Inclusion Criteria:

          1. Confirmed diagnosis of MDS, CMML, or AML. For the MDS expansion cohort, participants
             must be lower-risk MDS, defined as low or intermediate-1 risk categorization per
             International Prognostic Scoring System (IPSS) criteria that carries a missense SF3B1
             mutation at a variant allele frequency of 5 percent (%) or higher.

          2. The participant must meet the following criteria relevant to their specific diagnosis:

             A. Participants with higher-risk MDS/CMML must be intolerant of hypomethylating agents
             (HMAs) or not have responded to 4 treatment cycles of decitabine or 6 treatment cycles
             of azacitidine, or must have progressed at any point after initiation of an HMA.

             B. For dose escalation portion, participants with lower-risk MDS/CMML must be
             transfusion-dependent for red blood cells or platelets (as determined by instructional
             practices or local standard of care). For enrollment MDS expansion cohort, lower risk
             MDS participants must be RBC transfusion dependent according to IWG 2006 criteria
             (having received at least 4 units (U) of RBCs within 8 weeks for hemoglobin (Hb) of
             less than (<) 9 gram per deciliter (g/dL) prior to first dose of H3B-8800).
             Participants who are RBC transfusion-dependent must also have failed erythropoiesis
             stimulating agents (ESA) (primary resistance or relapse after a response) or have
             serum erythropoietin (EPO) levels greater than (>) 500 units per liter (U/L).

             C. Participants with AML must either refuse or not be considered candidates for
             intensive induction chemotherapy using consensus criteria for defining such
             participants. Previously treated participants should have evidence of persistent or
             recurrent AML in the peripheral blood and/or bone marrow that is refractory to, or has
             relapsed from, their most recent prior line of treatment. For AML, participants must
             have white blood cells (WBC) < 15*10^9/liter (L).

             D. Participants with CMML must have been treated with at least one prior therapy
             (hydroxyurea or a hypomethylating agent [HMA]).

          3. Eastern Cooperative Oncology Group (ECOG) performance score of 0-2.

          4. For expansion cohort- absolute neutrophil count (ANC) greater than or equal to (>=)
             500/ microliter (mcL) (0.5*10^9/L).

          5. For expansion cohort- platelet count >50,000/mcL (50*10^9/L).

          6. Adequate baseline organ function.

        Exclusion Criteria:

          1. Diagnosis of a core binding factor leukemia (t(8;21), t(16;16) or inv(16)).

          2. Participant is deemed candidate for hematopoietic stem cell transplants at the time of
             enrollment (for AML participants only).

          3. Family history of Leber Hereditary Optic Neuropathy, Autosomal Dominant Optic Atrophy,
             Late-Onset Retinal Degeneration, Familial Dysautonomia or other hereditary
             mitochondrial disease, unless the causative mutation(s) in the family have been
             determined and the participant has tested negative for the mutation(s).

          4. Known prior or current retinal or optic nerve disease (example, Retinitis Pigmentosa,
             diabetic retinopathy, optic neuritis) based on screening ophthalmology assessment for
             eligibility.

          5. Corrected vision is worse than 20/40 unless due to cataracts.

          6. Vitamin B12, folate or vitamin A deficiency. Rescreening following repletion therapy
             is acceptable.