The goal of this clinical trial is to learn if Venetoclax+Azacytidine+Quizartinib works better than standard therapy (Venetoclax+Azacytdine) to treat naïve adult patients with acute myeloid leukemia (AML) who are not suitable for standard induction therapy due to age, co-morbidities or other risk factors. The main question it aims to answer is:
\- Does the combination of Venetoclax+Azacytidine+Quizartinib show more probability of overall survival than Venetoclax+Azacytdine?
Researchers will compare Venetoclax+Azacytidine+Quizartinib to Venetoclax+Azacytdine to see if Venetoclax+Azacytidine+Quizartinib works better than Venetoclax+Azacytdine to treat AML.
Participants will be randomized to one of the two treatment arms in a 1:1 ratio, both of which will have treatment cycles of 28 days.
The subject must have confirmation of AML by 2022 WHO criteria, previously untreated and be ineligible for treatment with a standard cytarabine and anthracycline based induction regimen due to age and/or comorbidities.
≥ 75 years of age;
ECOG Performance Status of 2 or 3;
Cardiac history of cardiac heart failure (CHF) requiring treatment or left ventricular ejection fraction (LVEF) >45% and ≤ 55% or chronic stable angina.
Age <18 years old at screening.
Subject has received prior treatment with hypomethylating agent, FLT3 or BCL2 inhibitors.
Confirmed diagnosis of prior myelodysplastic syndrome (MDS) or a myeloproliferative neoplasm (MPN) or MDS/MPNs including CMML, aCML, JMML and others. This exclusion criterion will not be applicable to patients with FLT3 or NPM1 mutations (as per technical sensitivity threshold of local and/or central laboratory), who can be enrolled.
Genetic diagnosis of acute promyelocytic leukemia.