A Study of Tagraxofusp in Combination With Venetoclax and Azacitidine in Adults With Untreated CD123+ Acute Myeloid Leukemia Who Cannot Undergo Intensive Chemotherapy

NCT06456463 | Recruiting Phase 2 FDA Drug

• 3 other identifiers: STML-401-0423U1111-1290-90872024-514660-48
• Study Type: interventional
• Target: 83
• Locations: 2 countries
• Sites: 32

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.

Conditions

Acute Myeloid Leukemia

Keywords

CD123+; Tagraxofusp; Venetoclax; Azacitidine

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (19)

• 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)

• 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

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

Study Arms (4)

Part 1 - Tagraxofusp (9 μg/kg/day)

EXPERIMENTAL

Participants will receive tagraxofusp in combination with venetoclax and azacitidine.

Drug: Tagraxofusp; Drug: Venetoclax; Drug: Azacitidine

Part 1 - Tagraxofusp (12 μg/kg/day)

EXPERIMENTAL

Participants will receive tagraxofusp in combination with venetoclax and azacitidine.

Drug: Tagraxofusp; Drug: Venetoclax; Drug: Azacitidine

Part 2 - Tagraxofusp (Selected Dose) and TP53 Wild Type

EXPERIMENTAL

Participants (TP53 wild type) will receive tagraxofusp in combination with venetoclax and azacitidine.

Drug: Tagraxofusp; Drug: Venetoclax; Drug: Azacitidine

Part 2 - Tagraxofusp (Selected Dose) and TP53 Mutated

EXPERIMENTAL

Participants (TP53 mutated) will receive tagraxofusp in combination with venetoclax and azacitidine.

Drug: Tagraxofusp; Drug: Venetoclax; Drug: Azacitidine

Interventions

Tagraxofusp DRUG

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

Also known as: Tag, Elzonris

Part 1 - Tagraxofusp (12 μg/kg/day); Part 1 - Tagraxofusp (9 μg/kg/day); Part 2 - Tagraxofusp (Selected Dose) and TP53 Mutated; Part 2 - Tagraxofusp (Selected Dose) and TP53 Wild Type

Venetoclax DRUG

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.

Also known as: Ven, Venclexta

Part 1 - Tagraxofusp (12 μg/kg/day); Part 1 - Tagraxofusp (9 μg/kg/day); Part 2 - Tagraxofusp (Selected Dose) and TP53 Mutated; Part 2 - Tagraxofusp (Selected Dose) and TP53 Wild Type

Azacitidine DRUG

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.

Also known as: Aza, Vidaza

Part 1 - Tagraxofusp (12 μg/kg/day); Part 1 - Tagraxofusp (9 μg/kg/day); Part 2 - Tagraxofusp (Selected Dose) and TP53 Mutated; Part 2 - Tagraxofusp (Selected Dose) and TP53 Wild Type

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Stemline Therapeutics, Inc.: lead

Study Sites (32)

University of California, Los Angeles

Los Angeles, California, 90095, United States

RECRUITING

Stanford Health Care

Stanford, California, 94305, United States

RECRUITING

University of Miami

Miami, Florida, 33136, United States

RECRUITING

AdventHealth Cancer Institute

Orlando, Florida, 32804, United States

RECRUITING

University of Chicago

Chicago, Illinois, 60637, United States

RECRUITING

Dana Farber Cancer Institute (DFCI)

Boston, Massachusetts, 02114, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

RECRUITING

Henry Ford Health System Brigitte Harris Cancer Pavillion

Detroit, Michigan, 48202, United States

RECRUITING

Washington University - Siteman Cancer Center

St Louis, Missouri, 63110, United States

RECRUITING

John Theurer Cancer Center - Hackensack Meridian Health

Hackensack, New Jersey, 07601, United States

RECRUITING

Rutgers Cancer Institute

New Brunswick, New Jersey, 08901, United States

RECRUITING

Roswell Park Cancer Institute

Buffalo, New York, 14203, United States

RECRUITING

North Shore University Hospital

Manhasset, New York, 11030, United States

RECRUITING

NYU Langone Health

New York, New York, 10016, United States

RECRUITING

Columbia University Irving Medical Center

New York, New York, 10032, United States

RECRUITING

Novant Health Presbyterian Medical Center

Charlotte, North Carolina, 28204, United States

RECRUITING

Novant Health Derrick L Davis Cancer Center

Winston-Salem, North Carolina, 27103, United States

RECRUITING

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

RECRUITING

Sydney Kimmel (Thomas Jefferson University)

Philadelphia, Pennsylvania, 19107, United States

RECRUITING

Sarah Cannon, the Cancer Institute of HCA Healthcare

Nashville, Tennessee, 37203, United States

RECRUITING

Tennessee Oncology

Nashville, Tennessee, 37203, United States

RECRUITING

Baylor Scott & White Health

Dallas, Texas, 75246, United States

RECRUITING

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Concord Repatriation General Hospital

Concord, New South Wales, 2139, Australia

RECRUITING

Townsville Hospital

Douglas, Queensland, 4814, Australia

RECRUITING

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

RECRUITING

Box Hill Hospital

Box Hill, Victoria, 3128, Australia

RECRUITING

Monash Medical Centre

Clayton, Victoria, 3168, Australia

RECRUITING

St. Vincents Hospital

Fitzroy, Victoria, 3065, Australia

RECRUITING

Austin Hospital

Heidelberg, Victoria, 3084, Australia

RECRUITING

Royal Perth Hospital

Perth, Western Australia, 6000, Australia

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

tagraxofusp; Product Labeling; venetoclax; Azacitidine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Product Packaging; Industry; Technology, Industry, and Agriculture; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Central Study Contacts

Stemline Trials

CONTACT

1-877-332-7961; clinicaltrials@menarinistemline.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part 1 (randomized) will evaluate 2 dose levels of tagraxofusp in parallel. The decision to proceed to Part 2 (non-randomized) will be based upon review of cumulative data from Part 1.

Study Record Dates

• First Submitted: May 31, 2024
• First Posted: June 13, 2024
• Study Start: January 14, 2025
• Primary Completion (Estimated): February 9, 2028
• Study Completion (Estimated): February 11, 2030
• Last Updated: March 9, 2026

Record last verified: 2026-03

Locations

US (24); AU (8)