Venetoclax + Azacitidine + Eganelisib for Acute Myeloid Leukemia

(GAVEL Trial)

This trial explores a new combination treatment for people with acute myeloid leukemia (AML), a type of blood cancer. It adds a drug called eganelisib (a PI3K-gamma inhibitor) to the standard drugs venetoclax and azacitidine to assess safety and effectiveness. The trial targets those with AML who have not responded to other treatments or have newly diagnosed high-risk AML and cannot undergo intense chemotherapy. Participants should have AML affecting their bone marrow and be able to attend regular clinic visits for treatment and follow-up.

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 therapy.

The trial requires that you stop taking certain medications, specifically moderate or strong inhibitors or inducers of CYP2C8 and CYP3A4, P-glycoprotein inhibitors, and breast cancer resistance protein inhibitors, at least 14 days before starting the study and throughout its duration. You should discuss your current medications with the study team to see if any need to be adjusted.

Earlier studies have shown that eganelisib, when used alone, produces promising results in treating certain blood cancers like acute myeloid leukemia (AML). It was generally well-tolerated, but further research is needed to fully understand its safety.

Research has found that venetoclax is usually safe when combined with azacitidine for treating AML. However, some patients may experience serious side effects, such as pneumonia and other infections. These risks are important to consider when thinking about joining a trial.

Azacitidine, on its own, is a common treatment for AML and is generally well-tolerated. The most common issues include low blood cell counts and infections, but these are often manageable.

Researchers are excited about the combination of Venetoclax, Azacitidine, and Eganelisib for treating Acute Myeloid Leukemia (AML) because it introduces a novel approach by combining these three drugs. Eganelisib is a unique addition, targeting the PI3K-gamma pathway, which is not commonly targeted by standard AML treatments. This pathway plays a significant role in the immune system, potentially enhancing the body’s ability to fight cancer cells. The combination aims to improve effectiveness by attacking the cancer through multiple mechanisms, offering hope for better outcomes compared to traditional chemotherapy or single-drug regimens.

Studies have shown that combining venetoclax and azacitidine effectively treats acute myeloid leukemia (AML). This combination has been linked to better survival rates and higher remission rates compared to standard treatments. In this trial, participants will receive venetoclax, azacitidine, and eganelisib. Research suggests that adding eganelisib, a drug that blocks a specific protein in cancer cells to stop their growth, might enhance the treatment further. Experience with the venetoclax and azacitidine pair indicates that nearly 90% of some patients achieve complete remission. The researchers aim to boost these results by using eganelisib to further inhibit cancer cell growth.⁶⁷⁸⁹¹⁰