Print

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

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

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.