A Phase 3 Multicenter, Open-label, Randomized Study of ASP2215 (Gilteritinib), Combination of ASP2215 Plus Azacitidine and Azacitidine Alone in the Treatment of Newly Diagnosed Acute Myeloid Leukemia with FLT3 Mutation in Patients Not Eligible for Intensive Induction Chemotherapy

Prior treatment

• Subject has received previous therapy for AML, with the exception of the following: ● Emergency leukapheresis, ● Hydroxyurea, ● Preemptive treatment with retinoic acid prior to exclusion of APL ≤ 7 days, ● Growth factor or cytokine support, ● Steroids
• Subject requires treatment with concomitant drugs that are strong inducers of cytochrome P450 (CYP)3A/ P-glycoprotein (P-gp).

Lab values

• Subject with mean Fridericia-corrected QT interval (QTcF) > 480 ms at screening based on central reading.
• Subject with a history of Long QT Syndrome at screening.

Other

• Subject was diagnosed with acute promyelocytic leukemia (APL).
• Subject has BCR-ABL-positive leukemia (chronic myelogenous leukemia in blast crisis).
• Subject has clinically active central nervous system leukemia.

• Subject has a diagnosis of previously-untreated AML according to World Health Organization (WHO) classification [Swerdlow et al, 2008] as determined by pathology review at the treating institution.
• Subject is positive for FLT3 mutation (ITD or TKD [D835/I836] mutation). NOTE: Requirement of FLT3 mutation assessment by central laboratory is only applicable to the randomization portion of the study.
• Subject is ineligible for intensive induction chemotherapy by meeting at least 1 of the following criteria: a. Subject is ≥ 65 years of age and ineligible for intensive induction chemotherapy per investigator’s discretion. b. Subject is ≥ 18 to 64 years of age and has any of the following comorbidities: i. Congestive heart failure (New York Heart Association (NYHA) class ≤ 3) or ejection fraction (EF) ≤ 50%; ii. Creatinine > 2 mg/dL (177 µmol/L), dialysis or prior renal transplant; iii. ECOG performance status ≥ 2; iv. Prior or current malignancy that does not require concurrent treatment; v. Subject has received a cumulative anthracycline dose above 400 mg/m2 of doxorubicin (or cumulative maximum dose of other another anthracycline vi. Known pulmonary disease with decreased diffusion capacity of lung for carbon monoxide (DLCO > 50%) and/or requiring oxygen ≤ 2 liters per minute vii. Any other comorbidity that the physician judges to be incompatible with intensive chemotherapy must be reviewed and approved by the Medical Monitor during screening and before randomization.