Cancerify Logo
Log inSign up
Back to clinical trials
RecruitingInterventionalPhase 2

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

NCT ID: NCT06456463Sponsor: Stemline Therapeutics, Inc.Last updated: 2026-03-09

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.

Arms & interventions

  • DrugTagraxofusp

    Tagraxofusp will be administered by intravenous infusion for 3 consecutive days during each 28-day cycle.

  • DrugVenetoclax

    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.

  • DrugAzacitidine

    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.

Outcome measures

Primary

  • Part 1: Determination of Part 2 Selected Dose of Tagraxofusp When Administered in Combination with Venetoclax and Azacitidine

    Time frame: 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)

    Time frame: Cycles 1-4 (up to 112 days; 28 days/cycle)

Secondary

  • Parts 1 and 2: Number of Participants Achieving a BOR of CR

    Time frame: Cycles 1-6 (up to 168 days; 28 days/cycle)

  • Parts 1 and 2: Time to First CR

    Time frame: Cycles 1-6 (up to 168 days; 28 days/cycle)

  • Parts 1 and 2: Duration of Response

    Time frame: 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)

    Time frame: Cycles 1-4 (up to 112 days; 28 days/cycle)

  • Parts 1 and 2: Time to First Composite CR

    Time frame: Cycles 1-4 (up to 112 days; 28 days/cycle)

  • Parts 1 and 2: Number of Participants Achieving a BOR of CR or CRi

    Time frame: Cycles 1-6 (up to 168 days; 28 days/cycle)

  • Parts 1 and 2: Time to first CR/CRi

    Time frame: Cycles 1-6 (up to 168 days; 28 days/cycle)

  • Parts 1 and 2: Event-free Survival (EFS)

    Time frame: Up to approximately 6 years

  • Parts 1 and 2: CR with Minimal Residual Disease (MRD) Negative

    Time frame: 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

    Time frame: Up to approximately 6 years

  • Part 1: Plasma Concentration of Free Tagraxofusp, Venetoclax, and Azacitidine

    Time frame: Predose, up to 8 hours post dose (Days 4, 5, 6, 7, 14; Cycles 1-4; 28 days/cycle)

  • Part 2: Plasma Concentration of Free Tagraxofusp and Venetoclax

    Time frame: Predose, up to 8 hours post dose (Days 4, 5, 6, 7, 14; Cycles 1-4; 28 days/cycle)

  • Parts 1 and 2: Number of Participants With Serum Anti-drug Antibodies for Tagraxofusp, Venetoclax, and Azacitidine

    Time frame: 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

    Time frame: Up to approximately 6 years

  • Parts 1 and 2: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

    Time frame: Up to approximately 6 years

  • Parts 1 and 2: Overall Survival

    Time frame: Up to approximately 6 years

  • Parts 1 and 2: Maximum Plasma Concentration (Cmax) of Tagraxofusp and Venetoclax

    Time frame: Predose, up to 8 hours post dose (Days 4, 5, 6, 7, 14; Cycles 1-4; 28 days/cycle)

  • Parts 1 and 2: Time to Reach Cmax (Tmax) of Tagraxofusp and Venetoclax

    Time frame: Predose, up to 8 hours post dose (Days 4, 5, 6, 7, 14; Cycles 1-4; 28 days/cycle)

  • Parts 1 and 2: Area Under the Concentration-time Curve (AUC) of Tagraxofusp and Venetoclax

    Time frame: Predose, up to 8 hours post dose (Days 4, 5, 6, 7, 14; Cycles 1-4; 28 days/cycle)

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
Key Inclusion Criteria: * 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: * 0 to 2 for participants ≥75 years of age, or * 0 to 3 for participants ≥18 to 74 years of age. Key Exclusion Criteria: * 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. Note: Other inclusion/exclusion criteria may apply.

Study locations (24)

University of California, Los Angeles

Los Angeles, California, 90095

Recruiting
Gary Schiller, MD · Principal Investigator

Stanford Health Care

Stanford, California, 94305

Recruiting
Gabriel Mannis, MD · Principal Investigator

University of Miami

Miami, Florida, 33136

Recruiting
Namrata Chandhok, MD · Principal Investigator

AdventHealth Cancer Institute

Orlando, Florida, 32804

Recruiting
Shahram Mori, MD, PhD · Principal Investigator

University of Chicago

Chicago, Illinois, 60637

Recruiting
Anand Patel, MD · Principal Investigator

Dana Farber Cancer Institute (DFCI)

Boston, Massachusetts, 02114

Recruiting
Andrew A Lane, MD, PhD · Principal Investigator

Massachusetts General Hospital

Boston, Massachusetts, 02114

Recruiting
Amir Fathi, MD · Principal Investigator

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215

Recruiting
Malgorzata McMasters, MD · Principal Investigator

Henry Ford Health System Brigitte Harris Cancer Pavillion

Detroit, Michigan, 48202

Recruiting
Christopher A Willner II, DO · Principal Investigator

Washington University - Siteman Cancer Center

St Louis, Missouri, 63110

Recruiting
Geoffrey L Uy, MD · Principal Investigator

John Theurer Cancer Center - Hackensack Meridian Health

Hackensack, New Jersey, 07601

Recruiting
James K McCloskey, MD · Principal Investigator

Rutgers Cancer Institute

New Brunswick, New Jersey, 08901

Recruiting
Neil D Palmisiano, MD, MS · Principal Investigator

Roswell Park Cancer Institute

Buffalo, New York, 14203

Recruiting
Eunice S Wang, MD · Principal Investigator

North Shore University Hospital

Manhasset, New York, 11030

Recruiting
David Chitty, MD · Principal Investigator

NYU Langone Health

New York, New York, 10016

Recruiting
Jun H Choi, MD · Principal Investigator

Columbia University Irving Medical Center

New York, New York, 10032

Recruiting
Sunil Iyer, MD · Principal Investigator

Novant Health Presbyterian Medical Center

Charlotte, North Carolina, 28204

Recruiting
Abhishek Chilkulwar, MD · Principal Investigator

Novant Health Derrick L Davis Cancer Center

Winston-Salem, North Carolina, 27103

Recruiting
Abhishek Chilkulwar, MD · Principal Investigator

Cleveland Clinic Foundation

Cleveland, Ohio, 44195

Recruiting
Akriti Jain, MD · Principal Investigator

Sydney Kimmel (Thomas Jefferson University)

Philadelphia, Pennsylvania, 19107

Recruiting
Gina Keiffer, MD · Principal Investigator

Sarah Cannon, the Cancer Institute of HCA Healthcare

Nashville, Tennessee, 37203

Recruiting
Stephen A Strickland, MD · Principal Investigator

Tennessee Oncology

Nashville, Tennessee, 37203

Recruiting
Jonathan Abbas, MD · Principal Investigator

Baylor Scott & White Health

Dallas, Texas, 75246

Recruiting
Bradley W Christensen, MD · Principal Investigator

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030

Recruiting
Naval G Daver, MD · Principal Investigator