A Study of Tagraxofusp in Combination With Venetoclax and Azacitidine in Adults With Untreated CD123+ Acute Myeloid Leukemia Who Cannot Undergo Intensive Chemotherapy
- Conditions
- Acute Myeloid Leukemia
- Interventions
- Registration Number
- NCT06456463
- Lead Sponsor
- Stemline Therapeutics, Inc.
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 76
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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.
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Participant has any level of CD123 expression on blasts confirmed centrally by flow cytometry.
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Must be considered ineligible for intensive chemotherapy, defined by the following:
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≥75 years of age; or
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≥18 to 74 years of age with at least 1 of the following comorbidities:
- 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 comorbidity that the investigator judges to be incompatible with intensive chemotherapy must be reviewed and approved by the Sponsor.
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ECOG performance status:
- 0 to 2 for participants ≥75 years of age, or
- 0 to 3 for participants ≥18 to 74 years of age.
Key
- Participant has received prior therapy for AML.
- Willing and able to receive standard induction therapy.
- Treatment for an antecedent hematologic disease with a hypomethylating agent, venetoclax, tagraxofusp, purine analogue, cytarabine, intensive chemotherapy, chimeric antigen receptor-T therapy, or other experimental therapies.
- AML with central nervous system involvement.
Note: Other inclusion/exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 1 - Tagraxofusp (9 μg/kg/day) Tagraxofusp Participants will receive tagraxofusp in combination with venetoclax and azacitidine. Part 1 - Tagraxofusp (9 μg/kg/day) Venetoclax Participants will receive tagraxofusp in combination with venetoclax and azacitidine. Part 1 - Tagraxofusp (9 μg/kg/day) Azacitidine Participants will receive tagraxofusp in combination with venetoclax and azacitidine. Part 1 - Tagraxofusp (12 μg/kg/day) Tagraxofusp Participants will receive tagraxofusp in combination with venetoclax and azacitidine. Part 1 - Tagraxofusp (12 μg/kg/day) Venetoclax Participants will receive tagraxofusp in combination with venetoclax and azacitidine. Part 1 - Tagraxofusp (12 μg/kg/day) Azacitidine Participants will receive tagraxofusp in combination with venetoclax and azacitidine. Part 2 - Tagraxofusp (Selected Dose) and TP53 Wild Type Tagraxofusp Participants (TP53 wild type) will receive tagraxofusp in combination with venetoclax and azacitidine. Part 2 - Tagraxofusp (Selected Dose) and TP53 Wild Type Venetoclax Participants (TP53 wild type) will receive tagraxofusp in combination with venetoclax and azacitidine. Part 2 - Tagraxofusp (Selected Dose) and TP53 Wild Type Azacitidine Participants (TP53 wild type) will receive tagraxofusp in combination with venetoclax and azacitidine. Part 2 - Tagraxofusp (Selected Dose) and TP53 Mutated Tagraxofusp Participants (TP53 mutated) will receive tagraxofusp in combination with venetoclax and azacitidine. Part 2 - Tagraxofusp (Selected Dose) and TP53 Mutated Venetoclax Participants (TP53 mutated) will receive tagraxofusp in combination with venetoclax and azacitidine. Part 2 - Tagraxofusp (Selected Dose) and TP53 Mutated Azacitidine Participants (TP53 mutated) will receive tagraxofusp in combination with venetoclax and azacitidine.
- Primary Outcome Measures
Name Time Method Part 1: Determination of Part 2 Selected Dose of Tagraxofusp When Administered in Combination with Venetoclax and Azacitidine Cycles 1-4 (up to 112 days; 28 days/cycle) 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
Name Time Method 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 Cycles 1-6 (up to 168 days; 28 days/cycle) The time to first CR will be defined as the time from randomization (Cycle 1, Day 1) to the date of first documented CR.
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: 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: Time to First Composite CR Cycles 1-4 (up to 112 days; 28 days/cycle) 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.
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 Cycles 1-6 (up to 168 days; 28 days/cycle) 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.
Parts 1 and 2: Event-free Survival (EFS) Up to approximately 6 years 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.
Parts 1 and 2: CR with Minimal Residual Disease (MRD) Negative Cycles 1-6 (up to 168 days; 28 days/cycle) Defined as the number of participants with a presence of marrow MRD of less than 0.01% at the time of CR.
Parts 1 and 2: Exposure-response of Free Tagraxofusp When Administered in Combination with Venetoclax and Azacitidine Up to approximately 6 years 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.
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)
Trial Locations
- Locations (30)
University of California, Los Angeles
🇺🇸Los Angeles, California, United States
University of Miami Sylvester Comprehensive Cancer Center
🇺🇸Miami, Florida, United States
AdventHealth Cancer Institute
🇺🇸Orlando, Florida, United States
Dana Farber Cancer Institute (DFCI)
🇺🇸Boston, Massachusetts, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Henry Ford Health
🇺🇸Detroit, Michigan, United States
Washington University - Siteman Cancer Center
🇺🇸Saint Louis, Missouri, United States
John Theurer Cancer Center - Hackensack Meridian Health
🇺🇸Hackensack, New Jersey, United States
Rutgers Cancer Institute
🇺🇸New Brunswick, New Jersey, United States
Roswell Park Comprehensive Cancer Center
🇺🇸Buffalo, New York, United States
North Shore University Hospital
🇺🇸Manhasset, New York, United States
NYU Langone Health
🇺🇸New York, New York, United States
Columbia University Irving Medical Center
🇺🇸New York, New York, United States
Novant Health Presbyterian Medical Center
🇺🇸Charlotte, North Carolina, United States
Novant Health Derrick L Davis Cancer Center
🇺🇸Winston-Salem, North Carolina, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Sarah Cannon, the Cancer Institute of HCA Healthcare
🇺🇸Nashville, Tennessee, United States
Tennessee Oncology
🇺🇸Nashville, Tennessee, United States
Baylor Scott & White Health
🇺🇸Dallas, Texas, United States
University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Huntsman Cancer Institute
🇺🇸Salt Lake City, Utah, United States
Concord Repatriation General Hospital
🇦🇺Concord, New South Wales, Australia
Townsville Hospital
🇦🇺Townsville, Queensland, Australia
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
Box Hill Hospital
🇦🇺Box Hill, Victoria, Australia
Monash Medical Centre
🇦🇺Clayton, Victoria, Australia
St. Vincents Hospital
🇦🇺Fitzroy, Victoria, Australia
Austin Hospital
🇦🇺Heidelberg, Victoria, Australia
Royal Perth Hospital
🇦🇺Perth, Western Australia, Australia