Phase IA/B Combination Study of ADI-PEG 20, Venetoclax and Azacitidine in Patients with Acute Myeloid Leukemia (AML)
Pegylated arginine deiminase (ADI-PEG 20) will be combined with venetoclax and azacitidine for treatment of subjects with previously treated or untreated with high risk factor acute myeloid leukemia (AML). Venetoclax and azacitidine are front-line therapy for such patients, and ADI-PEG 20 will be added to this regimen in a phase IA/B study.
• Cohort 1: Previously treated (relapsed/recurrent) or refractory AML based on the 2022 revision to the World Health Organization (WHO) criteria (Arber 2022)
• Cohort 2: Untreated AML per 2022 WHO (Arber 2022) criteria with high-risk features and not a candidate for intensive chemotherapy because of age 60 years or older, age-related comorbidities, cardiac disease, prior anthracycline use, high probability of treatment-related mortality, or otherwise would not benefit from intensive chemotherapy treatment.
• Age ≥ 18 years
• Life expectancy reasonably adequate for evaluating the treatment
• White blood cell (WBC) count of 10 × 109/L or less. (Use of hydroxyurea to control WBC is allowed till 48 hours prior to protocol treatment)
• Adequate renal function: Creatinine ≤ 1.5 x upper limit of normal (ULN) or creatinine clearance \> 40 mL/minute (measured or calculated according to the Cockcroft-Gault formula)
• Adequate liver function
‣ Total bilirubin ≤ 1.5 x ULN
⁃ ALT and AST both ≤ 2.5 x institutional ULN or ≤ 5 times the ULN for patients with leukemic involvement of liver