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

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.

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

Study Overview

• Status: Completed
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: azacitidine; Drug: Lenalidomide

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 Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Angers, France, 49033
    • Mathilde HUNAULT BERGER

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / 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®

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: French Innovative Leukemia Organisation
• Collaborators: Celgene Corporation
• Investigators: Principal Investigator: Mathilde HUNAULT BERGER, MD PD, French Innovative Leukemia Organisation

Publications and helpful links

Helpful Links

• FILO website

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): February 1, 2013
• Study Completion (Actual): February 1, 2013

Study Registration Dates

• First Submitted: February 4, 2011
• First Submitted That Met QC Criteria: February 22, 2011
• First Posted (Estimate): February 23, 2011

Study Record Updates

• Last Update Posted (Estimate): March 16, 2016
• Last Update Submitted That Met QC Criteria: March 15, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: maintenance treatment; Disease free survival
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Lenalidomide; Azacitidine
• Other Study ID Numbers: LAMSA-maintenance Rev-5Aza

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No