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NCT Number: NCT06456463

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

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Key information

Conditions

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

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Concord Repatriation General Hospital, Concord, New South Wales, Australia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Tagraxofusp

Drug

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

Other names: Tag, Elzonris

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.

Other names: Ven, Venclexta

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.

Other names: Aza, Vidaza

Primary outcomes

  1. 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)

  2. 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 outcomes

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

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

  2. Parts 1 and 2: Time to First CR

    Time frame: 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.

  3. Parts 1 and 2: Duration of Response

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

  4. 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)

  5. Parts 1 and 2: Time to First Composite CR

    Time frame: 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.

  6. 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)

  7. Parts 1 and 2: Time to first CR/CRi

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 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.

  10. Parts 1 and 2: Number of Participants Who Bridged to Stem Cell Transplant (SCT) Through Study Treatment

    Time frame: Up to approximately 6 years

  11. 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)

  12. 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)

  13. 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)

  14. Parts 1 and 2: Exposure-response of Free Tagraxofusp When Administered in Combination with Venetoclax and Azacitidine

    Time frame: 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.

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

    Time frame: Up to approximately 6 years

  16. Parts 1 and 2: Overall Survival

    Time frame: Up to approximately 6 years

  17. 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)

  18. 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)

  19. 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)

Study contacts

Contact information is provided by the study sponsor or research team.

Stemline Trials

CONTACT

[email protected]

1-877-332-7961

Sponsors and collaborators

Lead sponsor

Stemline Therapeutics, Inc.

Industry

Registry information

Official study title

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

Acronym: TRILLIUM

Important dates

Study start
2025
Primary completion
2028
Study completion
2030
First posted
Jun 13, 2024
Registry last updated
Mar 9, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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