A Study of Tagraxofusp in Combination With Venetoclax and Azacitidine in Adults With Untreated CD123+ Acute Myeloid Leukemia Who Cannot Undergo Intensive Chemotherapy
NCT Number: NCT06456463
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Acute Myeloid Leukemia
Interventions: DRUG: Tagraxofusp|DRUG: Venetoclax|DRUG: Azacitidine
Sponsor: Stemline Therapeutics, Inc.
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 76
Study Design: Allocation: RANDOMIZED|Intervention Model: SEQUENTIAL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-08-30
Completion Date: 2030-02-11
Locations: University of California, Los Angeles, Los Angeles, California, 90095, United States|University of Miami Sylvester Comprehensive Cancer Center, Miami, Florida, 33136, United States|AdventHealth Cancer Institute, Orlando, Florida, 32804, United States|Dana Farber Cancer Institute (DFCI), Boston, Massachusetts, 02114, United States|Massachusetts General Hospital, Boston, Massachusetts, 02114, United States|Washington University - Siteman Cancer Center, Saint Louis, Missouri, 63110, United States|John Theurer Cancer Center - Hackensack Meridian Health, Hackensack, New Jersey, 07601, United States|Rutgers Cancer Institute, New Brunswick, New Jersey, 08901, United States|Roswell Park Comprehensive Cancer Center, Buffalo, New York, 14203, United States|North Shore University Hospital, Manhasset, New York, 11030, United States|NYU Langone Health, New York, New York, 10016, United States|Columbia University Irving Medical Center, New York, New York, 10032, United States|Novant Health Presbyterian Medical Center, Charlotte, North Carolina, 28204, United States|Cleveland Clinic Foundation, Cleveland, Ohio, 44195, United States|Lifespan Cancer Institute, Providence, Rhode Island, 02903, United States|Baylor Scott & White Health, Dallas, Texas, 75246, United States|University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, United States|Hunstman Cancer Institute, Salt Lake City, Utah, 84132, United States

Summary:
This study will be divided into 2 parts (Part 1 and Part 2). Part 1 will evaluate 2 doses of tagraxofusp, 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. Both parts will be conducted in participants with previously untreated CD123+ AML who are ineligible for intensive chemotherapy.

Primary Outcome Measures: Part 2: Number of Participants Achieving a Best Overall Response (BOR) of Complete Remission (CR), Cycles 1-4 (up to 112 days; 28 days/cycle)
Secondary Outcome Measures: Parts 1 and 2: Number of Participants Achieving a BOR of CR, Cycles 1-6 (up to 168 days; 28 days/cycle)|Parts 1 and 2: Time to First CR, The time to first CR will be defined as the time from randomization (Cycle 1, Day 1) to the date of first documented CR., Cycles 1-6 (up to 168 days; 28 days/cycle)|Parts 1 and 2: Duration of Response, Cycles 1-6 (up to 168 days; 28 days/cycle)|Parts 1 and 2: Number of Participants Achieving a BOR of CR, CR with Incomplete Hematologic Recovery (CRi), or CR with Partial Hematologic Recovery (CRh), Cycles 1-4 (up to 112 days; 28 days/cycle)|Parts 1 and 2: Time to First Composite CR, The time to first composite CR will be defined as the time from randomization (Cycle 1, Day 1) to the date of first documented CR, CRi, or CRh., Cycles 1-4 (up to 112 days; 28 days/cycle)|Parts 1 and 2: Number of Participants Achieving a BOR of CR or CRi, Cycles 1-6 (up to 168 days; 28 days/cycle)|Parts 1 and 2: Time to first CR/CRi, The time to first CR/CRi will be defined as the time from randomization (Cycle 1, Day 1) to the date of first documented CR or CRi., Cycles 1-6 (up to 168 days; 28 days/cycle)|Parts 1 and 2: Event-free Survival (EFS), EFS will be defined as the time from the date of randomization (Cycle 1, Day 1) until the date of treatment failure, hematologic relapse after CR/CRi/CRh, or death from any cause, whichever occurs first., Up to approximately 6 years|Parts 1 and 2: CR with Minimal Residual Disease (MRD) Negative, Defined as the number of participants with a presence of marrow MRD of less than 0.01% at the time of CR., Cycles 1-6 (up to 168 days; 28 days/cycle)|Parts 1 and 2: Number of Participants Who Bridged to Stem Cell Transplant (SCT) Through Study Treatment, Up to approximately 6 years|Parts 1 and 2: Plasma Concentration of Free Tagraxofusp, Venetoclax, and Azacitidine, Predose, up to 8 hours post dose (Days 4, 5, 6, 7, 14; Cycles 1-6; 28 days/cycle)|Parts 1 and 2: Number of Participants With Serum Anti-drug Antibodies for Tagraxofusp, Venetoclax, and Azacitidine, Day 4 of each cycle (each cycle is 28 days) up to the end of study (approximately 6 years)|Parts 1 and 2: Exposure-response of Free Tagraxofusp When Administered in Combination with Venetoclax and Azacitidine, The exposure-response relationship will be assessed utilizing the CR rate/composite CR rate and the number of participants experiencing adverse events of interest. This model-based analysis will be conducted to compare the exposure and response of free tagraxofusp, venetoclax, and azacitidine with venetoclax and azacitidine. Results will be reported as percent probability, wherein changes in the percent probability would indicate corresponding changes in the response rates with changes in exposure., Up to approximately 6 years