FLUCLORIC - Randomized multicentric Phase III study comparing the efficacy of two reduced intensity conditioning regimens (clofarabine/busulfan versus fludarabine/busulfan) in adults with acute myeloid leukemia and eligible to allogeneic stem cell transplantation: a SFGM-TC study

Prior treatment

• Previous or concurrent second malignancy except for adequately treated basal cell carcinoma of the skin, curatively treated in situ carcinoma of the cervix, curatively treated solid cancer, with no evidence of disease for at least 2 years

Other illness

• HIV positive
• Active Hepatitis B or C
• Uncontrolled infection
• Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule

Lab values

• Left ventricular ejection fraction < 50%
• Creatinine clearance < 50 ml/min (evaluated by MDRD or CKDEPI)
• Serum bilirubine > 30 mmol/l, Cytolysis >5 the upper limit range

Other

• Pro-myelocytic leukemia
• DLCOc <40%
• Uncontrolled haemolytic anaemia
• Participation to another interventional study during the last month or expected participation to another interventional study during participation to the FLUCLORIC study
• 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

• Age ≥ 18 years’ old
• Affiliated with French social security system or beneficiary from such system
• Women must meet one of the following criteria at the time of inclusion: - use adequate contraceptive measures as recommended by the CTFG (Recommendations related to contraception and pregnancy testing in clinical trials v1.1; includes injectable implants, dual hormone birth control pills, intrauterine devices, abstinence from sex, or a sterilized partner), and have a negative pregnancy test (urine or serum pregnancy test) prior to receiving the first dose of study drug; - or be post-menopausal (over 50 years of age with amenorrhea for at least 12 months after discontinuation of all exogenous hormonal therapy) - or (if under 50 years of age) have been amenorrheic for at least 12 months after discontinuation of exogenous hormonal therapy and with luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels corresponding to post-menopausal levels - or have undergone irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy (this operation must be documented). - Contraception methods must be prescribed using effective contraceptive methods during treatment and within 6 months for women of childbearing age (WOCB) and 6 months for men in case they have sexual relations with WOCB after the last dose of Fludarabine/Clofarabine.
• De novo or secondary AML 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 year old with co-morbidity(ies).
• Patient with a related or an unrelated matched donor
• Graft using only peripheral blood stem cells
• Performance status ECOG 0 - 2
• Who provide their written informed consent
• Previous allograft allowed