A Study Comparing Venetoclax and Azacitidine Plus Cusatuzumab to Venetoclax and Azacitidine in Newly Diagnosed AML Ineligible for Intensive Therapy

Inclusion Criteria

• •Men and women ≥18 years old
• •Must sign an informed consent form (ICF) indicating that he or she understands the purpose of, and procedures required for the study and is willing to participate in the study
• •Diagnosis of AML according to ICC 2022 (with the exclusion of MDS/AML with 10-19% blasts)
• •Previously untreated AML except may have received emergency leukapheresis, hydroxyurea before study entry to control hyperleukocytosis
• •Deemed unfit for intensive chemotherapy by meeting at least 1 of the following criteria:
• •1. Participant is ≥75 years of age with Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 OR
• •2. Participant is ≥18 to 74 years of age and has any of the following comorbidities:
• •1. ECOG performance status of 2 or 3
• •2. Cardiac status including any one of the following: congestive heart failure requiring treatment or ejection fraction ≤50% or chronic stable angina
• •3. Known history of diffusion capacity of lung for carbon monoxide (DLCO) ≤65% of forced expiratory volume in the first second (FEV1) ≤65%
• •4. Creatinine clearance (CrCl) ≥15 mL/min to \<45 mL/min
• •5. Hepatic disorder with total bilirubin \>1.5 to 3x the upper limit of normal (ULN)
• •6. Any other comorbidity that the investigators determine to be incompatible with conventional intensive chemotherapy
• •Adequate liver and renal function defined as:
• •1. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \<3xULN; for participants with leukemic infiltration of the liver (documented by biopsy or imaging), AST and ALT \<5xULN is permitted
• •2. Total bilirubin ≤1.5xULN, unless bilirubin rise is due to Gilbert's syndrome or of nonhepatic origin. Participants who are \<75 years of age may have a bilirubin up to 3xULN.
• •3. Estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 (by the Modification of Diet in Renal Disease \[MDRD\] formula). Participants who are \<75 years of age may have an eGFR ≥15 mL/min/1.73 m2.
• •Women of childbearing potential (WOCBP), defined as fertile women between menarche and post menopause unless permanently sterile, must have a negative highly sensitive serum β-human chorionic gonadotropin (β-hCG) or urine pregnancy test at screening
• •Must be willing to use contraception as consistent with institutional guidelines regarding the use of contraceptive methods for participants participating in clinical studies
• •1. WOCBP must agree to adhere to the following birth control measures while receiving study treatment continuing to 3 months after the last dose of study drug:
• •1. Must be practicing a highly effective method of birth control (failure rate of \<1% per year when used consistently and correctly) as determined by institutional standards
• •2. Must agree to not donate eggs (ova, oocytes) for the purposes of assisted reproduction
• •3. Must not be breastfeeding and not planning to become pregnant
• •2. Male participants who are sexually active with WOCBP, and male partners of study participants who are WOCBP, and who are not surgically or otherwise sterile must agree to adhere to the following birth control measures while receiving study treatment and for 3 months after the last dose of study drug:
• •1. Must agree to use a barrier method of birth control (e.g., either condom with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap \[diaphragm or cervical/vault caps\] with spermicidal foam, gel, film, cream, or suppository)
• •2. Must not donate sperm
• •3. Must no plan to father a child
• •Participants with HIV infection are eligible for the trial if the following criteria are met:
• •1. CD4+ T-cell count ≥200 cells/μL
• •2. No prior history of AIDS-defining opportunistic infection within the past 12 months
• •3. Receiving treatment with antiretroviral therapy
• •4. Undetectable viral load within 6 months of screening