Clinical trial NCT01718379: Lenalidomide in Subject With Low and Intermediate-1 Risk MDS and Without Chromosome 5 Abnormality.
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Myelodysplastic Syndromes
Keywords: Myelodysplasia
Lead sponsor: Groupe Francophone des Myelodysplasies
Sponsor class: OTHER
Collaborators: name: Celgene
name: Roche Pharma AG
First posted: 2012-10-31
Enrollment: 132
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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
* 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

Primary outcomes:
measure: Comparing the efficacy of Lenalidomide alone to Lenalidomide with Epoetin beta in transfusion-dependent ESA-resistant
timeFrame: After 4 months of treatment
Secondary outcomes:
measure: will be to assess the safety of Lenalidomide and of its combination with Epoetin beta
timeFrame: After 2 months of treatment
Other outcomes:
Locations:
city: CHU Albert Michallon
country: France
facility: Hematology Dpt, Service d'Hématologie Clinique
state: Grenoble
city: Le Kremlin-Bicêtre
country: France
facility: Hematology Dpt, CHU de Bicêtre
state: Ile de France
city: Paris
country: France
facility: Hematology Dpt, CHU Cochin
state: Ile de France
city: Amiens
country: France
facility: Chu Amiens
city: Angers
country: France
facility: CHU Angers
city: Avignon
country: France
facility: Hematology Dpt, CH d'Avignon-305 rue Follereau-
city: Bayonne
country: France
facility: CH de la Cote Basque
city: Blois
country: France
facility: centre de Blois
city: Bobigny
country: France
facility: Hopital Avicenne
city: Bordeaux
country: France
facility: Hematology Dpt, CHU Haut-Lévèque
city: Boulogne Sur Mer
country: France
facility: Hôpital Boulogne Sur Mer
city: Brest
country: France
facility: hôpital Morvan
city: Caen
country: France
facility: CHU Clémenceau
city: Carcassonne
country: France
facility: CH de Carcassonne
city: Cergy-pontoise
country: France
facility: Hematology Dpt, CH René Dubos
city: Clermont-Ferrand
country: France
facility: CHU de Clermont-Ferrand
city: Compiègne
country: France
facility: CH de Compiègne
city: Corbeil-essonnes
country: France
facility: Hematology Dpt, Hôpital Sud Francilien
city: Créteil
country: France
facility: hopital Henri Mondor
city: Dijon
country: France
facility: CHU de Dijon
city: Le Chesnay
country: France
facility: Hematology Dpt, Hôpital Versailles
city: Le mans
country: France
facility: Hematology Dpt,CH Le mans
city: Lille
country: France
facility: CHRU Huriez
city: Lille
country: France
facility: Hopital Saint-Vincent de Paul
city: Limoges
country: France
facility: CHRU de Limoges
city: Lyon
country: France
facility: Hematology Dpt, Centre Hospitalier Lyon Sud
city: Mantes-la-jolie
country: France
facility: CH de Mantes-la-jolie
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Nancy
country: France
facility: Hematology Dpt, CHU Brabois
city: Nantes
country: France
facility: Hematology Dpt, CHU de nantes
city: Nice
country: France
facility: Hematology Dpt, CHU Archet
city: Nimes
country: France
facility: Hematology Dpt, CHU Caremeau
city: Orléans
country: France
facility: Hematology Dpt, CHR La Source orléans
city: Paris Saint Cloud
country: France
facility: centre René Huguenin
city: Paris
country: France
facility: Hematology Dpt, Hôpital la pitié-Salpétrière
city: Paris
country: France
facility: Hematology Dpt, Hopital Saint Louis
city: Paris
country: France
facility: Hopital Saint Antoine
city: Perpignan
country: France
facility: Hematology Dpt, Hôpital Maréchal Joffre
city: Poitiers
country: France
facility: Hôpital Jean Bernard
city: Pringy cedex
country: France
facility: Hematology Dpt, Centre Hospitalier de la région d'Annecy
city: Reims
country: France
facility: CHRU de Reims
city: Rennes
country: France
facility: CHU Pontchaillou
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Sint Quentin
country: France
facility: CH de Saint Quentin
city: Strasbourg
country: France
facility: Chu Strasbourg
city: Toulouse
country: France
facility: Hematology Dpt, CHU PURPAN
city: Tours
country: France
facility: Hematology Dpt, CH CHU Bretoneau
city: Monaco
country: Monaco
facility: centre hopitalier princesse Grace
Study officials:
affiliation: Groupe Francophone des Myelodysplasies
name: Andréa TOMA, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Groupe Francophone des Myelodysplasies
name: François Dreyfus, MD
role: STUDY_DIRECTOR
References:
citation: 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.