This study is to evaluate the safety and tolerability of vorinostat in combination with decitabine as well as the in vivo molecular and biological effects of vorinostat in patients with refractory or relapsed Acute Myelogenous Leukemia (AML) and intermediate or high risk as defined by International Prognostic Scoring System (IPSS) Myelodysplastic Syndrome (MDS). Participants with Acute Myelogenous Leukemia or Myelodysplastic Syndrome are eligible.

Inclusion Criteria:

• Patient is at least 18 years old with refractory/relapsed AML

  • If untreated AML, patient is older than 60 years old and not a candidate for standard chemotherapy

• Patient is at least 4 weeks from prior treatment and has recovered from all prior treatment side effects

• Patient has no known liver or kidney problems

• Patient knows of no reason they can not receive transfusions of blood clotting cells (platelets)

• Patient is able to swallow capsules

• Patients both male and female are willing to practice birth control during the study

Exclusion Criteria:

• Patient has received prior treatment with valproic acid, decitabine or azacitidine
• Being is less than 18 years of age or if patient has untreated AML is below 60 years of age
• Patient is a women who is pregnant or breastfeeding. Patient has an active infection that requires antibiotics
• Patient has uncontrolled illness including but not limited to the following: heart problems (congestive heart failure, unstable angina pectoris, cardiac arrhythmia), inflammation of the pancreas; a mental or social condition that may interfere with patient following study procedures
• Patient has known human immunodeficiency virus (HIV) infection or HIV-related malignancy. Patient has a known history of hepatitis B or C infection
• Patient currently has another active cancer other than certain types of skin cancer
• Patient is heterosexual and able to have a child and is unwilling to practice birth control during the study