This is a phase 1 study of investigational drug CFI-400945 in patients with relapsed or refractory acute myeloid leukemia or myelodysplastic syndrome. The purpose of this phase 1 study is to see how safe and tolerable the study drug is and to determine the best dose (maximum tolerated dose or recommended phase 2 dose) that can be given in this patient population.

Participants will be screened prior to the start of the study drug for eligibility.

Eligible participants will take CFI-400945 by mouth, once a day, every day of each 28 day cycle. Participants will be asked to keep a study drug diary.

While receiving the study drug, participants will have standard tests and procedures done for safety purposes.

Procedures for research purposes include bone marrow aspirate and additional blood collection for biomarker research, and additional blood samples for pharmacokinetic research.

When participants stop the study drug permanently for any reason, they will be asked to have an End of Treatment Visit and be followed for safety purposes.

Inclusion Criteria:

• 18 years of age or older
• Relapsed and/or refractory myeloid leukemia (AML) or myelodysplastic syndrome (MDS) that meets certain criteria for prior treatments
• Have acceptable circulating blasts count
• Have clinically acceptable laboratory blood and urine test results
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
• Be able to swallow oral medications
• Have a life expectancy of 3 months or more
• Agree to use highly effective means of contraception during a defined period
• Negative serum pregnancy test before the start of the study drugs
• Have the ability to understand the requirements of the study, provide written informed consent which includes authorization for release of protected health information, abide by the study restrictions, provide a blood and bone marrow sample for genetic testing and agree to return for the required assessments

Exclusion Criteria:

• Have received cancer therapies within 14 days or 5 half-lives (whichever is shorter) prior to first dose of study drug or have not recovered from toxicities from prior treatments
• Not recovered from toxicities related to allogeneic transplant
• Known active extramedullary central nervous system (CNS) AML
• Secondary cancer needing therapy with exceptions
• Known active human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infection
• Known significant mental illness or other condition that may affect the ability to follow the requirements of the study
• Have a chronic infection
• Have uncontrolled severe hypertension
• Have symptomatic congestive heart failure
• Have active angina pectoris or recent myocardial infarction
• Have chronic atrial fibrillation or unacceptable QTc
• Have had major surgery within 21 days of starting therapy
• Have additional uncontrolled serious medical or psychiatric illness
• Have any medical condition that would affect taking the study drug
• Receiving treatment with full dose warfarin
• Receiving treatment with drugs not allowed in this study
• Women who are pregnant or lactating.