Elderly Patients With Acute Myeloid Leukemia (AML), Maintenance Phase After Complete Remission (CR)

Study Overview
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Brief Summary
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Phase II Multicentric Trial Open Label, Multicenter, randomized to evaluate the efficacy of a Maintenance Therapy in First Complete Remission After Induction for Elderly (≥ 60) Fit Patients With Poor Prognosis Acute Myeloid Leukemia (AML). The disease-free survival (DFS) of the patients included in this study will be compared to the ones of the two previously reported groups of patients treated with the same LIA induction therapy

Detailed Description
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The primary objective of this study will be to improve the DFS with an alternate schema combining azacitidine and lenalidomide in elderly fit patients with previously untreated AML and with high risk cytogenetics or secondary AML, who achieved either a complete remission after an LIA induction therapy The secondary objectives will be to determine the relapse incidence, overall survival, event free survival at 1 and 2 years of follow-up, toxicities of the treatment, incidence of infectious events. To define a gene expression and promoter methylation signatures associated with CR and absence of relapse when patients received azacitidine and lenalidomide. Gene promoter methylation and gene expression profiling will be performed at diagnosis, at CR, and after 2 courses of azacitidine and lenalidomide in order to give insight within the mechanisms involved by the use of these 2 drugs and to identify new epigenetic prognostic markers.

Official Title
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Phase II Multicentric Trial Maintenance Therapy With 6 Monthly Revlimid® Cycles Alternated With 6 Monthly Vidaza® Cycles in First CR After Induction LIA Chemotherapy for Elderly Fit Patients With Poor Prognosis Acute Myeloid Leukemia.

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: azacitidine
* Drug: Lenalidomide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cytologically or histologically confirmed acute myeloid leukemia (AML) with : At least 60 years of age and fit for intensive chemotherapy: PS <2 (ECOG) Absence of significant co-morbidities Less than 75 years* of age LAM with high risk features (blasts > 20% in bone marrow) Poor risk cytogenetics Life expectancy > 1 month Affiliated to social security regimen No granulocytic sarcoma as sole site of disease Able and willing to provide written and signed informed consent Exclusion Criteria: Total bilirubin > 2 times upper limit of normal AST and ALT and/or alkaline phosphatase > 4 times upper limit of normal if not in relation with AML. Factor V < 50% without DIC (Disseminated Intravascular Coagulation) NYHA class III or IV congestive heart failure (Echo < 40%, LVEF < 50%),Unstable angina pectoris, Serious cardiac arrhythmia Renal failure not related to AML: serum creatinin > 170 μmol/L or clearance of creatinin ≤ 50 mL/mn Known HIV 1- HIV 2 positivity Prior therapy with azacitidine or lenalidomide Psychiatric illness or social situations that would preclude compliance with study requirements Uncontrolled infection Urgent chemotherapy for DIC, spontaneous tumoral lyse syndrome, leucostase without cytogentic results Women who are pregnant or breastfeeding Women who are unwilling or unable to use an acceptable contraceptive method to avoid pregnancy Men who are unwilling or unable to use an acceptable method of birth control

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: ARM A<br>maintenance study treatment: azacitidine sc 75 mg/m²/d (d1- d7) in first cycle: months 1,3,5,7,9 ,11 then lenalidomide 10mg/d (d1- d21) months 2,4,6,8,10,12 | Drug: azacitidine<br>* azacitidine sc 75 mg/m²/d (d1- d7)<br>* Other names: vidaza®;|
| Other: ARM B<br>maintenance study treatment: lenalidomide 10mg/d (d1- d21)in first cycle and months 1,3,5,7,9 ,11 then azacitidine sc 75 mg/m²/d (d1- d7) months 2,4,6,8,10,12 | Drug: Lenalidomide<br>* lenalidomide 10mg/d (d1- d21)<br>* Other names: revlimid®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DFS | The primary objective of this study will be to improve the DFS with an alternate schema combining azacitidine and lenalidomide in elderly fit patients with previously untreated AML and with high risk cytogenetics or secondary AML, who achieved either a complete remission after an LIA induction therapy. | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| relapse incidence OS EFS Infectious events | The secondary objectives will be to determine the relapse incidence, overall survival, event free survival at 1 and 2 years of follow-up, toxicities of the treatment, incidence of infectious events. | until death | 
| gene expression and promoter methylation signatures associated with CR | To define a gene expression and promoter methylation signatures associated with CR and absence of relapse when patients received azacitidine and lenalidomide. Gene promoter methylation and gene expression profiling will be performed at diagnosis, at CR, and after 2 courses of azacitidine and lenalidomide in order to give insight within the mechanisms involved by the use of these 2 drugs and to identify new epigenetic prognostic markers. | 0 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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maintenance treatment, Disease free survival