ASP2215: This phase II/III trial is evaluating an oral drug (ASP2215) and a chemotherapy drug (azacitidine), both alone and in combination, for the treatment of Acute Myeloid Leukaemia (AML)A Phase 2/3 Multicenter, Open-label, 3-arm, 2-Stage 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

Inclusion

• Subject is considered an adult according to local regulation at the time of obtaining informed consent.
• 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 (internal tandem duplication [ITD] or tyrosine kinase domain [TKD] [D835/I836] mutation) (or for Korea only: ITD alone or ITD with concurrent TKD activating mutation) in bone marrow or whole blood as determined by central laboratory. Note: Only 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:

  • Subject is ≥ 65 years of age and ineligible for intensive induction chemotherapy.
  • Subject is ≥ 18 to 64 years of age and has any of the following comorbidities: [Ex-US Only]: Congestive heart failure (New York Heart Association {NYHA} class ≤ 3) or ejection fraction (Ef) ≤ 50%; [US Only]: Severe cardiac disorder e.g. congestive heart failure (New York Heart Association [NYHA] class ≤ 3) requiring treatment, ejection fraction ≤ 50%, or chronic stable angina; [Ex-US Only]: Creatinine > 2 mg/dL (177 µmol/L), dialysis or prior renal transplant; [US Only]: Creatinine clearance < 45 mL/min; ECOG performance status ≥ 2;
  • [Ex-US Only]: Known pulmonary disease with decreased diffusion capacity of lung for carbon monoxide (DLCO) and/or requiring oxygen ≤ 2 liters per minute; [US Only] Severe pulmonary disorder (e.g., diffusion capacity of lung for carbon monoxide [DLCO] ≤ 65% or forced expiratory volume in the first second [FEV1] ≤ 65%); Prior or current malignancy that does not require concurrent treatment; Subject has received a cumulative anthracycline dose above 400 mg/m2 of doxorubicin (or cumulative maximum dose of another anthracycline). Any other comorbidity incompatible with intensive chemotherapy must be reviewed and approved by the Medical Monitor during screening and before randomization.

• Subject must meet the following criteria as indicated on the clinical laboratory tests:

  • Serum AST and ALT ≤ 3.0 x Institutional upper limit of normal (ULN)
  • Serum total bilirubin ≤ 1.5 x Institutional ULN
  • Serum potassium ≥ Institutional lower limit of normal (LLN)
  • Serum magnesium ≥ Institutional LLN Repletion of potassium and magnesium levels during the screening period is allowed.
• Subject is suitable for oral administration of study drug.

• Female subject is eligible to participate if female subject is not pregnant and at least one of the following conditions applies:

  • Not a woman of childbearing potential (WOCBP); OR
  • WOCBP agrees to follow the contraceptive guidance starting at screening and continue throughout the study period, and for at least 180 days after the final study drug administration.
• Female subject must agree not to breastfeed starting at screening and throughout the study period, and for 60 days after the final study drug administration.
• Female subject must not donate ova starting at screening and throughout the study period, and for 180 days after the final study drug administration.
• Male subject with female partners of childbearing potential must agree to use contraception as detailed in Contraception Requirements, starting at screening and continue throughout the study period, and for 120 days after the final study drug administration.
• Male subject must not donate sperm starting at screening and throughout the study period and for 120 days after the final study drug administration.
• Subject agrees not to participate in another interventional study while on treatment.