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

Phase 2RecruitingNCT06456463

Stemline Therapeutics, Inc.83 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Acute Myeloid Leukemia

Interventions

Tagraxofusp

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (32)

University of California, Los Angeles

Los Angeles, California, United States

RECRUITING

Stanford Health Care

Stanford, California, United States

RECRUITING

University of Miami

Miami, Florida, United States

RECRUITING

AdventHealth Cancer Institute

Orlando, Florida, United States

Outcomes

Primary Outcomes

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)

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

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

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

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.

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

Parts 1 and 2: Duration of Response

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

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)

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.

Time frame: Cycles 1-4 (up to 112 days; 28 days/cycle)

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)

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.

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

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.

Time frame: Up to approximately 6 years

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.

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

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

Time frame: Up to approximately 6 years

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)

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)

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)

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.

Time frame: Up to approximately 6 years

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

Time frame: Up to approximately 6 years

Parts 1 and 2: Overall Survival

Time frame: Up to approximately 6 years

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)

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)

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)

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

Overview

Conditions

Interventions

Eligibility

Locations (32)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts