The CLARA Study From the Acute Leukemia French Association (ALFA 0702 Trial)

Phase 2

Completed

• Conditions: Acute Myeloid Leukemia
• Interventions: Drug: HDAc; Drug: CLARA

• Registration Number: NCT00932412
• Lead Sponsor: Hospices Civils de Lyon

Brief Summary

This study is a phase II randomized multicenter study. Patients will be enrolled at time of diagnosis and will receive one or two cycles of induction chemotherapy. Patients, without indication of intensification by allogeneic stem cell transplantation and/or without HLA (Human Leukocyte Antigen)-compatible donor, who attain a CR after one or two cycles of induction chemotherapy, will be eligible for the study Clofarabine / Intermediate-Dose Cytarabine (CLARA)versus High-Dose Cytarabine (HDAC)and will be randomized between 3 courses of CLARA chemotherapy and 3 courses of HDAC chemotherapy as consolidation.

We will compare efficacy and toxicity among the two arms.

Detailed Description

Because of the results of our former trial (ALFA-9802) \[Thomas, 2005\], chemotherapy will be combined in each arm with G-CSF (Granulocyte Colony-Stimulating Factor) given during each sequence of chemotherapy in order to increase the blast priming.

Study Timeline

• Study Start: 2009-03
• Study First Submitted: 2009-07-02
• Study First Submitted QC: 2009-07-02
• Study First Posted: 2009-07-03
• Primary Completion: 2016-04
• Study Completion: 2016-04
• Status Verified: 2016-09
• Last Update Submitted: 2016-09-20
• Last Update Posted: 2016-09-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 735

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
HDAC	HDAc	High-Dose Cytarabine (HDAC) with G-CSF given during each sequence of chemotherapy in order to increase the blast priming.
CLARA	CLARA	Clofarabine / Intermediate-Dose Cytarabine (CLARA) with G-CSF given during each sequence of chemotherapy in order to increase the blast priming.

Primary Outcome Measures

Name	Time	Method
DFS (disease free survival) following first remission achievement (CR : Complete Remission or CRp : Complete Remission but platelet count < 100 x109/L) in younger patients with intermediate-risk or unfavorable-risk AML.	2 years	As all these patients are eligible for allogenic stem cell transplantation in first remission if they have a donor and the comparison of interest primarily concerns non-transplanted patients, it is planned: 1) to exclude patients with an identified donor; 2) to adjust Relapse Free survival (RFS) comparison on the interaction with stem cell transplantation in first remission; and 3) to censure at transplant time the patients allografted before disease progression after randomization (late donor identification) as sensitivity analysis.

Secondary Outcome Measures

Name	Time	Method
• Safety profile of CLARA versus HDAC consolidation courses	2 years	All toxicity encountered during therapy will be evaluated according to the CTC expanded Common Toxicity Criteria and causal relationship to investigational products will be reported.; Serious Adverse Events encountered 3 MONTHS after the last cycle of study chemotherapy (induction/salvage/CLARA/HDAC), whether or not ascribed to the study, will be recorded in the Serious Adverse Event form.
• Possible predictors to response	2 years	Possible predictors to response: with respect to cytogenetics risk groups and mutational status: FLT3 (Fms-like tyrosine kinase 3), MLL (myeloid/ lymphoid or mixed-lineage leukemia), CEBPA (CCAAT / enhancer binding protein α) and NPM(Nucleophosmin))
• MRD (Minimal Residual Disease) level	2 years	Evaluation of MRD in patients with AML in clinical remission is a potentially useful tool for assessing the risk of relapse and guiding further therapeutic decisions. Once an aberrant pattern is identified at diagnosis, it will serve as a "patient-specific probe" to be used, with standard triple/quadruple labelling, to track residual disease longitudinally. Bone marrow and peripheral blood samples for MRD evaluation will be collected at fixed time points: * End of induction in patients achieving CR/CRp.; * End of consolidation 3.; * Every 6 months during follow-up for 2 years.
• Overall cumulative incidence of relapse	120 days
• Overall survival (OS)	2 years	OS will be defined as the time from diagnosis to death or last contact with the patient

Trial Locations

Locations (34)

Hôpital Sud - CHU Amiens; 🇫🇷 Amiens, France

Centre Hospitalier Regional et Universitaire d'Angers; 🇫🇷 Angers, France

Hôpital Victor Dupouy; 🇫🇷 Argenteuil, France

Hôpital Avicenne - bobigny; 🇫🇷 Bobigny, France

Centre Hospitalier Boulogne/Mer; 🇫🇷 Boulogne / Mer, France

Hôpital Clemenceau - chu Caen; 🇫🇷 Caen, France

Centre Hospitalier René Dubos; 🇫🇷 Cergy Pontoise, France

HIA Percy; 🇫🇷 Clamart, France

Hôpital de Corbeil; 🇫🇷 Corbeil, France

Hôpital Mondor; 🇫🇷 Créteil, France

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