Entinostat and Azacitidine in Treating Older Patients with Acute Myeloid Leukemia

Inclusion Criteria

• One of the following: * Untreated AML in (de novo or treatment related) patients of age >= 60 years in the following categories: ** Medical conditions that compromise the ability to give cytotoxic chemotherapy as the primary modality ** Patients who decline cytotoxic chemotherapy * Patients with AML of age >= 60 years who have relapsed despite one prior regimen
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
• Patients must not have untreated active infections at the time of study entry
• Creatinine < 2 mg/dl
• Total serum bilirubin within institutional limits unless due to hemolysis, Gilbert’s syndrome, or ineffective erythropoiesis
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal
• Life expectancy of at least 3 months
• Patients must be informed of the investigational nature of the treatment, results that might be expected, and potential toxicities; they must be able to understand and give informed written consent according to federal and institutional guidelines
• Declined or ineligible for potentially curative options such as allogeneic stem cell transplant
• No chemotherapy or study drugs for > 3 weeks prior to starting study
• Women of childbearing potential should be advised to avoid becoming pregnant and men should be advised to not father a child while receiving treatment; all men and women of childbearing potential must use acceptable methods of birth control throughout the study as described below; females of childbearing potential: recommendation is for 2 effective contraceptive methods during the study; adequate forms of contraception are double-barrier methods (condoms with spermicidal jelly or foam and diaphragm with spermicidal jelly or foam), oral, depo Provera, or injectable contraceptives, intrauterine devices, and tubal ligation; male patients with female partners who are of childbearing potential: recommendation is for male and partner to use at least 2 effective contraceptive methods, as described above, during the study or to abstain

Exclusion Criteria

• Any of the Following: * Treatment for AML, including hematopoietic growth factors, < 3 weeks prior to study registration; exception: hydroxyurea may be administered to patients with white blood cell (WBC) > 30,000/uL * Radiotherapy < 4 weeks prior to study registration * Failure to recover (to < grade 1) from all adverse events associated with prior therapy * Valproic acid < 2 weeks prior to study registration * Hypersensitivity to azacytidine, deoxyazacytidine, mannitol, entinostat or components of the entinostat tablet * Any advanced malignant hepatic tumor(s)
• Prior therapy with demethylating agents within the last four months
• Clinical evidence of central nervous system (CNS) or pulmonary leukostasis, disseminated intravascular coagulation, or CNS leukemia
• Serious or uncontrolled medical conditions
• Concurrent use of any other investigational agents
• Known human immunodeficiency virus- (HIV) positive patients
• Pregnancy or breast feeding
• Male and female patients who are fertile who do not agree to use an effective barrier methods of birth control (i.e. abstinence) to avoid pregnancy during the study and for a minimum of 30 days after study treatment