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.
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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
735
Clofarabine 30 mg/m2/day IV (2h) on days 2 to 6 (administered as a 2h infusion in 250 ml of 0.9% normal saline solution) Cytarabine 1 g/m2/day intravenous (2h) 4 hours later on days 1 to 5 (administered as a 2h infusion in 250 ml of 5% dextrose in water) G-CSF 5 microg/kg/day intravenous from day 1 to day 6 (administered as a 30 mn infusion in 20 ml of dextrose 5% in water)
Cytarabine 3 g/m2/12h intravenous (3h) on days 1, 3, 5 (administered as a 3h infusion in 250 ml of 5% dextrose in water) G-CSF 5 microg/kg/day intravenous from day 1 to day 5 (administered as a 30 mn infusion in 20 ml of dextrose 5% in water)
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
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.
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.
Time frame: 2 years
• Safety profile of CLARA versus HDAC consolidation courses
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.
Time frame: 2 years
• Possible predictors to response
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))
Time frame: 2 years
• MRD (Minimal Residual Disease) level
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.
Time frame: 2 years
• Overall cumulative incidence of relapse
Time frame: 120 days
• Overall survival (OS)
OS will be defined as the time from diagnosis to death or last contact with the patient
Time frame: 2 years
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Caen, France
Centre Hospitalier René Dubos
Cergy-Pontoise, France
HIA Percy
Clamart, France
Hôpital de Corbeil
Corbeil, France
Hôpital Mondor
Créteil, France
...and 24 more locations