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 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.