Mass General - Division of Clinical Research

Participants must satisfy the criteria below to be enrolled in the Dose Escalation (Part A) or the Dose Expansion (Part B) of this study. - Participant is ≥ 18 years of age, at the time of signing the ICF. - Participant must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted. - Participant is willing and able to adhere to the study visit schedule and other protocol requirements. - Relapsed or refractory acute myeloid leukemia (R/R AML) and relapsed or refractory higher-risk myelodysplastic syndromes (R/R HR-MDS) as defined by the World Health Organization (WHO) criteria who have failed or are ineligible for all available therapies which may provide clinical benefit - Participant has Eastern Cooperative Oncology Group Performance Status of 0 to 2. - Participants must have the following screening laboratory values: - Total White Blood Cell count (WBC) < 25 x 109/L prior to first infusion. - Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) ≤ 3.0 x upper limit of normal (ULN), unless considered due to leukemic organ involvement, in which case AST and ALT can be ≤ 5.0 x ULN. - Uric acid ≤ 7.5 mg/dL (446 μmol/L). - Serum total bilirubin ≤ 1.5 x ULN, unless considered due to Gilbert's syndrome - Estimated serum creatinine clearance of ≥ 60 mL/min using the Cockcroft-Gault equation. Measured creatinine clearance from a 24-hour urine collection is acceptable if clinically indicated. - INR < 1.5 x ULN and partial thromboplastin time (PTT) < 1.5 x ULN.

The presence of any of the following will exclude a participant from enrollment: - Participant has any condition, including active or uncontrolled infection, or the presence of laboratory abnormalities, which places the participant at unacceptable risk if the participant were to participate in the study. - Any other significant medical condition, laboratory abnormality, or psychiatric illness which places the participant at unacceptable risk if he/she were to participate in the study or that would prevent the participant from complying with the study. - Participant has any condition that confounds the ability to interpret data from the study. - Participants with acute promyelocytic leukemia. - Participants with clinical symptoms suggesting active central nervous system (CNS) leukemia or known CNS leukemia. - Participants with immediately life-threatening, severe complications of leukemia such as disseminated/uncontrolled infection, uncontrolled bleeding, and/or uncontrolled disseminated intravascular coagulation. - Participants with impaired cardiac function or clinically significant cardiac diseases, - Participants who have undergone major surgery ≤ 2 weeks prior to starting CC-91633. Participants must have recovered from any clinically significant effects of recent surgery. - Pregnant or nursing individuals. - Participants with known human immunodeficiency virus infection. - Participants with known chronic, active hepatitis B virus or hepatitis C virus C (HCV) infection. - Participants with ongoing treatment with chronic, therapeutic dosing of anticoagulants (eg, warfarin, low molecular weight heparin, Factor Xa inhibitors). - Participants with history of concurrent second cancers requiring active, ongoing systemic treatment - Participants with clinically significant diarrhea, vomiting or malabsorption felt to limit absorption of orally administered medications. - Participants with known or suspected hypersensitivity to any of the components or excipients of the study treatment or to similar class drugs (eg, lenalidomide).