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

Myelodysplastic Syndromes Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01718379
• Other study ID #: GFM-Len-Epo-08
• Status: Completed
• Phase: Phase 2
• First received: October 23, 2012
• Last updated: November 7, 2016
• Start date: July 2010
• Est. completion date: June 2016

Study information

• Verified date: November 2016
• Source: Groupe Francophone des Myelodysplasies
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 132
• Est. completion date: June 2016
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Drug:
• Lenalidomide
Lenalidomide:10 mg per day during 21 days
• Epoetin beta
Epoetin beta: 60,000 Units/week.

Locations

Country	Name	City	State
France	Chu Amiens	Amiens
France	CHU Angers	Angers
France	Hematology Dpt, CH d'Avignon-305 rue Follereau-	Avignon
France	CH de la Cote Basque	Bayonne
France	centre de Blois	Blois
France	Hopital Avicenne	Bobigny
France	Hematology Dpt, CHU Haut-Lévèque	Bordeaux
France	Hôpital Boulogne Sur Mer	Boulogne Sur Mer
France	hôpital Morvan	Brest
France	CHU Clémenceau	Caen
France	CH de Carcassonne	Carcassonne
France	Hematology Dpt, CH René Dubos	Cergy-pontoise
France	Hematology Dpt, Service d'Hématologie Clinique	CHU Albert Michallon	Grenoble
France	CHU de Clermont-Ferrand	Clermont-Ferrand
France	CH de Compiègne	Compiègne
France	Hematology Dpt, Hôpital Sud Francilien	Corbeil-essonnes
France	hopital Henri Mondor	Créteil
France	CHU de Dijon	Dijon
France	Hematology Dpt, Hôpital Versailles	Le Chesnay
France	Hematology Dpt, CHU de Bicêtre	Le Kremlin-Bicêtre	Ile de France
France	Hematology Dpt,CH Le mans	Le mans
France	CHRU Huriez	Lille
France	Hopital Saint-Vincent de Paul	Lille
France	CHRU de Limoges	Limoges
France	Hematology Dpt, Centre Hospitalier Lyon Sud	Lyon
France	CH de Mantes-la-jolie	Mantes-la-jolie
France	Institut Paoli Calmettes	Marseille
France	Hematology Dpt, CHU Brabois	Nancy
France	Hematology Dpt, CHU de nantes	Nantes
France	Hematology Dpt, CHU Archet	Nice
France	Hematology Dpt, CHU Caremeau	Nimes
France	Hematology Dpt, CHR La Source orléans	Orléans
France	Hematology Dpt, CHU Cochin	Paris	Ile de France
France	Hematology Dpt, Hôpital la pitié-Salpétrière	Paris
France	Hematology Dpt, Hopital Saint Louis	Paris
France	Hopital Saint Antoine	Paris
France	centre René Huguenin	Paris Saint Cloud
France	Hematology Dpt, Hôpital Maréchal Joffre	Perpignan
France	Hôpital Jean Bernard	Poitiers
France	Hematology Dpt, Centre Hospitalier de la région d'Annecy	Pringy cedex
France	CHRU de Reims	Reims
France	CHU Pontchaillou	Rennes
France	Centre Henri Becquerel	Rouen
France	CH de Saint Quentin	Sint Quentin
France	Chu Strasbourg	Strasbourg
France	Hematology Dpt, CHU PURPAN	Toulouse
France	Hematology Dpt, CH CHU Bretoneau	Tours
Monaco	centre hopitalier princesse Grace	Monaco

Sponsors (3)

Lead Sponsor	Collaborator
Groupe Francophone des Myelodysplasies	Celgene, Roche Pharma AG

Countries where clinical trial is conducted

France,  Monaco, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	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	Yes