Relapse remains the main cause of death in patients with myeloid malignancies, especially after an allotransplant. Using drugs with higher anti-leukemic activity as part of the conditioning regimen is one of the strategies to decrease relapse incidence in this population. Retrospective studies have shown that clofarabine can achieve impressive results compared to the use of fludarabine in acute myeloid leukemia (AML) as part of the conditioning regimen. Confirming such results in a prospective manner would definitely establish the CloB2A2 as a superior reduced-intensity conditioning (RIC) regimen compared to the FB2A2 for AML patients.302 AML patients (151 in each arm) in complete remission at transplant will be included with the main objective to demonstrate a significant better 2-year overall survival for CloB2A2 cases (70% vs 55%). A cost-utility analysis and a cost-effectiveness analysis will be also performed as well as an assessment of the quality of life after transplant. Clofarabine will be furnished to all centers. The duration of the study will be 5 years with 3 years of inclusion and 2 years of follow-up for each patient.
De novo or secondary AML (according to ELN 2022 classification) in complete cytological remission at time of transplant (bone marrow blast count < 5%) or MDS/LAM with bone marrow blast count ≤ 5%
Patients in first or second line therapy are allowed
Patient eligible to a RIC regimen : patients aged ≥ 60 year old or <60 with co-morbidity(ies).
Patient with a related or an unrelated matched donor
Pro-myelocytic leukemia
Patient eligible to a myeloablative conditioning regimen
Patient with haploidentical, mismatched unrelated donor or umbilical cord blood
Pregnant or breastfeeding woman or patient refusing contraceptive mesures
Parallel
Fludarabine
Drug30 mg/m2/day IV fludarabine for 5 days (day-6 to day-2)
Busulfan
Drug130 mg/m2/day IV busulfan once daily for 2 days (day -4 and -3)
ATG
DrugThymoglobuline®: 2.5 mg/Kg/day IV for 2 consecutive days (day -2 and -1)
Clofarabine
Drug30 mg/m2/day IV clofarabine for 5 days (day-6 to day-2)
To compare 2-year OS between patients with AML in complete remission receiving either a CloB2A2 or a FB2A2 RIC regimen for allo-SCT.
OS is defined as the time from day 1 of conditioning to death or last follow-up for survivors.
To compare between AML patients in complete remission receiving either a CloB2A2 or a FB2A2 RIC regimen for allo-SCT: Engraftment, primary and secondary graft failure
* Engraftment: PNN \>500/mm3 + donor chimerism \>=5% (day +30/42) * Primary and secondary graft failure: donor chimerism \<5% at day +30/42 post-transplant (primary) or at distance of transplant after achieving engraftment (secondary)
To compare between AML patients in complete remission receiving either a CloB2A2 or a FB2A2 RIC regimen for allo-SCT: Neutrophils and platelet recoveries
* Neutrophils recovery: the first of three consecutive days with neutrophils ≥500/mm3 after aplasia from day 0 of the graft * Platelets recovery: the first of three consecutive days with platelets ≥20000/mm3 without transfusion after aplasia from day 0 of the graft
To compare between AML patients in complete remission receiving either a CloB2A2 or a FB2A2 RIC regimen for allo-SCT: 2-year DFS
DFS: time from day1 of the conditioning to time without death or evidence of relapse or disease progression censored at the date of last follow-up.
To compare between AML patients in complete remission receiving either a CloB2A2 or a FB2A2 RIC regimen for allo-SCT:-2-year relapse incidence
Relapse: any event related to progression or re-occurrence of the disease from day 1 of the conditioning.
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