A Phase II Open-label, Multicenter, Non Randomized Study Evaluating the Efficacy and the Safety of Clofarabine in Combination With IV Busulfan and Thymoglobulin (CBT) as a Reduced Intensity Conditioning Regimen Prior to Allogeneic Stem Cell Transplantation in Adult Patients With High-risk AML, MDS or ALL.
- Age 18 to 65
- For patients younger than 50 years, cons-indication for the use of a standard
myeloablative conditioning (history of hematopoietic stem cell transplantation
autologous or allogeneic, or the presence of co-morbidities or medical history making
prohibitive in terms toxicity using chemotherapy and / or high dose radiotherapy as
judged by the referring physician) - MDS, ALL or AML at high risk, WHO THE
- Any primary diagnosis of high-risk MDS/AML or ALL eligible for a treatment by reduced
intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation
- Suitable donor available (related or matched unrelated)
- Cardiac: LV Ejection Fraction ≥ 50% by MUGA or Echocardiogram.
- Pulmonary: FEV1 and FVC ≥ 50% predicted, and DLCO (corrected for hemoglobin) ≥ 50% of
- Adequate renal and hepatic function
- Performance status: Karnofsky ≥ 70%
- Informed consent signed by patient prior to enrolment
- Age <18
- Age >65
- Known hypersensitivity to clofarabine or excipients- Other hematologic malignancies
than ALL, AML and MDS
- Patients with prior standard allogeneic HSCT with grade > 2 aGvHD
- Prior standard allogeneic transplantation if < 2 months
- Contra-indication to one of the drug of the RIC regimen .
- Patient with > 3 treatment lines prior to inclusion
- Pregnant or lactating females
- Patient HIV+, Hep B+, Hep C+- Uncontrolled systemic infection
- Performance Status Score ECOG > 2- Known central nervous system involvement with AML
or ALL- Uncontrolled active infection of any kind or bleeding
- Any other severe concurrent disease, or have a history of serious organ dysfunction
or disease involving the heart, kidney, liver or other organ system that may place
the patient at undue risk to undergo the agents included in the conditioning regimen.
- For patients younger than 50 years, possibly indicating a standard myeloablative