Inclusion Criteria:

          -  Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2

          -  Adequate organ function (bone marrow, hepatic, renal, cardiovascular)

          -  Left ventricular ejection fraction of ≥50%

          -  Female patients of childbearing potential must have a negative pregnancy test within 7
             days of the start of treatment and must agree to use a highly effective method of
             contraception during the trial

          -  Patients must have recovered from the effects of any prior cancer related therapy,
             radiotherapy or surgery (toxicity ≤ Grade 1)

          -  All patients on prior investigational agents must wait at least 5 half-lives of the
             agent in question, or 14 days, whichever is longer before study entry

          -  AML patients only: Pathologically confirmed diagnosis of AML as defined by the WHO
             Classification and patients with targeted mutations must have been treated with
             appropriate therapy for their disease

               -  White blood cell count < 25 x 10^9/L. Hydrea or leukapheresis are permitted to
                  meet this criterion.

          -  CMML patients only: intermediate-2 or high risk per CMML-specific prognostic scoring
             system (CPSS) or clinical/molecular CPSS (CPSS-mol) criteria. Must have failed prior
             therapy with a hypomethylating agent.

          -  MDS patients only: Intermediate, high, or very high risk by International Prognostic
             Scoring System-Revised [IPSS-R] criteria that is relapsed or refractory to approved
             therapies or MDS/MPN Overlap Syndrome (displaying both fibrosis and dysplastic
             features).

          -  NHL patients only: Histologically or cytologically confirmed NHL, including B- and
             T-cell lymphomas that is relapsed or refractory or intolerant to approved therapies.
             Must have one lesion that can be measured for response

          -  MM patients only: Measurable disease defined by one or more of the following: Serum
             M-protein ≥ 0.5 g/dL, Urine M-protein ≥ 200 mg/24 hours, Serum Free Light Chain (sFLC)
             > 10 mg/dL with normal serum FLC ratio. Presence of soft tissue plasmacytoma confirmed
             by imaging

          -  NHL and MM patients only: must have the following lab values within 14 days prior to
             study Day 1:

               -  ANC ≥1.0 x 10^3 μL

               -  Platelet count ≥50,000 μL

        Exclusion Criteria:

          -  Known hypersensitivity to any of the components of PRT1419

          -  Female patients who are pregnant or lactating

          -  Mean QTcF interval of >480 msec

          -  History of heart failure, additional risk factors for arryhthmias or requiring
             concomitant medications that prolong the QT/QTc interval

          -  Hematopoietic stem-cell transplant < 90 days or have GVHD Grade >1 at study entry

          -  Uncontrolled intercurrent illnesses

          -  Treatment with strong inhibitors of CYP2C8 and/or P-glycoprotein for which there are
             no therapeutic substitutions

          -  Inflammatory disorders of the gastrointestinal tract, or subjects with GI
             malabsorption

          -  HIV positive; known active hepatitis B or C

          -  Prior exposure to an MCL1 inhibitor

          -  History of another malignancy except:

               -  Malignancy treated with curative intent with no known active disease for >2 years
                  at study entry

               -  Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
                  of disease

               -  Adequately treated carcinoma in situ without evidence of disease

               -  Other concurrent low-grade malignancies (i.e chronic lymphocytic leukemia (Rai
                  0)) may be considered after consultation with Sponsor.