Acute Myeloid Leukemia Clinical Trial
Study of ADI-PEG 20, Venetoclax and Azacitidine in Acute Myeloid Leukemia
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.
This is an open label, single arm, phase 1 trial with recommended phase 2 dose (RP2D) cohorts based on subject inclusion criteria.
Lead In: 6 patients will be enrolled to be treated with standard dose of azacitidine and venetoclax and the expected RP2D of ADI-PEG 20 (dose level 0). In case of DLT occurring in >1 patient in cycle 1, 6 additional patients will be accrued at dose level -1 of ADI-PEG 20 while keeping the doses of azacitidine and venetoclax unchanged (Dose level -1). Enrollment to cohort 1 and 2 will start after ≤1 patient out of 6 encounters DLT in cycle 1 at one of these dose levels. The 6 patients enrolled at that dose level will be counted for efficacy analysis in Cohort 1. Cohort 1: Relapsed or refractory AML: target response 25%. Historical expectation for venetoclax and azacitidine is 15%.
Cohort 2: Newly diagnosed high risk AML: Target response 55%. Historical expectation for venetoclax and azacitidine is 40%.
Treatment may be continued for a total of 24 cycles, each of 28 days.
Lead In and Cohort 1
Previously treated AML based on the revised 2017 European LeukemiaNet (ELN) criteria and having ≥10% blasts in bone marrow or peripheral blood
Age ≥18 years
Untreated AML per ELN criteria with high risk features
Age ≥ 65 years and ineligible for intensive chemotherapy because of older than 75 years, cardiac disease or prior anthracycline use or high probability of treatment-related mortality
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
Prior treatment for antecedent hematological disorders with hypomethylating agent (more than 2 cycles, those with exposure to <2 cycles will be allowed), venetoclax, or chemotherapy for antecedent hematologic disorders (treatment with other agents including hydroxyurea myelodysplastic syndrome myeloproliferative neoplasm is permitted)
Favorable risk AML per ELN 2017 criteria
Known active CNS involvement by leukemia
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