AZD6738 for Patients With Progressive MDS or CMML

This is a Phase Ib clinical trial. A Phase I clinical trial tests the safety of an investigational drug and also tries to define the appropriate dose of the investigational drug to use for further studies. "Investigational" means that the drug is being studied.

The FDA (the U.S. Food and Drug Administration) has not approved AZD6738 as a treatment for any disease.

AZD6738 is a a drug being studied as a potential treatment for individuals with Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia. It targets a specific pathway in cells that repairs damage to DNA, specifically by blocking a protein called ATR. ATR notices when there is injury to DNA, which is the blueprint that allows cells to function and replicate, and works to repair that damage. Studies done in a laboratory setting and cell lines suggest that MDS and CMML cells rely specifically on the ATR pathway to fix DNA damage and survive; by inhibiting ATR with AZD6738, MDS or CMML cells appear to selectively accumulate DNA damage and die, but healthy cells appear to be less sensitive to this target. This suggests that inhibiting ATR may be a way to selectively target MDS or CMML cells.

In this research study, the investigators are looking to first investigate the safety and tolerability of AZD6738. The investigators will also evaluate whether AZD6738 has any effect on tumor growth, measure the activity of AZD6738 in the bone marrow, and study how AZD6738 is cleared by the body.