Tagraxofusp + Venetoclax + Azacitidine for Acute Myeloid Leukemia

This trial tests a new combination of three drugs—azacitidine, venetoclax, and tagraxofusp (an experimental treatment)—to determine if they can safely manage residual leukemia cells in individuals with Acute Myeloid Leukemia (AML). The goal is to prevent the disease from returning. It targets those diagnosed with AML who are in a specific stage of remission (CR, CRi, or CRh) with some leukemia cells still present. Participants must have a history of AML, not have undergone recent intensive chemotherapy, and must not have used CD123-targeted therapy before. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

The trial protocol does not specify if you need to stop taking your current medications, but you must stop taking venetoclax at least 5 days before starting the study. Also, you should not take any moderate or strong CYP3A inducers within 7 days of starting the study.

Previous studies found that combining tagraxofusp, azacitidine, and venetoclax is safe. These studies did not show an increased risk of capillary leak syndrome (where fluid leaks from small blood vessels) or infections when used together. Patients tolerated higher doses without severe side effects, suggesting this combination might be safe for people with acute myeloid leukemia (AML).

Researchers are excited about the combination of Tagraxofusp, Venetoclax, and Azacitidine for treating Acute Myeloid Leukemia (AML) because it offers a novel approach by combining different mechanisms of action. Unlike traditional treatments like chemotherapy, which broadly attack cancer cells, Tagraxofusp specifically targets a protein expressed on the surface of certain leukemia cells, potentially improving precision and reducing harm to healthy cells. Venetoclax disrupts cancer cell survival pathways, while Azacitidine works to modify DNA, making cancer cells more susceptible to treatment. This multi-pronged strategy might enhance effectiveness and lead to better outcomes for patients with AML.

This trial will evaluate the combination of tagraxofusp, venetoclax, and azacitidine for treating Acute Myeloid Leukemia (AML). Research has shown that this combination may effectively reduce cancer levels in the body and help eliminate hidden leukemia cells. Participants will receive these drugs in two phases: a Phase 1 dose escalation to determine the maximum tolerated dose and a Phase 2 dose expansion to further assess efficacy. Venetoclax and azacitidine are already commonly used to treat AML due to their effectiveness, while tagraxofusp targets a protein called CD123 on leukemia cells, providing an additional method to attack the cancer. This combination aims to improve outcomes by reducing the chances of the disease returning, while remaining manageable and not significantly increasing serious side effects like capillary leak syndrome or infections.³⁴⁵⁶⁷