Venetoclax Plus Azacitidine Versus Standard Intensive Chemotherapy for Patients With Newly Diagnosed Acute Myeloid Leukemia (AML) and NPM1 Mutations Eligible for Intensive Treatment
This phase II clinical trial evaluates the efficacy and tolerability of the non-intensive treatment with venetoclax and the hypomethylating agent azacitidine as compared to the standard of care chemotherapy plus gemtuzumab ozogamicin in newly diagnosed NPM1 mutated AML patients fit for intensive chemotherapy.
• A signed informed consent
• Newly diagnosed CD33-positive AML with NPM1 mutation according to WHO criteria
• Age 18-70 years
• Fit for intensive chemotherapy, defined by
‣ ECOG performance status of 0-2
⁃ Adequate hepatic function: ALAT/ASAT/Bilirubin ≤ 2.5 x ULN unless considered due to leukemic organ involvement Note: Subjects with Gilbert's Syndrome may have a bilirubin \> 2.5 × ULN per discussion between the investigator and Coordinating investigator.
⁃ Adequate renal function assessed by serum creatinine ≤ 1.5x ULN OR creatinine clearance (by Cockcroft Gault formula) ≥ 50 mL/min
• WBC \< 25 x 109/L (\<25,000/µL), prior hydroxyurea is permitted to meet this criterion
• Ability to understand and the willingness to sign a written informed consent.
• Male subjects must agree to refrain from unprotected sex and sperm donation from time point of signing the informed consent until 7 months after the last dose of study drug.
• Women of childbearing potential must have a negative serum or urine pregnancy test performed within 72 hours before first dose of study drug.