SHS_492332 MAWR CAPG 16067

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

The purpose of this study is to determine the efficacy superiority of ASP2215 and/or ASP2215 plus azacitidine versus azacitidine as measured by overall survival (OS) and event-free survival.

Select Inclusion Criteria:

•Considered an adult according to local regulation at the time of obtaining informed consent.
•Diagnosis of previously-untreated AML according to World Health Organization (WHO) classification as determined by pathology review at the treating institution.
•Positive for FLT3 mutation (internal tandem duplication [ITD] or tyrosine kinase domain [TKD] [D835/I836] mutation) in bone marrow or whole blood as determined by central laboratory.
•Ineligible for intensive induction chemotherapy by meeting at least 1 of the following criteria: ≥ 75 years of age; have any of the following comorbidities: congestive heart failure or ejection fraction (Ef) ≤ 50%, creatinine > 2 mg/dL (177 µmol/L), dialysis or prior renal transplant, ECOG performance status ≥ 3, prior or current malignancy that does not require concurrent treatment, or received a cumulative anthracycline dose above 400 mg/m2.
•Must meet the certain laboratory criteria (see protocol for specific values).
•Able to take oral administration of study drug.
•Agrees not to participate in another interventional study while on treatment.

Select Exclusion Criteria:

•Diagnosed as acute promyelocytic leukemia (APL).
•BCR-ABL-positive leukemia (chronic myelogenous leukemia in blast crisis).
•Received previous therapy for AML, with the exception of the following: emergency leukapheresis, hydroxyurea for ≤ 14 days, preemptive treatment with retinoic acid prior to exclusion of APL ≤ 7 days, growth factor or cytokine support, or steroids for the treatment of hypersensitivity or transfusion reactions.
•Clinically active central nervous system leukemia.
•Diagnosed with another malignancy that requires concurrent treatment or hepatic malignancy regardless of need for treatment.
•Clinically significant coagulation abnormality unless secondary to AML.
•Had major surgery within 4 weeks prior to the first study dose.
•Radiation therapy within 4 weeks prior to the first study dose.
•Requires treatment with concomitant drugs that are strong inducers of CYP3A4.
•Requires treatment with concomitant drugs that are strong inhibitors or inducers of P-gp with the exception of drugs that are considered absolutely essential for the care of the subject.
•Requires treatment with concomitant drugs that target serotonin 5HT1R or 5HT2BR or sigma nonspecific receptor with the exception of drugs that are considered absolutely essential for the care of the subject.
•Congestive heart failure classified as New York Heart Association Class IV.
•Mean Fridericia-corrected QT interval (QTcF) > 450 ms at screening based on central reading.
•Long QT Syndrome at screening.
•Known pulmonary disease with diffusion capacity of lung for carbon monoxide (DLCO) ≤ 65%, forced expiratory volume in the first second (FEV1) ≤ 65%, dyspnea at rest or requiring oxygen or any pleural neoplasm.
•Active uncontrolled infection.
Known to have human immunodeficiency virus infection.
Active hepatitis B or C or other active hepatic disorder.
Any condition which makes the subject unsuitable for study participation.
Phase II/III
Raya Mawad, M.D.
Astellas Pharmaceuticals (APUS)
Paul Wisniewski
  • Swedish Medical Center