Inclusion Criteria:

          1. Has morphologically confirmed diagnosis of myelodysplastic syndromes (MDS) or CMML
             (i.e., with white blood cell [WBC] <13,000/microliter [mcL]) or low-blast acute
             myelogenous leukemia (AML).

          2. Has MDS or CMML and must also have one of the following Prognostic Risk Categories,
             based on the Revised International Prognostic Scoring System (IPSS-R):

               -  Very high (>6 points).

               -  High (>4.5-6 points).

               -  Intermediate (>3-4.5 points): a participant determined to be in the Intermediate
                  Prognostic Risk Category is only allowable in the setting of >=5% bone marrow
                  myeloblasts.

          3. Eastern Cooperative Oncology Group (ECOG) status of 0, 1, or 2.

          4. Participants with AML (20%-30% blasts) must have a treatment-related mortality (TRM)
             score >=4 for intensive, induction chemotherapy as calculated using the simplified
             model described by Walter and coworkers.

        Calculation of TRM score:

          -  0 for (age <61 years), +2 for (age 61-70 years), +4 for (age >=71 years).

          -  + 0 for (PS=0), +2 for (PS=1), +4 for (PS >1).

          -  + 0 for (platelets <50), +1 for (platelets >=50).

        Exclusion Criteria:

          1. Has previous treatment for HR MDS or CMML or low-blast AML with chemotherapy or other
             antineoplastic agents including hypomethylating agent (HMAs) such as decitabine or
             azacitidine. Previous treatment is permitted with hydroxyurea and with lenalidomide,
             except that lenalidomide may not be given within 8 weeks before the first dose of
             study drug.

          2. Has acute promyelocytic leukemia as diagnosed by morphologic examination of bone
             marrow, by fluorescent in situ hybridization or cytogenetics of peripheral blood or
             bone marrow, or by other accepted analysis.

          3. Participants with AML with a WBC count >50,000/mcL. Participants who are cytoreduced
             with leukapheresis or with hydroxyurea may be enrolled if they meet the eligibility
             criteria.

          4. Is eligible for intensive chemotherapy and/or allogeneic stem cell transplantation.
             The reason a participant is not eligible for intensive chemotherapy and/or allogeneic
             stem cell transplantation may consist of one or more of the following factors:

               -  Age >75.

               -  Comorbidities.

               -  Inability to tolerate intensive chemotherapy (e.g., participants with AML with
                  20%-30% blasts and TRM >=4).

               -  Physician decision (e.g., lack of available stem cell donor).

               -  The reason a participant is not eligible should be documented in the electronic
                  case report form (eCRF).

          5. Has either clinical evidence of or history of central nervous system involvement by
             AML.

          6. Has active uncontrolled infection or severe infectious disease, such as severe
             pneumonia, meningitis, or septicemia.

          7. Is diagnosed or treated for another malignancy within 2 years before randomization or
             previously diagnosed with another malignancy and have any evidence of residual
             disease.

          8. Has nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they
             have undergone resection.

          9. Has prothrombin time (PT) or aPTT >1.5× upper limit of normal (ULN) or active
             uncontrolled coagulopathy or bleeding disorder. Participants therapeutically
             anticoagulated with warfarin, direct thrombin inhibitors, direct factor Xa inhibitors,
             or heparin are excluded from enrollment.

         10. Has known human immunodeficiency virus (HIV) seropositive.

         11. Has known hepatitis B surface antigen seropositive, or known or suspected active
             hepatitis C infection. Note: Participants who have isolated positive hepatitis B core
             antibody (i.e., in the setting of negative hepatitis B surface antigen and negative
             hepatitis B surface antibody) must have an undetectable hepatitis B viral load.

         12. Has known hepatic cirrhosis or severe preexisting hepatic impairment.

         13. Has known cardiopulmonary disease defined as unstable angina, clinically significant
             arrhythmia, congestive heart failure (New York Heart Association Class III or IV),
             and/or myocardial infarction within 6 months before first dose, or severe pulmonary
             hypertension.

         14. Has treatment with strong cytochrome P 3A (CYP3A) inducers within 14 days before the
             first dose of pevonedistat.