Enasidenib and Azacitidine in Treating Patients With Recurrent or Refractory Acute Myeloid Leukemia and IDH2 Gene Mutation

Inclusion Criteria:

• Patients with AML or biphenotypic or bilineage leukemia (including a myeloidcomponent) who have failed prior therapy. Patients with isolated extramedullary AMLare eligible. The World Health Organization (WHO) classification will be used forAML

• Elderly (> 60 years old) patients with newly diagnosed AML not eligible forintensive chemotherapy are also eligible

• AML patients with prior history of myelodysplastic syndrome (MDS) or chronicmyelomonocytic leukemia (CMML) regardless of prior therapy received, are eligible atthe time of diagnosis of AML

• Subjects must have documented IDH2 gene mutation

• Eastern Cooperative Oncology Group (ECOG) performance status =< 3

• Adequate renal function including creatinine < 2 unless related to the disease

• Total bilirubin < 2 x upper limit of normal (ULN) unless increase is due toGilbert's disease or leukemic involvement

• Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) < 3 x ULNunless considered due to leukemic involvement

• Provision of written informed consent

• Oral hydroxyurea and/or cytarabine (up to 2 g/m2) for patients with rapidlyproliferative disease is allowed before the start of study therapy, as needed, forclinical benefit and after discussion with the principal investigator (PI).Concurrent therapy for central nervous system (CNS) prophylaxis or continuation oftherapy for controlled CNS disease is permitted

• Females must be surgically or biologically sterile or postmenopausal (amenorrheicfor at least 12 months) or if of childbearing potential, must have a negative serumor urine pregnancy test within 72 hours before the start of the treatment

• Women of childbearing potential must agree to use an adequate method ofcontraception during the study and until 3 months after the last treatment. Malesmust be surgically or biologically sterile or agree to use an adequate method ofcontraception during the study until 3 months after the last treatment

Exclusion Criteria:

• Patients with t(15;17) karyotypic abnormality or acute promyelocytic leukemia (French-American-British [FAB] class M3-AML)

• Active and uncontrolled comorbidities including active uncontrolled infection,uncontrolled hypertension despite adequate medical therapy, active and uncontrolledcongestive heart failure New York Heart Association (NYHA) class III/IV, clinicallysignificant and uncontrolled arrhythmia as judged by the treating physician

• Any other medical, psychological, or social condition that may interfere with studyparticipation or compliance, or compromise patient safety in the opinion of theinvestigator

• Pregnant or breastfeeding