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
Part 1 Primary:
The primary objective of Part 1 is to determine the Part 2 Selected Dose of tagraxofusp (Tag) in combination with venetoclax and azacitidine (Ven/Aza) in previously untreated CD123+ AML subjects who are ineligible for intensive chemotherapy.
Part 2 Primary:
The primary objective of Part 2 is to evaluate the complete remission (CR) rate within the first 4 cycles of Tag in combination with Ven/Aza in previously untreated CD123+ AML subjects who are ineligible for intensive chemotherapy.
Part 1 Secondary:
The secondary objectives of Part 1 include the following:
Characterize the safety of Tag in combination with Ven/Aza;
Evaluate the clinical efficacy of Tag in combination with Ven/Aza as measured in terms of:
o CR within the first 4 cycles and within the first 6 cycles
o Time to first CR, duration of response (DOR)
o Composite CR rate (CR, complete remission with incomplete hematologic recovery [CRi],
complete remission with partial hematologic recovery [CRh]) within the first 4 cycles,
time to first composite CR, duration of composite CR
o CR/CRi rate within the first 4 cycles and within first 6 cycles
o Time to first CR/CRi, duration of CR/CRi response
o Event-free survival (EFS)
o Rate of minimal residual disease (MRD) negativity
o Overall survival (OS)
Evaluate the rate of hematopoietic stem cell transplant (SCT) in subjects treated with Tag in
combination with Ven/Aza;
Evaluate the pharmacokinetics of free Tag and immunogenicity in combination with Ven/Aza;
Evaluate the pharmacokinetics of Ven/Aza in combination with Tag;
Evaluate the exposure-response for efficacy and safety of free Tag/Ven/Aza in comparison with Ven/Aza historical data;
TAGRAXOFUSP (TAG)
Venetoclax (ABT-199)
- Rutgers University
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.
Please note that we have obtained the inclusion and exclusion criteria information from the National Institutes of Health’s clinical trials web site ClinicalTrials.gov. The listed criteria may not necessarily reflect recent amendments to the protocol and the current criteria.
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