A Study of JNJ-75276617 in Combination With Acute Myeloid Leukemia (AML) Directed Therapies

Inclusion Criteria:

Diagnosis of AML according to World Health Organization (WHO) criteria: a) De novo or secondary AML; b) relapsed /refractory (Arm A only); c) harboring NPM1 / KMT2A alterations
Pretreatment clinical laboratory values meeting the following criteria -listed below: White blood cell (WBC) count: less than or equal to <=25 x 10^9 per liter (/L), adequate liver and renal function
ECOG performance status grade of 0, 1 or 2
A woman of childbearing potential must have a negative highly sensitive serum beta-human chorionic gonadotropin at screening and within 48 hours prior to the first dose of study treatment
Must sign an informed consent form (ICF) indicating participant understands the purpose of the study and procedures required for the study and is willing to participate in the study.
Willing and able to adhere to the prohibitions and restrictions specified in this protocol

Exclusion Criteria:

Acute promyelocytic leukemia according to WHO 2016 criteria
Leukemic involvement of the central nervous system
Recipient of solid organ transplant
Cardiovascular disease that is uncontrolled, increases risk for Torsades de Pointes or that was diagnosed within 6 months prior to the first dose of study treatment including, but not limited to:(a) Myocardial infarction; (b) Severe or unstable angina; (c) Clinically significant cardiac arrhythmias, including bradycardia (less than [<] 50 beats per minute); (d) Uncontrolled (persistent) hypertension: (example, blood pressure greater than [>] 140/90 millimeters of mercury [mm Hg]; (e) Acute neurologic events such as stroke or transient ischemic attack, intracranial or subarachnoid hemorrhage, intracranial trauma; (f) Venous thromboembolic events (example, pulmonary embolism) within 1 month prior to the first dose of study treatment (uncomplicated Grade less than or equal to [≤]2 deep vein thrombosis is not considered exclusionary);(g)Congestive heart failure (NYHA class III to IV); (h) Pericarditis or clinically significant pericardial effusion; (i) Myocarditis; (j) Endocarditis (k) Clinically significant hypokalemia, hypomagnesemia, hypocalcemia (corrected for hypoalbuminemia)
Any toxicity (except for alopecia, stable peripheral neuropathy, thrombocytopenia, neutropenia, anemia) from previous anticancer therapy that has not resolved to baseline or to grade 1 or less
Pulmonary compromise that requires the need for supplemental oxygen use to maintain adequate oxygenation