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  

Acute Myeloid Leukemia Clinical Trial

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

Status Active, not recruiting

Clinical Trial 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.

Clinical Trial Description

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 during 5 days will be given.

Lenalidomide 10 mg/ d during the first 2 weeks of the course.

3. Maintenance treatment Lenalidomide 10 mg/d 2 weeks every month until relapse (dose reduced if cytopenias) In patients still responding after 52 weeks, the drug will continue to be supplied, and follow up until death will be continued in all patients.

SECOND PART OF THE TRIAL AFTER AMENDMENT Treatment schedule of the 2nd Part of the trial

In dose level 4, 20 patients will receive lenalidomide 25 mg/d during 21 days combined to DNR- AraC chemotherapy (DNR 60 mgm2/d x3d and AraC 200mg/m2d x7d) during induction. During consolidation, patients will receive Lenalidomide 25 mg/d during 14 days, combined with DNR 60 mgm2/d x1d and AraC 60 mg/m2 x2/d x5d. finally, during maintenance, patients will receive Lenaidomide 25 mg/d x14d every months, until relapse.

Progression or not to the next cohort (Lenaidomide 50 mg) will be decided after inclusion of 20 patients, after review of toxicity and efficacy by an independent safety review committee (SRC) (Briefly, given median times to reach ANC and platelets > 500 and 50000/mm3, respectively of about 27 days in our previous trial with chemotherapy alone (Gardin, Blood), DLT would be defined by having greater than 3 of 10 patients recovering those levels after more than 40 days, or the occurrence of unexpected grade III-IV non hematological toxicity). Efficacy would be defined as a response rate ≥60%.

In dose level 5, 20 patients will receive lenalidomide 50 mg/d during 21 days combined to DNR- AraC chemotherapy (DNR 60 mgm2/d x3d and AraC 200mg/m2d x7d) during induction. During consolidation, patients will receive Lenalidomide 50 mg/d during 14 days, combined with DNR 60 mgm2/d x1d and AraC 60 mg/m2 x2/d x5d. finally, during maintenance, patients will receive Lenaidomide 50 mg/d x14d every months, until relapse. ;

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Chronic Myelomonocytic Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Leukemia, Myelomonocytic, Acute
• Leukemia, Myelomonocytic, Chronic
• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Preleukemia

• NCT number: NCT00885508
• Study type: Interventional
• Source: Groupe Francophone des Myelodysplasies
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: February 2009
• Completion date: December 2015