A Study of Tagraxofusp in Combination With Venetoclax and Azacitidine in Adults With Untreated CD123+ Acute Myeloid Leukemia Who Cannot Undergo Intensive Chemotherapy
A Phase II Multicenter Open-label Trial of Tagraxofusp (Tag) in Combination With Venetoclax and Azacitidine (Ven/Aza) in Adults With Previously Untreated CD123+ Acute Myeloid Leukemia (AML) Who Are Ineligible for Intensive Chemotherapy
Stemline Therapeutics, Inc.
83 participants
Jan 14, 2025
INTERVENTIONAL
Conditions
Summary
This study will be divided into 2 parts (Part 1 and Part 2). Part 1 will evaluate 2 doses of tagraxofusp (9 and 12 micrograms/kilogram/day \[μg/kg/day\]), used in combination with venetoclax and azacitidine, to determine the dose for Part 2. This determined dose, in combination with venetoclax and azacitidine, will then be further evaluated in Part 2 in 2 cohorts (TP53 mutated and TP53 wild type). Both parts will be conducted in participants with previously untreated CD123+ AML who are ineligible for intensive chemotherapy.
Eligibility
Inclusion Criteria13
- Previously untreated with histological confirmation of AML by World Health Organization 2022 criteria and are ineligible for treatment with a standard cytarabine and anthracycline induction regimen due to age, or comorbidity.
- Participant has any level of CD123 expression on blasts.
- Participants must be considered ineligible for intensive chemotherapy, defined by the following:
- ≥75 years of age; or
- ≥18 to 74 years of age with at least 1 of the following:
- Eastern Cooperative Oncology Group (ECOG) performance status of 2 or 3.
- Diffusing capacity of the lung for carbon monoxide of ≤65% or forced expiratory volume in 1 second ≤65%.
- Baseline creatinine clearance ≥30 to \<45 milliliters/minute calculated by the Cockcroft Gault formula or measured by 24-hour urine collection.
- Hepatic disorder with total bilirubin \>1.5 x upper limit of normal.
- Any other condition for which the physician judges the participant to be unsuitable for intensive chemotherapy.
- ECOG performance status:
- to 2 for participants ≥75 years of age, or
- to 3 for participants ≥18 to 74 years of age.
Exclusion Criteria4
- Participant has received prior therapy for AML.
- Participant is willing and able to receive standard induction therapy.
- Participant has received treatment for an antecedent hematologic disease with a hypomethylating agent, venetoclax, tagraxofusp, purine analogue, cytarabine, intensive chemotherapy, SCT, chimeric antigen receptor-T therapy, or other experimental therapies.
- Participant has AML with central nervous system involvement.
Interventions
Tagraxofusp will be administered by intravenous infusion for 3 consecutive days during each 28-day cycle.
Venetoclax will be administered as an oral tablet (400 milligrams \[mg\]) daily, with ramp up in Cycle 1, and should be continued at target dose (400 mg) for the remainder of Cycle 1 and subsequent cycles of 28 days each.
Azacitidine will be administered subcutaneously or by intravenous infusion (75 milligrams/square meter) over 7 days of each 28-day cycle, per institutional guidelines/physician choice.
Locations(32)
View Full Details on ClinicalTrials.gov
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NCT06456463