The purpose of this study is to evaluate a study drug called CFI-400945, either by itself or in combination with one of two chemotherapy drugs, known as azacitidine or decitabine. The study aims to determine how safe this drug is at different doses, with food, and in combination with azacitidine or decitabine, and to measure how well each combination works for acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or chronic myelomonocytic leukemia (CMML).

CFI-400945 is considered investigational, meaning has not been approved by the U.S. Food and Drug Administration (FDA) for the treatment of acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and Chronic Myelomonocytic Leukemia (CMML).

CFI-400945 is an oral (taken by mouth) drug that blocks the activity of a protein called Polo-like kinase 4 (PLK4). PLK4 is a protein that is important in regulating cell growth and division, and cell death. Many tumors are shown to make too much PLK4. When there is too much PLK4 produced, it is believed to contribute to uncontrolled cancer cell growth and division. Therefore, by blocking this protein from working, it is believed to stop tumors from growing or to cause them to shrink.

The study doctor will determine if participants receive CFI-400945, either by itself or in combination with as azacitidine or decitabine and at what dose.

Participants may continue to take the study drug for as long as they agree to continue in the study, if they do not experience any unacceptable side effects or the disease does not worsen.