LBH589 Plus Decitabine for Myelodysplastic Syndromes (MDS) or Acute Myeloid Leukemia (AML)

Inclusion Criteria:

* AML (except t(15;17), inv(16) or t(8;21) and variants) or high risk MDS (IPSS Int-2 or High) diagnosed according to WHO criteria (see Appendix 1)
* Age ≥ 60 years old
* Not a candidate for allogeneic stem cell transplantation within next 12 weeks
* Ability to provide written informed consent, obtained prior to participation in the study and any related procedures being performed
* Patients must meet the following laboratory criteria:
* Serum albumin ≥ 3 g/dL
* Aspartate aminotransferase (AST)/SGOT and alanine aminotransferase (ALT)/SGPT ≤ 2.5 x upper limit of normal (ULN) ) or ≤ 5.0 x ULN if the transaminase elevation is due to leukemic involvement
* Serum bilirubin ≤ 1.5 x ULN
* Serum creatinine ≤ 1.5 x ULN or 24-hour creatinine clearance ≥ 50 ml/min
* Serum potassium ≥ lower limit of normal (LLN)
* Serum phosphorus ≥ LLN
* Serum total calcium (corrected for serum albumin) or serum ionized calcium ≥ LLN
* Serum magnesium ≥ LLN, thyroid stimulating hormone (TSH) and free thyroxine (T4) within normal limits (WNL) (patients may be on thyroid hormone replacement)
* Baseline MUGA or ECHO must demonstrate left ventricular ejection fraction (LVEF) ≥ the lower limit of the institutional normal.
* Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2

Exclusion Criteria:

* Prior treatment for MDS / AML with Histone deacetylase (HDAC) inhibitor or hypomethylating agent (e.g., Decitabine, azacitidine etc.)
* Active central nervous system (CNS) involvement with MDS/AML
* Impaired cardiac function including any one of the following:
* Screening electrocardiogram (ECG) with a QTc \> 450 msec confirmed by central laboratory prior to enrollment to the study
* Patients with congenital long QT syndrome
* History of sustained ventricular tachycardia
* Any history of ventricular fibrillation or torsades de pointes
* Bradycardia defined as heart rate \< 50 beats per minute. Patients with a pacemaker and heart rate ≥ 50 beats per minute are eligible.
* Patients with a myocardial infarction or unstable angina within 6 months of study entry
* Congestive heart failure (NY Heart Association class III or IV)
* Right bundle branch block and left anterior hemiblock (bifasicular block)
* Uncontrolled hypertension
* Concomitant use of drugs with a risk of causing torsades de pointes
* Patients with unresolved diarrhea \> CTCAE grade 1
* Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral LBH589
* Other concurrent severe and/or uncontrolled medical conditions
* Patients who have received chemotherapy or any investigational drug \< 2 weeks or hydroxyurea \< 48 hours prior to starting study drug or who have not recovered from side effects of such therapy.
* Concomitant use of any anti-cancer therapy or radiation therapy
* Male patients whose sexual partners are women of child bearing potential (WOCBP) not using effective birth control
* Patients with known positivity for human immunodeficiency virus (HIV) or hepatitis C; baseline testing for HIV and hepatitis C is not required
* Patients with any significant history of non-compliance to medical regimens or with inability to grant a reliable informed consent
* Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first LBH589 treatment
* Patients who have received targeted agents within 2 weeks or within 5 half-lives of the agent and active metabolites (whichever is longer) and who have not recovered from side effects of those therapies
* Patients who have undergone major surgery ≤ 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy.