groupe Francophone des Myelodysplasies

Publications and helpful links

General Publications

• Chesnais V, Renneville A, Toma A, Lambert J, Passet M, Dumont F, Chevret S, Lejeune J, Raimbault A, Stamatoullas A, Rose C, Beyne-Rauzy O, Delaunay J, Solary E, Fenaux P, Dreyfus F, Preudhomme C, Kosmider O, Fontenay M; Groupe Francophone des Myelodysplasies. Effect of lenalidomide treatment on clonal architecture of myelodysplastic syndromes without 5q deletion. Blood. 2016 Feb 11;127(6):749-60. doi: 10.1182/blood-2015-04-640128. Epub 2015 Dec 1.

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (Actual): November 1, 2012
• Study Completion (Actual): June 1, 2016

Study Registration Dates

• First Submitted: October 23, 2012
• First Submitted That Met QC Criteria: October 29, 2012
• First Posted (Estimate): October 31, 2012

Study Record Updates

• Last Update Posted (Estimate): November 8, 2016
• Last Update Submitted That Met QC Criteria: November 7, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: Myelodysplasia
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Preleukemia; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Lenalidomide
• Other Study ID Numbers: GFM-Len-Epo-08

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No