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

Sponsor

French Innovative Leukemia Organisation (Other)

Overall Status

Completed

CT.gov ID

NCT01301820

Collaborator

Celgene Corporation (Industry)

120

Enrollment

Location

Arms

Duration (Months)

4.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia	Drug: azacitidine Drug: Lenalidomide	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

120 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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.

Study Start Date :

Jan 1, 2011

Actual Primary Completion Date :

Feb 1, 2013

Actual Study Completion Date :

Feb 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Other: ARM A 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 azacitidine sc 75 mg/m²/d (d1- d7) Other Names: vidaza®
Other: ARM B 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 lenalidomide 10mg/d (d1- d21) Other Names: revlimid®

Arm

Intervention/Treatment

Other: ARM A

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

azacitidine sc 75 mg/m²/d (d1- d7)

Other Names:

vidaza®

Other: ARM B

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

lenalidomide 10mg/d (d1- d21)

Other Names:

revlimid®

Outcome Measures

Primary Outcome Measures

DFS [18 months]
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.

Secondary Outcome Measures

relapse incidence OS EFS Infectious events [until death]
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.
gene expression and promoter methylation signatures associated with CR [0]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

60 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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