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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Celgene Corporation
Roche Pharma AG
Information provided by (Responsible Party):
Groupe Francophone des Myelodysplasies
ClinicalTrials.gov Identifier:
NCT01718379
First received: October 23, 2012
Last updated: March 19, 2014
Last verified: October 2012
  Purpose

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.


Condition Intervention Phase
Myelodysplastic Syndromes
Drug: Lenalidomide
Drug: Epoetin beta
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by Groupe Francophone des Myelodysplasies:

Primary Outcome Measures:
  • Comparing the efficacy of Lenalidomide alone to Lenalidomide with Epoetin beta in transfusion-dependent ESA-resistant [ Time Frame: After 4 months of treatment ] [ Designated as safety issue: Yes ]

    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 [ Time Frame: After 2 months of treatment ] [ Designated as safety issue: Yes ]
    • 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


Estimated Enrollment: 132
Study Start Date: July 2010
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: NEORECORMON

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01718379

  Show 48 Study Locations
Sponsors and Collaborators
Groupe Francophone des Myelodysplasies
Celgene Corporation
Roche Pharma AG
Investigators
Principal Investigator: Andréa TOMA, MD Groupe Francophone des Myelodysplasies
Study Director: François Dreyfus, MD Groupe Francophone des Myelodysplasies
  More Information

No publications provided

Responsible Party: Groupe Francophone des Myelodysplasies
ClinicalTrials.gov Identifier: NCT01718379     History of Changes
Other Study ID Numbers: GFM-Len-Epo-08
Study First Received: October 23, 2012
Last Updated: March 19, 2014
Health Authority: France: ANSM agence nationale de sécuité du médicament et des produits de santé

Keywords provided by Groupe Francophone des Myelodysplasies:
Myelodysplasia

Additional relevant MeSH terms:
Congenital Abnormalities
Myelodysplastic Syndromes
Preleukemia
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Epoetin alfa
Lenalidomide
Thalidomide
Hematinics
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Immunosuppressive Agents
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on August 26, 2014