Addition of Vorinostat to Azacitidine in Higher Risk MDS a Phase II add-on Study in Patients With Azacitidine Failure

Inclusion Criteria: * Myelodysplastic syndrome (WHO and FAB classified) including: RA, RARS, RCMD, RCMD-RS RAEB , RAEB-t and CMML with WBC \< 13000/mm3) * IPSS score 1.5 or higher (IPSS intermediate-2 and high risk categories) at the beginning of azacitidine, * Absence of response (CR, PR, marrow CR or HI according to IWG 2006) after a minimum of 6 cycles of azacitidine single agent at 75 mg/m²/d for 7 days per cycle. Patients with a previous dose reduction of AZA may be eligible if the maximum tolerated dose was equal to or above 350mg/m2/cycle (i.e. 50 mg/m²/d for 7 days or 75mg/m2/d for 5 days). * Age more or egal to 18 years * ECOG performance status ≤ 2 (cf. appendix 2); * Patient must have adequate organ function as indicated by the following laboratory values Renal Serum creatinine or calculated creatinine clearancea \< 2 mg/dl OR ≥ 60 mL/min for patients with creatinine levels \> 1.5 X institutional ULN Hepatic Serum total bilirubin ≤ 2.5 X ULN OR direct bilirubin ≤ ULN for patients with total bilirubin levels ≥ 2 mg/dL. AST (SGOT) and ALT (SGPT) ≤ 2.5 times ULN Alkaline Phosphatase ≤ 5 X ULN If \> 2.5 X ULN, then liver fraction should be ≤ 2.5 X ULN a Creatinine clearance should be calculated per institutional standard. * Patient is known to not be refractory to platelet transfusions. * Patient ineligible for allogeneic hematopoietic stem cell transplantation at the time of inclusion in the study * Adherence to the study visit schedule; * Women of childbearing potential must: Agree to use effective contraception without interruption throughout the study and for a further 3 months after the end of treatment; \- Men must: Agree to not conceive during the treatment and to use effective contraception during the treatment period (including periods of dose reduction or temporary suspension) and for a further 3 months after the end of treatment if their partner is of childbearing potential. Agree to learn about the procedures for preservation of sperm. Exclusion Criteria: * Patient had prior treatment with an HDAC inhibitor (e.g., depsipeptide or NSC-630176, MS 275, LAQ-824, PXD-101, LBH589, MGCD0103, CRA024781, etc). Patients who have received compounds with HDAC inhibitor-like activity, such as valproic acid, as anti-tumor therapy should not enroll in this study. Patients who have received such compounds for other indications, e.g. valproic acid for epilepsy, may enroll after a 30-day washout period. * Severe infection or any other uncontrolled severe condition. * Last dose of AZA was given more than 3 months before entering the trial. * Patient already enrolled in another therapeutic trial of an investigational drug * HIV infection or active hepatitis B or C. * Patient has a known allergy or hypersensitivity to any component of vorinostat or azacitidine. * Active cancer, or cancer during the year prior to trial entry other than basal cell carcinoma or carcinoma in situ of the cervix or breast. * Less than 30 days since prior treatment with growth factors (EPO, G-CSF) or non-cytotoxic agents (including low-dose oral chemotherapy); in the event of prior treatment with cytotoxic or demethylating agents, an interval of 3 months is required; * Patient is on any systemic steroids that have not been stabilized to the equivalent of ≤ 10 mg/day prednisone during the 4 weeks prior to the start of the study drugs. * Patients with clinical evidence of CNS leukemia. * Patient has a history of GI surgery or other procedures that might interfere with the absorption or swallowing of the study drugs. * Women who are or could become pregnant, or who are currently breastfeeding * Patient eligible for allotransplantation at the time of inclusion.