A Phase 1b/2 Open-Label Study of APVO436 in Combination With Venetoclax and Azacitidine in Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)
Summary
A multi-center, open-label, dose-finding study of five dose levels of APVO436 in combination with venetoclax and azacitidine (ven/aza) in adult patients with newly diagnosed, CD123+ AML.
Detailed description
Phase 1b consists of 28-day cycles of treatment in five sequential cohorts. In Cycle 1 (C1) only, to reduce the risk of CRS, each cohort will receive 4 priming doses of APVO436 respectively. APVO436 will be given in combination with venetoclax and azacitidine. For C1D15 and all doses in each subsequent cycle, cohorts will receive APVO436 at the determined cohort dose level. APVO436 dosing will be administered by a 4-hour intravenous (IV) infusion.
Arms & interventions
- DrugAPVO436
Infusion drug administered as a 4 hour infusion.
- DrugVenetoclax
Oral tablet given on days 1 through 22, of a 28 day cycle.
- DrugAzacitidine
Intravenous infusion given on days 1-8 of a 28 day cycle
Outcome measures
Primary
To assess the safety, tolerability, and maximum tolerated dose (MTD) of increasing doses of APVO436 in combination with venetoclax/azacitidine in patients with newly diagnosed AML
Incidence and severity of treatment emergent adverse events (TEAEs), including ≥Grade 3 adverse events (AEs), serious AEs (SAEs), and AEs of special interest (AESIs: ≥Grade 2 infusion related reaction (IRR), ≥Grade 2 cardiac toxicity, and ≥Grade 2 neurotoxicity as complication of cytokine release syndrome \[CRS\]).
Time frame: Through the end study completion average of 1 year.
Secondary
Determine the efficacy of increasing doses of APVO436 in combination with venetoclax and azacitidine in patients with newly diagnosed AML
Time frame: Through the end study completion average of 1 year.
Eligibility criteria
Study locations (7)
Colorado Blood Cancer Institute
Denver, Colorado, 80218
University of Miami
Miami, Florida, 33124
University of Kansas
Fairway, Kansas, 66205
Gabrail Cancer Center
Canton, Ohio, 44718
Oncology Hematology Care
Cincinnati, Ohio, 45226
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
MD Anderson Cancer Center
Houston, Texas, 77030