A Study of Gilteritinib, Venetoclax and Azacitidine as a Combined Treatment for People Newly Diagnosed With Acute Myeloid Leukemia

Participant has a diagnosis of previously untreated Acute Myeloid Leukemia (AML) according to World Health Organization classification as determined by pathology review at the treating institution.

Participant is positive for FMS-like tyrosine kinase 3 (FLT3) mutation (internal tandem duplication \[ITD\] and/or tyrosine kinase domain \[TKD\] \[D835/I836\] mutation) in bone marrow or whole blood as determined by the central laboratory. A participant with rapidly proliferative disease and unable to wait for the central laboratory results can be enrolled from a local test result.

Participant is ineligible for intensive induction chemotherapy by meeting at least 1 of the following criteria:

* Participant is \>= 75 years of age with Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2.

* Participant is \>= 18 to 75 years of age and has any of the following comorbidities: ECOG performance status 2 or 3, cardiac history of congestive heart failure requiring treatment or ejection fraction \<= 50% or chronic stable angina, known history of diffusion capacity of lung for carbon monoxide (DLCO) \<= 65% or forced expiratory volume in the first second (FEVI) \<= 65%, creatinine clearance \> 30 mL/min to 45 mL/min, calculated by the Cockcroft Gault formula, moderate hepatic impairment with total bilirubin \> 1.5 to \< 3.0 x upper limit of normal (ULN), any other comorbidity incompatible with intensive chemotherapy during screening and before enrollment.

Participant must have a projected life expectancy of at least 12 weeks.

Participant must have adequate organ and bone marrow function prior to enrollment, as specified per protocol's laboratory parameters.

Participant is suitable for oral administration of study drug (gilteritinib and venetoclax) and is willing/able to swallow oral tablets/capsules.

Participant with a known history of human immunodeficiency virus (HIV) on effective antiretroviral therapy must have a viral load undetectable for 6 months prior to Cycle 1 Day 1 (C1D1).

Female participant is eligible to participate if she is not pregnant and at least one of the following conditions apply:

* Not a woman of childbearing potential (WOCBP) OR

* WOCBP agrees to follow the contraceptive guidance starting at screening and continue through the study treatment period, and for at least 180 days after the final study regimen administration.

WOCBP must have a negative pregnancy test during screening.

Female participant must agree not to breastfeed starting at screening, throughout the study treatment period and for 60 days after the last dose of the study treatment regimen.

Female participant must not donate ova starting at screening, throughout the study treatment and for 180 days after the last dose of the study treatment regimen.

Male participant with female partner(s) of childbearing potential must agree to use contraception starting at screening and continue through the study treatment, and for at least 120 days after the last dose of the study treatment regimen.

Male participant must not donate sperm starting at screening, throughout the study treatment and for 120 days after the last dose of the study treatment regimen. (Venetoclax may cause a decrease in spermatogenesis. Male participant considering preservation of fertility should bank sperm before initiating treatment with venetoclax.)

Male participant with a pregnant or breastfeeding partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy or time partner is breastfeeding throughout the treatment period, and for 120 days after the final study drug administration.

Participant agrees not to participate in another interventional study while on treatment in this study.

* For participant with a known history of chronic HBV infection, the HBV viral load must be undetectable on suppressive therapy, if indicated, to be eligible for this study.

Participant has had major surgery within 4 weeks prior to the first study dose.

Participant has a known or suspected hypersensitivity to gilteritinib, azacitidine or venetoclax or any components of the formulations used.

Participant with recent positive test for SARS-CoV-2 ( or diagnosed with COVID-19) and no follow up test with negative result cannot be enrolled. Participant with contact to persons with COVID-19 and participants with signs and symptoms for COVID-19 infection must be tested before enrolling.

Participant who requires concomitant treatment with a strong or moderate P-gp or CYP3A iinhibitor, with the exception of posaconazole, for antifungal prophylaxis during cycle 1 of the Dose Ranging Phase (phase 1). Note: Posaconazole is the only strong CYP3A inhibitor antifungal allowed during the cycle 1 DLT evaluation period. Post-DLT evaluation period, other antifungals including strong or moderate CYP3A inhibitors are allowed throughout the study.

Participant does not have any of the following mutations:

FLT3-ITD, FLT3-TKD/D835 or FLT3-TKD/I836.

What this study is about