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

Purpose

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.

Condition

  • Acute Myeloid Leukemia

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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 confirmed centrally by flow cytometry. - 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 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. - ECOG performance status: - 0 to 2 for participants ≥75 years of age, or - 0 to 3 for participants ≥18 to 74 years of age.

Exclusion Criteria

  • 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

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Sequential Assignment
Intervention Model Description
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.
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Part 1 - Tagraxofusp (9 μg/kg/day) 		Participants will receive tagraxofusp in combination with venetoclax and azacitidine.
  • Drug: Tagraxofusp
    Tagraxofusp will be administered by intravenous infusion for 3 consecutive days during each 28-day cycle.
    Other names:
    • Tag
    • Elzonris
  • Drug: Venetoclax
    Venetoclax will be administered as an oral tablet (400 milligrams) daily of each 28-day cycle.
    Other names:
    • Ven
    • Venclexta
  • 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:
    • Aza
    • Vidaza
Experimental
Part 1 - Tagraxofusp (12 μg/kg/day) 		Participants will receive tagraxofusp in combination with venetoclax and azacitidine.
  • Drug: Tagraxofusp
    Tagraxofusp will be administered by intravenous infusion for 3 consecutive days during each 28-day cycle.
    Other names:
    • Tag
    • Elzonris
  • Drug: Venetoclax
    Venetoclax will be administered as an oral tablet (400 milligrams) daily of each 28-day cycle.
    Other names:
    • Ven
    • Venclexta
  • 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:
    • Aza
    • Vidaza
Experimental
Part 2 - Tagraxofusp (Selected Dose) and TP53 Wild Type 		Participants (TP53 wild type) will receive tagraxofusp in combination with venetoclax and azacitidine.
  • Drug: Tagraxofusp
    Tagraxofusp will be administered by intravenous infusion for 3 consecutive days during each 28-day cycle.
    Other names:
    • Tag
    • Elzonris
  • Drug: Venetoclax
    Venetoclax will be administered as an oral tablet (400 milligrams) daily of each 28-day cycle.
    Other names:
    • Ven
    • Venclexta
  • 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:
    • Aza
    • Vidaza
Experimental
Part 2 - Tagraxofusp (Selected Dose) and TP53 Mutated 		Participants (TP53 mutated) will receive tagraxofusp in combination with venetoclax and azacitidine.
  • Drug: Tagraxofusp
    Tagraxofusp will be administered by intravenous infusion for 3 consecutive days during each 28-day cycle.
    Other names:
    • Tag
    • Elzonris
  • Drug: Venetoclax
    Venetoclax will be administered as an oral tablet (400 milligrams) daily of each 28-day cycle.
    Other names:
    • Ven
    • Venclexta
  • 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:
    • Aza
    • Vidaza

Recruiting Locations

Massachusetts General Hospital
Boston, Massachusetts 02114

More Details

Status
Recruiting
Sponsor
Stemline Therapeutics, Inc.

Study Contact

Stemline Trials
1-877-332-7961
clinicaltrials@menarinistemline.com