Clofarabine in High Risk Myelodysplastic Syndrome (MDS)

Inclusion Criteria: * Patients aged 18 years or more with MDS according to FAB classification and intermediate-2 or high IPSS risk scores, or CMML (with WBC \< 13 x 109/L and bone marrow blasts \> 10 %) according to WHO classification, or AML according to WHO classification if less than 30 % bone marrow blasts (RAEB-T according to FAB MDS classification or AML according to WHO classification with more than 30 % with bone marrow blasts only if preceded by a proven MDS phase. * Patients previously treated by azacitidine (Vidaza®) in proven progression, or stable after 6 courses with ongoing transfusion dependent anemia (\> 4 RBC units in the 8 weeks preceding inclusion (as erythroid response in IWG 2006 criteria is reduction of at least 4 RBC units in 8 weeks). * Previous biological and or targeted therapies of MDS or AML are allowed if stopped more than 1 month before inclusion. * ECOG PS ≤ 2. * Adequate renal and liver function : i.e. Serum creatinine \< 110 microM in men or 90 microM in women. If plasma creatinine level \< 90 - 110 microM, then the estimated glomerular filtration rate (GFR) must be \< 50 mL/min/1.73 m2 as calculated by the Modification of Diet in Renal Disease (MDRD) equation where Predicted GFR (mL/min/1.73 m2) = 32788 x (plasma creatinine level (microM)-1.154 x (age in years)-0.023 x (0.742 if patient is female) x (1.212 if patient is African American) * Bilirubin \< 1.5 x ULN, (except increased unconjugated bilirubin due to dyserythropoiesis). * Aspartate transaminase (AST)/alanine transaminase (ALT) \< 2.5 × ULN and Alkaline phosphatase \< 2.5 × ULN. * Absence of pregnancy or lactation in female patients (Female patients of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to enrollment). * Male and female patients must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment. * Provided signed written informed consent. * Capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent. Exclusion Criteria: * Patients with AML and bone marrow blasts count of 20-30%, if candidates to intensive AML type chemotherapy. * Known hypersensitivity to clofarabine or excipients. * Concomitant malignant disease. * Active uncontrolled infection (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment). * Concomitant severe cardiovascular disease, i.e. congestive heart failure (NYHA grade \> 3). * Any significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results. * No affiliation to a national insurance scheme directly or to an equivalent system. * Chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol. * Use of investigational agents within 30 days or any anticancer therapy within 2 weeks before study entry with the exception of hydroxyurea. The patient must have recovered from all acute toxicities from any previous therapy.