A Phase 3 study to test the AG-120 in combination with Azacitidine in comparison with the use of Azacitidine alone in patients ≥ 18 Years of Age with previously untreated Acute Myeloid Leukemia with an IDH1 Mutation

You may be able to join if

• 1. Be ≥18 years of age and meet at least 1 of the following criteria defining ineligibility for intensive induction chemotherapy (IC): a. ≥ 75 years old b. ECOG PS = 2 c. Severe cardiac disorder (eg, congestive heart failure requiring treatment, LVEF ≤50%, or chronic stable angina) d. Severe pulmonary disorder (eg, diffusing capacity of the lungs for carbon monoxide ≤65% or forced expiratory volume in 1 second ≤65%) e. Creatinine clearance <45 mL/minute f. Bilirubin >1.5 times upper limit of normal (× ULN) g. Any other comorbidity that the Investigator judges to be incompatible with intensive IC must be reviewed and approved by the Medical Monitor before study enrollment.
• 10. If female with reproductive potential, must have a negative serum pregnancy test prior to the start of study therapy. Female subjects with reproductive potential are defined as sexually mature women who have not undergone a hysterectomy, bilateral oophorectomy, or tubal occlusion or who have not been naturally postmenopausal for at least 24 consecutive months. Females of reproductive potential, as well as fertile men with female partners of reproductive potential, must use 2 effective forms of contraception (including at least 1 barrier form) from the time of giving informed consent throughout the study and for 90 days (both females and males) following the last dose of study drug(s). Effective forms of contraception are defined as hormonal oral contraceptives, injectables, patches, intrauterine devices, intrauterine hormone-releasing systems, bilateral tubal ligation, condoms with spermicide, or male partner sterilization. Coadministration of AG-120 may decrease the concentrations of hormonal contraceptives.
• 2. Have previously untreated AML, defined according to World Health Organization criteria. Subjects with extramedullary disease alone (ie, no detectable bone marrow and no detectable peripheral blood AML) are not eligible for the study.
• 3. Have an IDH1 mutation resulting in an R132C, R132G, R132H, R132L, or R132S substitution, as determined by central laboratory testing (using an investigational polymerase chain reaction [PCR] assay, Abbott RealTime IDH1) in their bone marrow aspirate (or peripheral blood sample if bone marrow aspirate is not available, with Medical Monitor approval). (Note: Local testing for eligibility and randomization is permitted with Medical Monitor approval; however, results must state an IDH1 mutation resulting in an R132C, R132G, R132H, R132L, or R132S substitution. Bone marrow aspirate [or peripheral blood sample if bone marrow aspirate is not available, with Medical Monitor approval] for central laboratory testing must have been sent with proof of shipment to the central laboratory prior to randomization.)
• 4. Have an ECOG PS score of 0 to 2.
• 5. Have adequate hepatic function, as evidenced by: a. Serum total bilirubin ≤2 × ULN, unless considered to be due to Gilbert’s disease or underlying leukemia, where it must be <3 × ULN. b. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ≤3.0 × ULN, unless considered to be due to underlying leukemia.