Safety Study of AG-120 or AG-221 in Combination With Induction and Consolidation Therapy in Participants With Newly Diagnosed Acute Myeloid Leukemia (AML) With an IDH1 and/or IDH2 Mutation

Exclusion Criteria

• •Prior chemotherapy for AML. Hydroxyurea is allowed prior to enrollment for the control of peripheral leukemic blasts in participants with leukocytosis; hydroxyurea may be allowed on study with study Sponsor approval
• •Taking medications with narrow therapeutic windows, unless they can be transferred to other medications prior to enrolling or unless the medications can be properly monitored during the study
• •Taking known strong cytochrome P450 (CYP) 3A4 inducers, unless they can be transferred to other medications prior to enrolling. For participants taking AG-120, systemic administration of a moderate or strong CYP3A4 inhibitor requires careful monitoring of the heart rate-corrected QT interval (QTc) using Fridericia's formula (QTcF)
• •Taking P-glycoprotein (P-gp) or breast cancer resistance protein (BCRP) or OATP1B1/1B3 transporter-sensitive substrate medications unless they can be transferred to alternative medications within ≥5 half-lives prior to administration of AG-221, or unless the medications can be adequately monitored during the study. There are no restrictions regarding the co-administration of such medications with AG-120.
• •Pregnant or breastfeeding
• •Uncontrolled active infection or uncontrolled invasive fungal infection (positive blood or tissue culture). An infection controlled with an approved or closely monitored antibiotic/antifungal treatment is allowed
• •Prior history of malignancy, other than MDS or AML, unless the participant has been free of the disease for ≥1 year prior to the start of study treatment However, participants with the following history/concurrent conditions are allowed: basal or squamous cell carcinoma of the skin; carcinoma in situ of the cervix; carcinoma in situ of the breast; incidental histologic finding of prostate cancer
• •Significant active cardiac disease within 6 months prior to the start of study treatment, including New York Heart Association (NYHA) Class III or IV congestive heart failure; myocardial infarction, unstable angina and/or stroke; or left ventricular ejection fraction (LVEF) \<40% by echocardiogram (ECHO), or by other methods according to institutional practice, obtained within 28 days prior to the start of study treatment
• •QTc interval using Fridericia's formula (QTcF) ≥450 milliseconds (msec) or other factors that increase the risk of QT interval prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome). Bundle branch block and prolonged QTc are permitted with approval of the study Sponsor
• •Taking medications that are known to prolong the QT interval unless they can be transferred to other medications within ≥5 half-lives prior to dosing (If equivalent medication is not available QTc will be closely monitored)
• •Known infection caused by human immunodeficiency virus (HIV) or active hepatitis B or C
• •Dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of orally administered drugs
• •Clinical symptoms suggestive of active central nervous system (CNS) leukemia or known CNS leukemia. Evaluation of cerebrospinal fluid (CSF) during screening is required only if there is a clinical suspicion of CNS involvement by leukemia during screening.
• •Immediate life-threatening, severe complications of leukemia such as uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation
• •Any other medical or psychological condition deemed by the Investigator to be likely to interfere with a participant's ability to give informed consent or participate in the study