A Study to Evaluate MK-0482 for Relapsed/Refractory Acute Myeloid Leukemia (AML) or Chronic Myelomonocytic Leukemia (CMML) (MK-0482-002)

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and recommended Phase 2 dose (RP2D) of MK-0482. There are 2 parts of this study. Part 1 is a dose escalation which will follow an accelerated titration design (ATD) for participants with relapsed/refractory (R/R) AML or CMML. Part 2 is a dose expansion for participants with R/R AML.

In Part 1, single participants will be enrolled sequentially into escalating dose levels. Progression from one dose level to the next higher dose level will be based on the evaluation of dose-limiting toxicity (DLT). Once a preliminary RP2D is identified in Part 1, approximately 10 to 15 additional participants with R/R AML will be enrolled at the RP2D for Part 2.

Eligibility Criteria:
Inclusion Criteria:

-Has confirmed diagnosis of AML with myelomonocytic or monoblastic/monocytic differentiation per World Health Organization (WHO) 2016 criteria and with confirmed refractory or relapsed disease (i.e., ≥5% blast in bone marrow or in peripheral blood) after treatment with available therapies known to benefit participant's AML subtypes or has a known diagnosis of CMML per WHO criteria \[2017\] with confirmed refractory or released disease after treatment with available therapies known to be active for CMML.

Exclusion Criteria:

* Has active central nervous system (CNS) leukemia.
* Has isolated extramedullary disease, i.e., no leukemic involvement in bone marrow or peripheral blood.
* Has diagnosis of acute promyelocytic leukemia or participants with known Philadelphia chromosome positive (Ph+) AML.
* Has received previous allogeneic stem cell transplant or organ transplant within 60 days of the start of study treatment.
* Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 1 year.
* Has a history of any of the following cardiovascular conditions within 6 months of screening: myocardial infarction, unstable angina, cerebrovascular accident, transient ischemic attack, coronary artery bypass graft, or pulmonary embolism; has New York Heart Association (NYHA) Class III or IV congestive heart failure.
* Has had a severe hypersensitivity reaction to treatment with a monoclonal antibody (mAB) and or any components of the study intervention, MK-0482.
* Has an active uncontrolled infection requiring directed therapy.
* Has immediately life-threatening, severe complications of leukemia such as uncontrolled bleeding, pneumonia with hypoxia or shock, or disseminated intravascular coagulation.
* Has known human immunodeficiency virus (HIV) and/or hepatitis B or C infections, or is known to be positive for HBsAg/ Hepatitis B virus (HBV) Deoxyribonucleic acid (DNA) or hepatitis C antibody or Ribonucleic acid (RNA).
* Has known psychiatric or substance abuse disorders (verbally reported) that would interfere with the participant's ability to cooperate with the requirements of the study.
* Is pregnant or breast feeding or expecting to conceive or father children within the projected duration of the study, starting with the Screening Visit through 120 days after the last dose of study intervention.
* Has received systemic anticancer therapy, radiotherapy, or surgery within 2 weeks before the start of study treatment.
* Has received hematopoietic cytokines (Granulocyte Colony Stimulating Factor (G-CSF), Granulocyte Macrophage (GM)-CSF, or erythropoietin) within 2 weeks prior to start of study treatment.
* Has received a live or live attenuated vaccine within 30 days before the first dose of study medication.
* Is currently participating and receiving study intervention in a study of an investigational agent or has participated and received study intervention in a study of an investigational agent or has used an investigational device within 14 days of administration of MK-0482.
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication.