A Study of the Efficacy and Safety of Lenalidomide Combined to Escalating Doses of Chemotherapy in Intermediate-2-or High Risk Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML) With Del 5q (GFM-Chimio-Rev)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
Groupe Francophone des Myelodysplasies
ClinicalTrials.gov Identifier:
NCT00885508
First received: April 21, 2009
Last updated: March 18, 2014
Last verified: March 2013
  Purpose

In this trial, the investigators will test the combination of escalating doses of chemotherapy (starting at relatively low dose) with lenalidomide in intermediate-2-or high risk MDS and AML with del 5 q31. It is hoped that this combined therapy will further increase response rate in intermediate-2-or high risk MDS and AML with del 5 q31, without major toxicity in comparison to historical results obtained with chemotherapy alone in the same subset of patients.


Condition Intervention Phase
Myelodysplastic Syndrome
Chronic Myelomonocytic Leukemia
Acute Myeloid Leukemia
Drug: Lenalidomide
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of the Efficacy and Safety of Lenalidomide Combined to Escalating Doses of Chemotherapy in Intermediate-2-or High Risk MDS and AML With Del 5q

Resource links provided by NLM:


Further study details as provided by Groupe Francophone des Myelodysplasies:

Primary Outcome Measures:
  • Response (CR, mCR and Cri, according to IWG criteria for AML and IWG 2006 criteria for MDS) to the combination of lenalidomide and chemotherapy in adult high and int 2 MDS (IPSS) or AML with deletion 5q[31] [ Time Frame: At the end of induction ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Duration of response [ Time Frame: At 1 and 2 years ] [ Designated as safety issue: Yes ]
  • Progression to AML [ Time Frame: At 1 and 2 years ] [ Designated as safety issue: Yes ]
  • Survival and safety of the combination of lenalidomide and chemotherapy [ Time Frame: At 1 and 2 years ] [ Designated as safety issue: Yes ]

Enrollment: 85
Study Start Date: February 2009
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Aracytidine, Daunaurubicine, Lenalidomide Drug: Lenalidomide
  1. Induction treatment Lenalidomide 10 mg once daily PO during 3 weeks . in combination with classical 7+3 chemotherapy.
  2. Consolidation treatment 6 monthly courses of : Lenalidomide 10 mg/ d during the first 2 weeks in combination with classical 5+1 consolidation chemotherapy
  3. Maintenance treatment Lenalidomide 10 mg/d 2 weeks every month until relapse

In absence of toxicity, 20 additionnal patients will be included with lenalidomide dose of 25mg/J, then 20 other additionnals patients with Lenalidomide 50mg/J


  Show Detailed Description

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age ≥ 18 years
  2. Must understand and voluntarily sign an informed consent form
  3. Must be able to adhere to the study visit schedule and other protocol requirements
  4. No contra indication to anthracycline based chemotherapy
  5. Documented diagnosis of MDS, or CMML with WBC < 13,000/mm3 that meets IPSS criteria for intermediate-2 or high-risk disease, or AML with an associated del 5q[31] (the deleted chromosomal region must include 5q[31]), with or without additional cytogenetic abnormalities
  6. Female subjects of childbearing potential must:

    • Understand that the study medication could have a potential teratogenic risk
    • Agree to use, and be able to comply with, effective contraception without interruption, 4 weeks before starting study drug, throughout study drug therapy (including dose interruptions) and for 4 weeks after the end of study drug therapy, even if she has amenorrhoea. This applies unless the subject commits to absolute and continued abstinence confirmed on a monthly basis. The following are effective methods of contraception:

      • Implant, Levonorgestrel-releasing intrauterine system (IUS) (prophylactic antibiotics should be considered at the time of insertion particularly in patients with neutropenia due to risk of infection) , Medroxyprogesterone acetate depot, Tubal sterilization, Ovulation inhibitory progesterone-only pills (i.e., desogestrel), Sexual intercourse with a vasectomised male partner only; vasectomy must be confirmed by two negative semen analyses.
      • Combined oral contraceptive pills are not recommended. If a subject was using combined oral contraception, she must switch to one of the methods above. The increased risk of VTE continues for 4 to 6 weeks after stopping combined oral contraception.
    • Agree to have a medically supervised pregnancy test with a minimum sensitivity of 25 mIU/ml not more than 3 days from the start of study medication once the subject has been on effective contraception for at least 4 weeks. This requirement also applies to women of childbearing potential who practice complete and continued abstinence.
    • Agree to have a medically supervised pregnancy test every 4 weeks including 4 weeks after the end of study treatment, except in the case of confirmed tubal sterilization. These tests should be performed not more than 3 days before the start of next treatment. This requirement also applies to women of childbearing potential who practice complete and continued abstinence
  7. Male subjects must:

    • Agree to use condoms throughout study drug therapy, during any dose interruption and for one week after cessation of study therapy if their partner is of childbearing potential and has no contraception.
    • Agree not to donate semen during study drug therapy and for one week after end of study drug therapy.
  8. All subjects must:

    • Agree to abstain from donating blood while taking study drug therapy and for one week following discontinuation of study drug therapy.
    • Agree not to share study medication with another person and to return all unused study drug to the investigator

Exclusion Criteria:

  1. Pregnant or lactating females.
  2. Contra indication to anthracycline based chemotherapy.
  3. Proliferative (WBC ≥ 13,000/mL) CMML.
  4. Prior ≥ grade-2 NCI CTCAE (v 3.0) allergic reaction to thalidomide.
  5. Prior desquamating (blistering) rash while taking thalidomide.
  6. Prior history of malignancy other than MDS unless the subject has been free of disease for ≥ 5 years.
  7. Use of cytotoxic chemotherapeutic agents or experimental agents (agents that are not commercially available) for the treatment of MDS within 28 days .
  8. Less than 6 months since prior allogeneic bone marrow transplantation.
  9. Less than 3 months since prior autologous bone marrow or stem cell transplantation.
  10. Recombinant human erythropoietin (rHuEPO) therapy received within 28 days.
  11. Known HIV-1 positivity.
  12. Any serious medical condition or psychiatric illness that will prevent the subject from signing the informed consent form or will place the subject at unacceptable risk if he or she participates in the study.
  13. Creatinine Clearance< 50 ml/min
  14. Serum aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) or alanine transaminase (ALT)/serum glutamate pyruvate transaminase (SGPT) > 3.0 x upper limit of normal (ULN)
  15. Serum total bilirubin > 1.5 mg/dL (expect for unconjugated hyperbilirubinemia due to Gilbert's disease or secondary to MDS).
  16. Subjects with ≥ grade-2 neuropathy
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00885508

Locations
France
CH Angers
Angers, France, 49 000
hopital Victor Dupouy
Argenteuil, France, 95107
Centre Hospitalier de La Cote Basque
Bayonne, France, 64100
Hôpital Avicenne
Bobigny, France, 93 000
CHU Haut-Lévèque
Bordeaux, France, 33604
Centre hospitalier de Chambéry
Chambéry, France, 73011
CHU de Clermont-Ferrand
Clermont-Ferrand, France, 63058
Centre henri Mondor
Creteil, France, 94010
Centre Hospitalier du Mans
Le Mans cedex, France, 72037
centre hospitalier de Lens
Lens, France, 62307
Centre Hospitalier de Lens
Lens, France, 32307
Hôpital Limoges
Limoges, France, 87046
Centre Hospitalier Lyon Sud
Lyon, France, 69495
Institut Paoli Calmettes
Marseille, France, 13009
CHU Brabois
Nancy, France, 54511
CHU de nantes
Nantes, France, 44093
Hôpital Archet1
Nice, France, 06202
Hopital Cochin-Hematology
Paris, France, 75679
Hoiptal St Louis
Paris, France, 75475
Centre Hospitalier Joffre
Perpignan, France, 66046
Centre Henri Becquerel
Rouen, France, 76038
Hôpital Hautepierre
Strasbourg, France, 67098
Hopital Purpan Service d'Hématologie Clinique
Toulouse, France, 31059
CH de Valence
Valence, France, 26953
Institut gustave Roussy
Villejuif, France, 94805
Sponsors and Collaborators
Groupe Francophone des Myelodysplasies
Celgene Corporation
Investigators
Principal Investigator: Lionel Adès, MD Groupe Francophone des Myelodysplasies
  More Information

Additional Information:
No publications provided

Responsible Party: Groupe Francophone des Myelodysplasies
ClinicalTrials.gov Identifier: NCT00885508     History of Changes
Obsolete Identifiers: NCT00922298
Other Study ID Numbers: GFM-Chimio-Rev-08
Study First Received: April 21, 2009
Last Updated: March 18, 2014
Health Authority: France: ANSM agence nationale de sécurité du médicament et des produits de santé

Keywords provided by Groupe Francophone des Myelodysplasies:
MDS
AML
deletion 5q
Documented diagnosis of MDS, or CMML
with WBC < 13,000/mm3 that meets IPSS criteria for intermediate-2
or high-risk disease, or AML with an associated del 5q[31]
(the deleted chromosomal region must include 5q[31]),
with or without additional cytogenetic abnormalities

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Leukemia, Myelomonocytic, Chronic
Myelodysplastic Syndromes
Preleukemia
Leukemia, Myelomonocytic, Acute
Neoplasms by Histologic Type
Neoplasms
Myelodysplastic-Myeloproliferative Diseases
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Lenalidomide
Thalidomide
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on August 25, 2014