Clinical Trial: 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

Study Status: Completed
Recruit Status: Unknown status
Study Type: Interventional

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

Brief Summary: 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.

Detailed Summary:

Patients will receive lenalidomide combined to DNR- AraC chemotherapy. The first 31 patients will receive DNR 45 mg/m2/d, during 3 days, and AraC 200mg/m2/d CI during 7 days.

Progression or not to the next cohort DNR 60 mgm2/d x3d and AraC 200mg/m2d x7d , or on the contrary reduction to the lower cohort DNR 30 mgm2/d x3d and AraC 200mg/m2d x5d will be decided after inclusion of fixed numbers of patients ,after review of toxicity and efficacy by an independent safety review committee (SRC).

Efficacy would be defined as a response rate ≥50%. After inclusion of the first 31 patients, the SRC will choose the cohort dose the last 33 patients will receive, based on toxicity and efficacy criteria.

  1. Induction treatment Lenalidomide 10 mg once daily PO during 3 weeks . DNR 30-45-or 60 mg/m2 /d (depending on the cohort during 3 days (IV push)- AraC 200mg/m2/d during 5- 7 or 7 days (continuous infusion)+ G-CSF (lenograstim): 263 ug/d from day 9, until recovery from aplasia (maximum 30 days).

    Evaluation will be performed after recovery from aplasia, on day 40 at the latest (with marrow aspirate and karyotype).

    Patients in hematological CR, CRi or marrow CR will proceed to consolidation treatment

    :Once the cohort dose has been decided by the SRC, a second cohort of 33 patients will be enrolled

  2. Consolidation treatment (in patients who achieved CR, Cri, or marrow CR) 6 monthly courses of : DNR (at the daily dose required to achieve CR) day1, combined to AraC 60 mg/m2/12h SC
    Sponsor: Groupe Francophone des Myelodysplasies

    Current Primary Outcome: 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 ]

    Original Primary Outcome: Same as current

    Current Secondary Outcome:

    • Duration of response [ Time Frame: At 1 and 2 years ]
    • Progression to AML [ Time Frame: At 1 and 2 years ]
    • Survival and safety of the combination of lenalidomide and chemotherapy [ Time Frame: At 1 and 2 years ]


    Original Secondary Outcome: Same as current

    Information By: Groupe Francophone des Myelodysplasies

    Dates:
    Date Received: April 21, 2009
    Date Started: February 2009
    Date Completion: December 2015
    Last Updated: April 23, 2015
    Last Verified: April 2015