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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: Azacitidine; Drug: Tagraxofusp; Drug: Venetoclax

• Study Type: Interventional
• Enrollment (Estimated): 83
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Stemline Trials; Phone Number: 1-877-332-7961; Email: clinicaltrials@menarinistemline.com

Study Locations

• Australia
  • New South Wales
    • Concord, New South Wales, Australia, 2139
      • Recruiting
      • Concord Repatriation General Hospital
      • Principal Investigator: Robin Gasiorowski, MBBS
  • Queensland
    • Douglas, Queensland, Australia, 4814
      • Recruiting
      • Townsville Hospital
      • Principal Investigator: Rachael Boles, MD
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Recruiting
      • Royal Adelaide Hospital
      • Principal Investigator: Devendra Hiwase, MBBS
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Recruiting
      • Box Hill Hospital
      • Principal Investigator: Stephen Ting, MBBS
    • Clayton, Victoria, Australia, 3168
      • Recruiting
      • Monash Medical Centre
      • Principal Investigator: Ashvind Prabahran, MD
    • Fitzroy, Victoria, Australia, 3065
      • Recruiting
      • St. Vincents Hospital
      • Principal Investigator: Shuh Ying Tan, MBBS
    • Heidelberg, Victoria, Australia, 3084
      • Recruiting
      • Austin Hospital
      • Principal Investigator: Chun Yew Fong, MBBS, PhD
  • Western Australia
    • Perth, Western Australia, Australia, 6000
      • Recruiting
      • Royal Perth Hospital
      • Principal Investigator: Hun Chuah, MBBS, PhD
• United States
  • California
    • Los Angeles, California, United States, 90095
      • Recruiting
      • University of California, Los Angeles
      • Principal Investigator: Gary Schiller, MD
    • Stanford, California, United States, 94305
      • Recruiting
      • Stanford Health Care
      • Principal Investigator: Gabriel Mannis, MD
  • Florida
    • Miami, Florida, United States, 33136
      • Recruiting
      • University of Miami
      • Principal Investigator: Namrata Chandhok, MD
    • Orlando, Florida, United States, 32804
      • Recruiting
      • AdventHealth Cancer Institute
      • Principal Investigator: Shahram Mori, MD, PhD
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • University of Chicago
      • Principal Investigator: Anand Patel, MD
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
      • Principal Investigator: Amir Fathi, MD
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Beth Israel Deaconess Medical Center
      • Principal Investigator: Malgorzata McMasters, MD
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Dana Farber Cancer Institute (DFCI)
      • Principal Investigator: Andrew A Lane, MD, PhD
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Recruiting
      • Henry Ford Health System Brigitte Harris Cancer Pavillion
      • Principal Investigator: Christopher A Willner II, DO
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University - Siteman Cancer Center
      • Principal Investigator: Geoffrey L Uy, MD
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Recruiting
      • John Theurer Cancer Center - Hackensack Meridian Health
      • Principal Investigator: James K McCloskey, MD
    • New Brunswick, New Jersey, United States, 08901
      • Recruiting
      • Rutgers Cancer Institute
      • Principal Investigator: Neil D Palmisiano, MD, MS
  • New York
    • Buffalo, New York, United States, 14203
      • Recruiting
      • Roswell Park Cancer Institute
      • Principal Investigator: Eunice S Wang, MD
    • Manhasset, New York, United States, 11030
      • Recruiting
      • North Shore University Hospital
      • Principal Investigator: David Chitty, MD
    • New York, New York, United States, 10016
      • Recruiting
      • NYU Langone Health
      • Principal Investigator: Jun H Choi, MD
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Irving Medical Center
      • Principal Investigator: Sunil Iyer, MD
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Recruiting
      • Novant Health Presbyterian Medical Center
      • Principal Investigator: Abhishek Chilkulwar, MD
    • Winston-Salem, North Carolina, United States, 27103
      • Recruiting
      • Novant Health Derrick L Davis Cancer Center
      • Principal Investigator: Abhishek Chilkulwar, MD
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic Foundation
      • Principal Investigator: Akriti Jain, MD
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Recruiting
      • Sydney Kimmel (Thomas Jefferson University)
      • Principal Investigator: Gina Keiffer, MD
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Tennessee Oncology
      • Principal Investigator: Jonathan Abbas, MD
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Sarah Cannon, the Cancer Institute of HCA Healthcare
      • Principal Investigator: Stephen A Strickland, MD
  • Texas
    • Dallas, Texas, United States, 75246
      • Recruiting
      • Baylor Scott & White Health
      • Principal Investigator: Bradley W Christensen, MD
    • Houston, Texas, United States, 77030
      • Recruiting
      • University of Texas MD Anderson Cancer Center
      • Principal Investigator: Naval G Daver, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 - Tagraxofusp (9 μg/kg/day); Participants will receive tagraxofusp in combination with venetoclax and azacitidine.	Drug: Azacitidine; 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.; Other Names: Vidaza; Aza; Drug: Tagraxofusp; Tagraxofusp will be administered by intravenous infusion for 3 consecutive days during each 28-day cycle.; Other Names: Elzonris; Tag; Drug: Venetoclax; 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.; Other Names: Venclexta; Ven
Experimental: Part 1 - Tagraxofusp (12 μg/kg/day); Participants will receive tagraxofusp in combination with venetoclax and azacitidine.	Drug: Azacitidine; 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.; Other Names: Vidaza; Aza; Drug: Tagraxofusp; Tagraxofusp will be administered by intravenous infusion for 3 consecutive days during each 28-day cycle.; Other Names: Elzonris; Tag; Drug: Venetoclax; 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.; Other Names: Venclexta; Ven
Experimental: Part 2 - Tagraxofusp (Selected Dose) and TP53 Wild Type; Participants (TP53 wild type) will receive tagraxofusp in combination with venetoclax and azacitidine.	Drug: Azacitidine; 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.; Other Names: Vidaza; Aza; Drug: Tagraxofusp; Tagraxofusp will be administered by intravenous infusion for 3 consecutive days during each 28-day cycle.; Other Names: Elzonris; Tag; Drug: Venetoclax; 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.; Other Names: Venclexta; Ven
Experimental: Part 2 - Tagraxofusp (Selected Dose) and TP53 Mutated; Participants (TP53 mutated) will receive tagraxofusp in combination with venetoclax and azacitidine.	Drug: Azacitidine; 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.; Other Names: Vidaza; Aza; Drug: Tagraxofusp; Tagraxofusp will be administered by intravenous infusion for 3 consecutive days during each 28-day cycle.; Other Names: Elzonris; Tag; Drug: Venetoclax; 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.; Other Names: Venclexta; Ven

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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)
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)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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: 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
Parts 1 and 2: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)		Up to approximately 6 years
Parts 1 and 2: Overall Survival		Up to approximately 6 years
Parts 1 and 2: Maximum Plasma Concentration (Cmax) of Tagraxofusp and Venetoclax		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		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		Predose, up to 8 hours post dose (Days 4, 5, 6, 7, 14; Cycles 1-4; 28 days/cycle)
Part 1: Plasma Concentration of Free Tagraxofusp, Venetoclax, and Azacitidine		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		Predose, up to 8 hours post dose (Days 4, 5, 6, 7, 14; Cycles 1-4; 28 days/cycle)

Collaborators and Investigators

• Sponsor: Stemline Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 14, 2025
• Primary Completion (Estimated): February 9, 2028
• Study Completion (Estimated): February 11, 2030

Study Registration Dates

• First Submitted: May 31, 2024
• First Submitted That Met QC Criteria: June 7, 2024
• First Posted (Actual): June 13, 2024

Study Record Updates

• Last Update Posted (Actual): March 9, 2026
• Last Update Submitted That Met QC Criteria: March 5, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Venetoclax; Azacitidine; CD123+; Tagraxofusp
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Leukemia; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Technology, Industry, and Agriculture; Aza Compounds; Nucleosides; Ribonucleosides; Industry; Product Packaging; Azacitidine; venetoclax; tagraxofusp; Product Labeling
• Other Study ID Numbers: STML-401-0423; U1111-1290-9087 (Other Identifier: UTN); 2024-514660-48 (Other Identifier: EU CT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No