The purpose of this research study is to test the safety and efficacy of a new drug combination with three agents, azacitidine, venetoclax and tagraxofusp. Leftover (residual) leukemia disease that is not visible by eye can be increase the chance of disease recurrence. This research study is to determine if the combination therapy can safely help to control residual Acute Myeloid Leukemia (AML) and to prevent disease recurrence.
The names of the study drugs involved in this study are:
* Tagraxofusp (a type of CD123-directed cytotoxin) * Azacitidine (a type of standard of care cytidine nucleoside analog) * Venetoclax (a type of standard of care BCL-2 inhibitor)
Age ≥ 18 years.
History of known diagnosis of Acute Myeloid Leukemia (including de novo, secondary or AML arising from MDS).
Subjects must be in CR, CRi, or CRh with <5% morphologic blasts in bone marrow
Any evidence of CD123+ by central assessment.
Prior treatment with CD123-targeted therapy
Known diagnosis of acute promyelocytic leukemia.
Subjects who received intensive anti-leukemic chemotherapy within 2 weeks from first dose of study. If on venetoclax, subjects must be off venetoclax for at least 5 days
Subjects pre-arranged for SCT are only excluded if it is imminent.
Sequential
Tagraxofusp
DrugA CD123-directed cytotoxin, Single-use vial, via intravenous (into the vein) infusion per protocol.
Azacitidine (AZA)
DrugA cytidine nucleoside analog, single-use vial, via intravenous infusion or subcutaneous (under the skin) injection per standard of care.
Venetoclax
DrugA BCL-2 inhibitor, tablet, via orally per standard of care.
Recommended phase II dose (RP2D) of tagraxofusp in combination with fixed dose of Azacitidine and Venetoclax [Phase I]
Definition of RP2D is outlined in protocol section 5.4.
Number of Participants Experienced Dose-Limiting Toxicity (DLT) [Phase I]
Definition of Dose Limiting Toxicity (DLT) is outlined in protocol section 5.4.
Measurable Residual Disease (MRD) conversion rate [Phase II]
MRD conversion rate is defined as the proportion of participants that achieve multi-parametric flow cytometry (MFC) MRD conversion (positive to negative) within the first four cycles of therapy. MRD negativity will be defined according to 2021 ELN MRD Working Party Consensus Guidelines and central lab MRD will be used to make this determination: CR with negative MFC-MRD negative refers to achievement of flow MRD negativity: MFC-MRD negative in bone marrow defined as \<0.1% (same as \<10\^-3).
Duration of Remission (DOR)
DOR based on Kaplan-Meier method is measured from the time criteria are met for complete remission (CR) and partial remission (PR) until the first data that recurrent or disease progression. Response criteria is listed in Appendix D.
Median Overall Survival (OS)
Overall Survival (OS) based on Kaplan-Meier method is defined as the time from study treatment to death due to any cause or censored at date last known alive. All surviving participants will be censored at time of final follow up.
Median Relapse-free survival (RFS)
Relapse-Free Survival (RFS) is defined as the time from study treatment to evidence of relapse (morphologic relapse per ELN 2022 criteria) or at death due to any cause including underlying disease. Participants alive without disease progression are censored at date of last follow up.
Median Event-free Survival (EFS)
Event-free survival is defined as the number of days from the date of treatment initiation (i.e., C1D1) to the date of documented treatment failure, relapse (MRD or morphologic), progression, or death from any cause, whichever occurs first, and will be calculated for all participants. If neither disease progression nor death is documented prior to study termination, analysis cutoff, or the start of confounding anticancer therapy, these endpoints will be censored at the date of last tumor assessment date.
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Jacqueline Garcia, MD
Lead sponsor
Dana-Farber Cancer Institute
Sponsor institution
Stemline Therapeutics, Inc.
Collaborator
Break Through Cancer Foundation
Collaborator
