A Study to Assess the Effect of CC-95251 in Participants With Acute Myeloid Leukemia and Myelodysplastic Syndromes

Inclusion Criteria:

• Eastern Cooperative Oncology Group Performance Status of 0 to 2

For Parts A \& B:

* Relapsed or refractory (R/R) acute myeloid leukemia (AML) as defined by the 2016 WHO Classification
* R/R myelodysplastic syndromes (MDS) as defined by the 2016 WHO Classification with intermediate, high or very high risk by Revised International Prognostic Scoring System (IPSS-R)

For Part C:

• Treatment-naïve (TN) (ie, previously untreated) MDS as defined by the 2016 WHO Classification with intermediate, high or very high risk by IPSS-R

For Part D:

• TN AML as defined by the 2016 WHO Classification, including secondary AML and therapy-related AML in participants who are ineligible (IE) for intensive chemotherapy (IC) and allogeneic hematopoietic stem cell transplant (HSCT)

Exclusion Criteria:

* Acute promyelocytic leukemia
* Immediately life-threatening, severe complications of leukemia such as disseminated/uncontrolled infection, uncontrolled bleeding, and/or uncontrolled disseminated intravascular coagulation
* Participants who have received prior treatment with a CD47 or SIRPα targeting agent
* Participant is on chronic systemic immunosuppressive therapy or corticosteroids
* Prior systemic cancer-directed treatments or investigational modalities ≤ 5 half-lives or 4 weeks prior to starting study treatment, whichever is shorter (relapsed or refractory participants only).
* Any condition including, active or uncontrolled infection, or the presence of laboratory abnormalities, which places the participant at unacceptable risk if he/she were to participate in the study
* Pregnant or nursing participants.

Other protocol-defined inclusion/exclusion criteria apply