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

Primary Purpose

Myelodysplastic Syndromes

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Lenalidomide
Epoetin beta
Sponsored by
Groupe Francophone des Myelodysplasies
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Myelodysplastic Syndromes focused on measuring Myelodysplasia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Hematology Dpt, Service d'Hématologie Clinique
  • Hematology Dpt, CHU de Bicêtre
  • Hematology Dpt, CHU Cochin
  • Chu Amiens
  • CHU Angers
  • Hematology Dpt, CH d'Avignon-305 rue Follereau-
  • CH de la Cote Basque
  • centre de Blois
  • Hopital Avicenne
  • Hematology Dpt, CHU Haut-Lévèque
  • Hôpital Boulogne Sur Mer
  • hôpital Morvan
  • CHU Clémenceau
  • CH de Carcassonne
  • Hematology Dpt, CH René Dubos
  • CHU de Clermont-Ferrand
  • CH de Compiègne
  • Hematology Dpt, Hôpital Sud Francilien
  • hopital Henri Mondor
  • CHU de Dijon
  • Hematology Dpt, Hôpital Versailles
  • Hematology Dpt,CH Le mans
  • CHRU Huriez
  • Hopital Saint-Vincent de Paul
  • CHRU de Limoges
  • Hematology Dpt, Centre Hospitalier Lyon Sud
  • CH de Mantes-la-jolie
  • Institut Paoli Calmettes
  • Hematology Dpt, CHU Brabois
  • Hematology Dpt, CHU de nantes
  • Hematology Dpt, CHU Archet
  • Hematology Dpt, CHU Caremeau
  • Hematology Dpt, CHR La Source orléans
  • centre René Huguenin
  • Hematology Dpt, Hôpital la pitié-Salpétrière
  • Hematology Dpt, Hopital Saint Louis
  • Hopital Saint Antoine
  • Hematology Dpt, Hôpital Maréchal Joffre
  • Hôpital Jean Bernard
  • Hematology Dpt, Centre Hospitalier de la région d'Annecy
  • CHRU de Reims
  • CHU Pontchaillou
  • Centre Henri Becquerel
  • CH de Saint Quentin
  • Chu Strasbourg
  • Hematology Dpt, CHU PURPAN
  • Hematology Dpt, CH CHU Bretoneau
  • centre hopitalier princesse Grace

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Arm A

Arm B

Arm Description

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

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

Outcomes

Primary Outcome Measures

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 .

Secondary Outcome Measures

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

Full Information

First Posted
October 23, 2012
Last Updated
November 7, 2016
Sponsor
Groupe Francophone des Myelodysplasies
Collaborators
Celgene, Roche Pharma AG
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1. Study Identification

Unique Protocol Identification Number
NCT01718379
Brief Title
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

2. Study Status

Record Verification Date
November 2016
Overall Recruitment Status
Completed
Study Start Date
July 2010 (undefined)
Primary Completion Date
November 2012 (Actual)
Study Completion Date
June 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Groupe Francophone des Myelodysplasies
Collaborators
Celgene, Roche Pharma AG

4. Oversight

Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myelodysplastic Syndromes
Keywords
Myelodysplasia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
132 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm A
Arm Type
Experimental
Arm Description
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 Title
Arm B
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Lenalidomide
Other Intervention Name(s)
Revlimid
Intervention Description
Lenalidomide:10 mg per day during 21 days
Intervention Type
Drug
Intervention Name(s)
Epoetin beta
Other Intervention Name(s)
NEORECORMON
Intervention Description
Epoetin beta: 60,000 Units/week.
Primary Outcome Measure Information:
Title
Comparing the efficacy of Lenalidomide alone to Lenalidomide with Epoetin beta in transfusion-dependent ESA-resistant
Description
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 .
Time Frame
After 4 months of treatment
Secondary Outcome Measure Information:
Title
will be to assess the safety of Lenalidomide and of its combination with Epoetin beta
Description
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
Time Frame
After 2 months of treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andréa TOMA, MD
Organizational Affiliation
Groupe Francophone des Myelodysplasies
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
François Dreyfus, MD
Organizational Affiliation
Groupe Francophone des Myelodysplasies
Official's Role
Study Director
Facility Information:
Facility Name
Hematology Dpt, Service d'Hématologie Clinique
City
CHU Albert Michallon
State/Province
Grenoble
ZIP/Postal Code
38043
Country
France
Facility Name
Hematology Dpt, CHU de Bicêtre
City
Le Kremlin-Bicêtre
State/Province
Ile de France
ZIP/Postal Code
94275
Country
France
Facility Name
Hematology Dpt, CHU Cochin
City
Paris
State/Province
Ile de France
ZIP/Postal Code
75679
Country
France
Facility Name
Chu Amiens
City
Amiens
ZIP/Postal Code
80054
Country
France
Facility Name
CHU Angers
City
Angers
ZIP/Postal Code
43033
Country
France
Facility Name
Hematology Dpt, CH d'Avignon-305 rue Follereau-
City
Avignon
ZIP/Postal Code
84000
Country
France
Facility Name
CH de la Cote Basque
City
Bayonne
ZIP/Postal Code
64 100
Country
France
Facility Name
centre de Blois
City
Blois
ZIP/Postal Code
41016
Country
France
Facility Name
Hopital Avicenne
City
Bobigny
ZIP/Postal Code
93009
Country
France
Facility Name
Hematology Dpt, CHU Haut-Lévèque
City
Bordeaux
ZIP/Postal Code
33604
Country
France
Facility Name
Hôpital Boulogne Sur Mer
City
Boulogne Sur Mer
ZIP/Postal Code
62321
Country
France
Facility Name
hôpital Morvan
City
Brest
ZIP/Postal Code
29609
Country
France
Facility Name
CHU Clémenceau
City
Caen
ZIP/Postal Code
14033
Country
France
Facility Name
CH de Carcassonne
City
Carcassonne
ZIP/Postal Code
11890
Country
France
Facility Name
Hematology Dpt, CH René Dubos
City
Cergy-pontoise
ZIP/Postal Code
95303
Country
France
Facility Name
CHU de Clermont-Ferrand
City
Clermont-Ferrand
ZIP/Postal Code
63058
Country
France
Facility Name
CH de Compiègne
City
Compiègne
ZIP/Postal Code
60321
Country
France
Facility Name
Hematology Dpt, Hôpital Sud Francilien
City
Corbeil-essonnes
ZIP/Postal Code
91100
Country
France
Facility Name
hopital Henri Mondor
City
Créteil
ZIP/Postal Code
94010
Country
France
Facility Name
CHU de Dijon
City
Dijon
ZIP/Postal Code
21034
Country
France
Facility Name
Hematology Dpt, Hôpital Versailles
City
Le Chesnay
ZIP/Postal Code
78157
Country
France
Facility Name
Hematology Dpt,CH Le mans
City
Le mans
ZIP/Postal Code
72037
Country
France
Facility Name
CHRU Huriez
City
Lille
ZIP/Postal Code
59037
Country
France
Facility Name
Hopital Saint-Vincent de Paul
City
Lille
ZIP/Postal Code
59160
Country
France
Facility Name
CHRU de Limoges
City
Limoges
ZIP/Postal Code
87046
Country
France
Facility Name
Hematology Dpt, Centre Hospitalier Lyon Sud
City
Lyon
ZIP/Postal Code
69495
Country
France
Facility Name
CH de Mantes-la-jolie
City
Mantes-la-jolie
ZIP/Postal Code
78201
Country
France
Facility Name
Institut Paoli Calmettes
City
Marseille
ZIP/Postal Code
13009
Country
France
Facility Name
Hematology Dpt, CHU Brabois
City
Nancy
ZIP/Postal Code
54511
Country
France
Facility Name
Hematology Dpt, CHU de nantes
City
Nantes
ZIP/Postal Code
44093
Country
France
Facility Name
Hematology Dpt, CHU Archet
City
Nice
ZIP/Postal Code
06202
Country
France
Facility Name
Hematology Dpt, CHU Caremeau
City
Nimes
ZIP/Postal Code
30029
Country
France
Facility Name
Hematology Dpt, CHR La Source orléans
City
Orléans
ZIP/Postal Code
45067
Country
France
Facility Name
centre René Huguenin
City
Paris Saint Cloud
ZIP/Postal Code
92210
Country
France
Facility Name
Hematology Dpt, Hôpital la pitié-Salpétrière
City
Paris
ZIP/Postal Code
75013
Country
France
Facility Name
Hematology Dpt, Hopital Saint Louis
City
Paris
ZIP/Postal Code
75475
Country
France
Facility Name
Hopital Saint Antoine
City
Paris
ZIP/Postal Code
75571
Country
France
Facility Name
Hematology Dpt, Hôpital Maréchal Joffre
City
Perpignan
ZIP/Postal Code
66046
Country
France
Facility Name
Hôpital Jean Bernard
City
Poitiers
ZIP/Postal Code
86021
Country
France
Facility Name
Hematology Dpt, Centre Hospitalier de la région d'Annecy
City
Pringy cedex
ZIP/Postal Code
74374
Country
France
Facility Name
CHRU de Reims
City
Reims
ZIP/Postal Code
51092
Country
France
Facility Name
CHU Pontchaillou
City
Rennes
ZIP/Postal Code
35033
Country
France
Facility Name
Centre Henri Becquerel
City
Rouen
ZIP/Postal Code
76038
Country
France
Facility Name
CH de Saint Quentin
City
Sint Quentin
ZIP/Postal Code
02321
Country
France
Facility Name
Chu Strasbourg
City
Strasbourg
ZIP/Postal Code
67098
Country
France
Facility Name
Hematology Dpt, CHU PURPAN
City
Toulouse
ZIP/Postal Code
31059
Country
France
Facility Name
Hematology Dpt, CH CHU Bretoneau
City
Tours
ZIP/Postal Code
37044
Country
France
Facility Name
centre hopitalier princesse Grace
City
Monaco
ZIP/Postal Code
98012
Country
Monaco

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
26626993
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.
Results Reference
derived

Learn more about this trial

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

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