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

NCT01718379 | Completed Phase 2

• 1 other identifier: GFM-Len-Epo-08
• Study Type: interventional
• Target: 132
• Locations: 2 countries
• Sites: 48

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.

Conditions

Myelodysplastic Syndromes

Keywords

Myelodysplasia

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• will be to assess the safety of Lenalidomide and of its combination with Epoetin beta

  After 2 months of treatment

Study Arms (2)

Arm A

EXPERIMENTAL

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

Arm B

EXPERIMENTAL

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

Interventions

Lenalidomide DRUG

Lenalidomide:10 mg per day during 21 days

Also known as: Revlimid

Arm A

Epoetin beta DRUG

Epoetin beta: 60,000 Units/week.

Also known as: NEORECORMON

Arm B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Groupe Francophone des Myelodysplasies: lead
• Celgene: collaborator
• Roche Pharma AG: collaborator

Study Sites (48)

Hematology Dpt, Service d'Hématologie Clinique

CHU Albert Michallon, Grenoble, 38043, France

Location

Hematology Dpt, CHR La Source orléans

Orléans, Orléans, 45067, France

Location

Chu Amiens

Amiens, 80054, France

Location

CHU Angers

Angers, 43033, France

Location

Hematology Dpt, CH d'Avignon-305 rue Follereau-

Avignon, 84000, France

Location

CH de la Cote Basque

Bayonne, 64 100, France

Location

centre de Blois

Blois, 41016, France

Location

Hopital Avicenne

Bobigny, 93009, France

Location

Hematology Dpt, CHU Haut-Lévèque

Bordeaux, 33604, France

Location

Hôpital Boulogne Sur Mer

Boulogne-sur-Mer, 62321, France

Location

hôpital Morvan

Brest, 29609, France

Location

CHU Clémenceau

Caen, 14033, France

Location

CH de Carcassonne

Carcassonne, 11890, France

Location

Hematology Dpt, CH René Dubos

Cergy-Pontoise, 95303, France

Location

CHU de Clermont-Ferrand

Clermont-Ferrand, 63058, France

Location

CH de Compiègne

Compiègne, 60321, France

Location

Hematology Dpt, Hôpital Sud Francilien

Corbeil-Essonnes, 91100, France

Location

hopital Henri Mondor

Créteil, 94010, France

Location

CHU de Dijon

Dijon, 21034, France

Location

Hematology Dpt, Hôpital Versailles

Le Chesnay, 78157, France

Location

Hematology Dpt,CH Le mans

Le Mans, 72037, France

Location

CHRU Huriez

Lille, 59037, France

Location

Hopital Saint-Vincent de Paul

Lille, 59160, France

Location

CHRU de Limoges

Limoges, 87046, France

Location

Hematology Dpt, Centre Hospitalier Lyon Sud

Lyon, 69495, France

Location

CH de Mantes-la-jolie

Mantes-la-Jolie, 78201, France

Location

Institut Paoli Calmettes

Marseille, 13009, France

Location

Hematology Dpt, CHU Brabois

Nancy, 54511, France

Location

Hematology Dpt, CHU de nantes

Nantes, 44093, France

Location

Hematology Dpt, CHU Archet

Nice, 06202, France

Location

Hematology Dpt, CHU Caremeau

Nîmes, 30029, France

Location

Hematology Dpt, Hôpital la pitié-Salpétrière

Paris, 75013, France

Location

Hematology Dpt, Hopital Saint Louis

Paris, 75475, France

Location

Hopital Saint Antoine

Paris, 75571, France

Location

centre René Huguenin

Paris Saint Cloud, 92210, France

Location

Hematology Dpt, Hôpital Maréchal Joffre

Perpignan, 66046, France

Location

Hôpital Jean Bernard

Poitiers, 86021, France

Location

Hematology Dpt, Centre Hospitalier de la région d'Annecy

Pringy, 74374, France

Location

CHRU de Reims

Reims, 51092, France

Location

CHU Pontchaillou

Rennes, 35033, France

Location

Centre Henri Becquerel

Rouen, 76038, France

Location

CH de Saint Quentin

Sint Quentin, 02321, France

Location

Chu Strasbourg

Strasbourg, 67098, France

Location

Hematology Dpt, CHU PURPAN

Toulouse, 31059, France

Location

Hematology Dpt, CH CHU Bretoneau

Tours, 37044, France

Location

Hematology Dpt, CHU de Bicêtre

Le Kremlin-Bicêtre, Île-de-France Region, 94275, France

Location

Hematology Dpt, CHU Cochin

Paris, Île-de-France Region, 75679, France

Location

centre hopitalier princesse Grace

Monaco, 98012, Monaco

Location

Related Publications (1)

• 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.

  PMID: 26626993 DERIVED

MeSH Terms

Conditions

Myelodysplastic Syndromes; Anemia, Refractory, with Excess of Blasts

Interventions

Lenalidomide; epoetin beta

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Anemia, Refractory; Anemia

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Andréa TOMA, MD

  Groupe Francophone des Myelodysplasies

  PRINCIPAL INVESTIGATOR

• François Dreyfus, MD

  Groupe Francophone des Myelodysplasies

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 23, 2012
• First Posted: October 31, 2012
• Study Start: July 1, 2010
• Primary Completion: November 1, 2012
• Study Completion: June 1, 2016
• Last Updated: November 8, 2016

Record last verified: 2016-11

Data Sharing

• IPD Sharing: Will not share

Locations

FR (47); MO (1)