Clinical trial NCT06456463: A Study of Tagraxofusp in Combination With Venetoclax and Azacitidine in Adults With Untreated CD123+ Acute Myeloid Leukemia Who Cannot Undergo Intensive Chemotherapy
Official 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Acute Myeloid Leukemia
Keywords: CD123+
Tagraxofusp
Venetoclax
Azacitidine
Lead sponsor: Stemline Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2024-06-13
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
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

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.


Eligibility criteria: 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 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.

Key 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.

Primary outcomes:
measure: Part 1: Determination of Part 2 Selected Dose of Tagraxofusp When Administered in Combination with Venetoclax and Azacitidine
timeFrame: Cycles 1-4 (up to 112 days; 28 days/cycle)
measure: Part 2: Number of Participants Achieving a Best Overall Response (BOR) of Complete Remission (CR)
timeFrame: Cycles 1-4 (up to 112 days; 28 days/cycle)
Secondary outcomes:
measure: Parts 1 and 2: Number of Participants Achieving a BOR of CR
timeFrame: Cycles 1-6 (up to 168 days; 28 days/cycle)
measure: Parts 1 and 2: Time to First CR
timeFrame: Cycles 1-6 (up to 168 days; 28 days/cycle)
measure: Parts 1 and 2: Duration of Response
timeFrame: Cycles 1-6 (up to 168 days; 28 days/cycle)
measure: 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)
timeFrame: Cycles 1-4 (up to 112 days; 28 days/cycle)
measure: Parts 1 and 2: Time to First Composite CR
timeFrame: Cycles 1-4 (up to 112 days; 28 days/cycle)
measure: Parts 1 and 2: Number of Participants Achieving a BOR of CR or CRi
timeFrame: Cycles 1-6 (up to 168 days; 28 days/cycle)
measure: Parts 1 and 2: Time to first CR/CRi
timeFrame: Cycles 1-6 (up to 168 days; 28 days/cycle)
measure: Parts 1 and 2: Event-free Survival (EFS)
timeFrame: Up to approximately 6 years
measure: Parts 1 and 2: CR with Minimal Residual Disease (MRD) Negative
timeFrame: Cycles 1-6 (up to 168 days; 28 days/cycle)
measure: Parts 1 and 2: Number of Participants Who Bridged to Stem Cell Transplant (SCT) Through Study Treatment
timeFrame: Up to approximately 6 years
measure: Parts 1 and 2: Plasma Concentration of Free Tagraxofusp, Venetoclax, and Azacitidine
timeFrame: Predose, up to 8 hours post dose (Days 4, 5, 6, 7, 14; Cycles 1-6; 28 days/cycle)
measure: Parts 1 and 2: Number of Participants With Serum Anti-drug Antibodies for Tagraxofusp, Venetoclax, and Azacitidine
timeFrame: Day 4 of each cycle (each cycle is 28 days) up to the end of study (approximately 6 years)
measure: Parts 1 and 2: Exposure-response of Free Tagraxofusp When Administered in Combination with Venetoclax and Azacitidine
timeFrame: Up to approximately 6 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
city: Palo Alto
country: United States
facility: Stanford University Medical Center
state: California
city: Miami
country: United States
facility: University of Miami Sylvester Comprehensive Cancer Center
state: Florida
city: Orlando
country: United States
facility: AdventHealth Cancer Institute
state: Florida
city: Boston
country: United States
facility: Dana Farber Cancer Institute (DFCI)
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health
state: Michigan
city: Saint Louis
country: United States
facility: Washington University - Siteman Cancer Center
state: Missouri
city: Hackensack
country: United States
facility: John Theurer Cancer Center - Hackensack Meridian Health
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute
state: New Jersey
city: Buffalo
country: United States
facility: Roswell Park Comprehensive Cancer Center
state: New York
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
city: Charlotte
country: United States
facility: Novant Health Presbyterian Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Novant Health Derrick L Davis Cancer Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Philadelphia
country: United States
facility: Sydney Kimmel (Thomas Jefferson University)
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon, the Cancer Institute of HCA Healthcare
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Dallas
country: United States
facility: Baylor Scott & White Health
state: Texas
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Concord
country: Australia
facility: Concord Repatriation General Hospital
state: New South Wales
city: Townsville
country: Australia
facility: Townsville Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Box Hill
country: Australia
facility: Box Hill Hospital
state: Victoria
city: Clayton
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Fitzroy
country: Australia
facility: St. Vincents Hospital
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Hospital
state: Victoria
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
Study officials:
References: