Belinostat in Treating Patients With Myelodysplastic Syndromes

Inclusion Criteria: Histologically confirmed myelodysplastic syndromes (MDS) De novo or secondary MDS Patients with < 5 % bone marrow blasts must meet ≥ 1 of the following criteria: Symptomatic anemia with either hemoglobin < 10.0 g/dL or required RBC transfusions within the past 3 months Thrombocytopenia with ≥ 2 platelet counts < 50,000/mm³ or significant hemorrhage requiring platelet transfusions Neutropenia with ≥ 2 absolute neutrophil counts < 1,000/mm³ No acute myeloid leukemia (≥ 20% bone marrow blasts) ECOG performance status 0-2 Life expectancy > 12 weeks Bilirubin ≤ 1.5 times upper limit of normal (ULN) AST ≤ 2 times ULN Creatinine ≤ 2.0 mg/dL Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No history of allergic reactions attributed to compounds of similar chemical or biologic composition to PXD101 No HIV positivity QTc interval ≤ 500 msec No long QT syndrome No significant cardiovascular disease, including any of the following: Unstable angina pectoris Uncontrolled hypertension Congestive heart failure related to primary cardiac disease Condition requiring anti-arrhythmic therapy Ischemic or severe valvular heart disease Myocardial infarction within the past 6 months No other uncontrolled serious medical condition (e.g., cardiac arrhythmias or diabetes) Recovered from prior therapy No more than 2 prior therapies for MDS Prior hematopoietic growth factors, androgens, and other supportive care agents allowed and are not considered in the prior therapy total No prior allogeneic stem cell transplantation More than 4 weeks since prior radiotherapy or chemotherapy (6 weeks for nitrosoureas or mitomycin C) No prior histone deacetylase (HDAC) inhibitors for treatment of MDS More than 2 weeks since prior valproic acid or other HDAC inhibitors No other concurrent investigational agents No concurrent medication that may cause torsades depointes, including any of the following: Disopyramide Dofetilide Ibutilide Procainamide Quinidine Sotalol Bepridil Methadone Amiodarone hydrochloride Arsenic trioxide Cisapride Calcium-channel blockers (e.g., lidoflazine) Anti-infective agents (i.e., clarithromycin, erythromycin, halofantrine, pentamidine, or sparfloxacin) Domperidone or droperidol Antipsychotic agents (i.e., chlorpromazine, haloperidol, mesoridazine, thioridazine, or pimozide)