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

Acute Myeloid Leukemia Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06456463
• Other study ID #: STML-401-0423
• Secondary ID: 2024-514660-48-0
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: August 30, 2024
• Est. completion date: February 11, 2030

Study information

• Verified date: June 2024
• Source: Stemline Therapeutics, Inc.
• Contact: Stemline Trials
• Phone: 1-877-332-7967
• Email: clinicaltrials[@]menarinistemline.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will be divided into 2 parts (Part 1 and Part 2). Part 1 will evaluate 2 doses of tagraxofusp, 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. Both parts will be conducted in participants with previously untreated CD123+ AML who are ineligible for intensive chemotherapy.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 76
• Est. completion date: February 11, 2030
• Est. primary completion date: February 9, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

Key Inclusion Criteria:

• Histologically confirmed newly diagnosed AML with bone marrow blast count =20%.
• Participant has any level of CD123 expression on blasts determined centrally by flow cytometry.
• For participants between 60 and 74 years of age, 1 of the following comorbidities is

required:

• Eastern Cooperative Oncology Group (ECOG) Score of 2 or 3.
• Diffusing capacity of lung for carbon monoxide of =65% or forced expiratory volume of 1 second =65%.
• Creatinine clearance =30 to <45 milliliters/minute.
• Moderate hepatic impairment with total bilirubin >1.5 to =3.0 x upper limit of normal.
• Any other comorbidity that the physician judges to be incompatible with intensive chemotherapy must be reviewed and approved by the Sponsor and Medical Monitor prior to enrollment.
• ECOG performance status:
• If =75 years of age, ECOG 0 to 2
• If =60 to 74 years of age, ECOG 0 to 3

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 any of the following:
• 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.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• Tagraxofusp
Tagraxofusp will be administered by intravenous infusion.
• Venetoclax
Venetoclax will be administered as an oral tablet.
• Azacitidine
Azacitidine will be administered subcutaneously or by intravenous infusion.

Locations

Country	Name	City	State
United States	Dana Farber Cancer Institute (DFCI)	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Baylor Scott & White Health	Dallas	Texas
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	University of California, Los Angeles	Los Angeles	California
United States	Mt. Sinai - Ruttenberg Treatment Center	New York	New York
United States	Washington University - Siteman Cancer Center	Saint Louis	Missouri
United States	Hunstman Cancer Institute	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Stemline Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Secondary	Parts 1 and 2: Number of Participants Achieving a BOR of CR		Cycles 1-6 (up to 168 days; 28 days/cycle)
Secondary	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)
Secondary	Parts 1 and 2: Duration of Response		Cycles 1-6 (up to 168 days; 28 days/cycle)
Secondary	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)
Secondary	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)
Secondary	Parts 1 and 2: Number of Participants Achieving a BOR of CR or CRi		Cycles 1-6 (up to 168 days; 28 days/cycle)
Secondary	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)
Secondary	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
Secondary	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)
Secondary	Parts 1 and 2: Number of Participants Who Bridged to Stem Cell Transplant (SCT) Through Study Treatment		Up to approximately 6 years
Secondary	Parts 1 and 2: Plasma Concentration of Free Tagraxofusp, Venetoclax, and Azacitidine		Predose, up to 8 hours post dose (Days 4, 5, 6, 7, 14; Cycles 1-6; 28 days/cycle)
Secondary	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)
Secondary	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