Inclusion Criteria:

          -  Provision of written (signed) informed consent form (ICF) by the subject or legal
             guardian prior to the performance of any study-specific procedures, according to
             International Council on Harmonisation (ICH) and local regulatory requirements.
             Subject must be fully informed about their illness and the investigational nature of
             the study protocol (including foreseeable risks and possible toxicities) and must sign
             and date an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)
             approved informed consent form (ICF)(including Health Insurance Portability and
             Accountability Act authorization [HIPAA], if applicable) before performance of any
             study-specific procedures or examinations

          -  Subjects must be willing and able to comply with the protocol

          -  Subjects with AML or ALL, diagnosed according to the 2016 criteria by the World Health
             Organization (WHO) who are refractory or relapsed (any salvage) with no available
             therapies or not candidates for available therapies. For subjects with prior MDS or
             chronic myelomonocytic leukemia (CMML) or MPN who transformed to AML, therapy received
             for MDS, CMML, or MPN is NOT considered as prior therapy for AML except for MDS or
             CMML treated with HMAs. Subjects with MDS or CMML treated with HMA therapies who
             progress to AML and have no available therapies or are not candidates for available
             therapies, will be eligible at the time of progression to AML. In Phase 1: all R/R AML
             or R/R ALL subjects irrespective of mutations will be eligible. In Phase 2 Cohort A
             only R/R AML with MLLr will be eligible. In Phase 2 Cohort B only R/R AML with NPM1m
             will be eligible. In Phase 2 Cohorts C and D: Only R/R AML or R/R ALL subjects with an
             MLLr or NPM1m will be eligible

          -  Prior therapy with hydroxyurea, chemotherapy, biological or targeted therapy (e.g.
             FLT3 inhibitors, other kinase inhibitors), or hematopoietic growth factors is
             permitted

          -  Age 18 years or older

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2

          -  Total bilirubin =< 1.5 times upper limit of normal (x ULN)

          -  Aspartate aminotransferase or alanine aminotransferase =< 2.5 x ULN (aspartate
             aminotransferase or alanine aminotransferase =< 5.0 x ULN if deemed related to
             leukemia by the treating physician)

          -  Creatinine clearance >= 50 mL/min as calculated using the modified Cockcroft-Gault
             equation

          -  Serum electrolytes within the institution's normal limits: potassium, calcium (total
             calcium, calcium corrected for serum albumin in case of hypoalbuminemia or ionized
             calcium) and magnesium. If outside of the institution's normal range, subject will be
             eligible when electrolytes are corrected

          -  In the absence of rapidly progressive disease, the interval from prior treatment to
             the time of initiation of protocol therapy will be at least 14 days for prior
             anti-leukemic therapy with the exception of hydroxyurea as noted below OR at least 5
             half-lives for cytotoxic/noncytotoxic agents, whichever is shorter. The half-life for
             the therapy in question will be based on published pharmacokinetic literature
             (abstracts, manuscripts, investigator brochure's, or drug-administration manuals) and
             will be documented in the protocol eligibility document. Since the effect of therapy
             may be delayed, use of hydroxyurea for subjects with rapidly proliferative disease is
             allowed before the start of study therapy and on study and hydroxyurea will not
             require a washout

          -  Concurrent therapy for central nervous system (CNS) prophylaxis or continuation of
             therapy for controlled CNS disease is permitted. Subjects with a known history of CNS
             disease or leukemic brain metastasis must have been treated locally, have at least 3
             consecutive lumbar punctures (LPs) with no evidence of CNS leukemia, and must be
             clinically stable for at least 4 weeks prior to enrollment and have no ongoing
             neurological symptoms that in the opinion of the treating physician are related to the
             CNS disease (sequelae that are a consequence of the treatment of the CNS disease are
             acceptable)

          -  Females must be surgically or biologically sterile or postmenopausal (amenorrheic for
             at least 12 months) or if of childbearing potential, must have a negative serum or
             urine pregnancy test within 72 hours before the start of the treatment

          -  Women of childbearing potential must agree to use an adequate method of contraception
             during the study and until 4 months after the last treatment. Males must be surgically
             or biologically sterile or agree to use an adequate method of contraception during the
             study until 3 months after the last treatment. Adequate methods of contraception
             include:

               -  Total abstinence when this is in line with the preferred and usual lifestyle of
                  the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal,
                  postovulation methods) and withdrawal are not acceptable methods of
                  contraception.

               -  Female sterilization (have had surgical bilateral oophorectomy with or without
                  hysterectomy) or tubal ligation at least six weeks before taking study treatment.
                  In case of oophorectomy alone, only when the reproductive status of the woman has
                  been confirmed by follow up hormone level assessment

               -  Male sterilization (at least 6 months prior to screening). For female subjects on
                  the study, the vasectomized male partner should be the sole partner for that
                  subject

               -  Combination of any of the two following (a+b or a+c or b+c)

                    -  a. Use of oral, injected or implanted hormonal methods of contraception or
                       other forms of hormonal contraception that have comparable efficacy (failure
                       rate <1%), for example hormone vaginal ring or transdermal hormone
                       contraception.

                    -  b. Placement of an intrauterine device (IUD) or intrauterine system (IUS).

                    -  c. Barrier methods of contraception: Condom or Occlusive cap (diaphragm or
                       cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal
                       suppository.

               -  In case of use of oral contraception, women should have been stable on the same
                  pill before taking study treatment.

               -  Note: Oral contraceptives are allowed but should be used in conjunction with a
                  barrier method of contraception due to unknown effect of drug-drug interaction.
                  Women are considered post-menopausal and not of child-bearing potential if they
                  have had 12 months of natural (spontaneous) amenorrhea with an appropriate
                  clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have
                  had surgical bilateral oophorectomy (with or without hysterectomy) or tubal
                  ligation at least six weeks ago. In the case of oophorectomy alone, only when the
                  reproductive status of the woman has been confirmed by follow up hormone level
                  assessment is she considered not of child-bearing potential

        Exclusion Criteria:

          -  Subjects with a known allergy, hypersensitivity, or contraindication to the protocol
             therapies or any of their components to be used in the arm the subject is to be
             enrolled on

          -  Uncontrolled or significant cardiovascular disease, including any of the following:

               -  Bradycardia of less than 50 beats per minute, unless the subject has a pacemaker;

               -  Corrected QT interval Fridericia's Correction Formula (QTcF) interval > 450 msec;

               -  Diagnosis of or suspicion of long QT syndrome (including family history of long
                  QT syndrome);

               -  Systolic blood pressure >=180 mmHg or diastolic blood pressure >=110 mmHg;

               -  History of clinically relevant ventricular arrhythmias within 6 months prior to
                  screening (eg, ventricular tachycardia, ventricular fibrillation, or Torsade de
                  Pointes);

               -  History of second (Mobitz II) or third-degree heart block (subjects with
                  pacemakers are eligible if they have no history of fainting or clinically
                  relevant arrhythmias while using the pacemaker);

               -  History of uncontrolled angina pectoris, unstable angina or myocardial
                  infarction, coronary artery bypass graft (CABG), cerebrovascular accident (CVA),
                  transient ischemia attack (TIA), symptomatic pulmonary emboli within 6 months
                  prior to screening;

               -  New York Heart Association Class 3 or 4 heart failure;

               -  Left ventricular ejection fraction (LVEF) =< 50 or less than the institutional
                  lower limit of normal;

               -  Complete left bundle branch block (right bundle branch block is permitted, but
                  requires manual reading of the QTc interval);

               -  Active cardiac dysrhythmias of National Cancer Institute (NCI) Common Terminology
                  Criteria for Adverse Events (CTCAE) grade >= 2 (eg, atrial fibrillation)

          -  Persisting toxicity related to prior therapy of grade > 1 NCI-CTCAE v 5.0; however,
             alopecia and sensory neuropathy grade 2 or lower is acceptable

          -  Underwent HSCT within 90 days of the first dose of protocol therapy, or subjects with
             clinically significant (grade 2 or greater) graft-versus-host disease (GVHD) (the use
             of topical steroids for ongoing cutaneous GVHD is permitted)

          -  Subjects with symptomatic CNS leukemia or subjects with poorly controlled CNS leukemia

          -  Active and uncontrolled disease (active infection requiring systemic therapy, fever
             likely secondary to infection within prior 48 hours, uncontrolled hypertension despite
             adequate medical therapy as judged by the treating physician)

          -  Active (uncontrolled, metastatic) other malignancies

          -  Major surgery within 28 days prior to the first dose of protocol therapy

          -  Known dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the
             ingestion or gastrointestinal absorption of drugs administered orally

          -  Known history of testing positive for human immunodeficiency virus (HIV) or known
             acquired immunodeficiency syndrome (test at screening only if required by local
             regulations)

          -  Known history of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection with
             active Hepatitis B or C infection at screening (positive HBV surface antigen or HCV
             ribonucleic acid [RNA] if anti-HCV antibody screening test positive)

          -  Vaccination within 4 weeks of the first dose of study drug and while on trials is
             prohibited except for administration of inactivated vaccines

          -  Subjects who are currently receiving treatment with medication that meet one of the
             following criteria and that cannot be discontinued at least one week prior to the
             start of DS-1594b treatment:

               -  Medications that may prolong QTc interval and have a known risk of inducing
                  Torsades de Pointes unless it is vital for the care of the subjects

               -  Strong inhibitors or inducers of CYP3A

               -  CYP3A and CYP2C19 substrates with narrow therapeutic index

          -  Subjects who consume grapefruit products, Seville oranges, or star fruit within 3 days
             prior to the first DS-1594b administration and until the last day of DS-1594b is
             completed

          -  SUB-STUDIES: Subjects who are currently receiving moderate inhibitors or inducers of
             CYP3A who cannot discontinue at least one week prior to the start of DS-1594b
             treatment till the end of sub-study period

          -  SUB-STUDIES: Subjects who are currently receiving proton pump inhibitors who cannot
             discontinue at least 2 days prior to the start of DS-1594b treatment till the end of
             sub-study period

          -  Other severe acute or chronic medical conditions that is active and not well
             controlled including renal, skeletal muscle, adrenal insufficiency, colitis,
             inflammatory bowel disease, or psychiatric conditions including recent (within the
             past year) or active suicidal ideation or behavior; or laboratory abnormalities that
             may increase the risk associated with study participation or study treatment
             administration or may interfere with the interpretation of study results and, in the
             judgment of the investigator, would make the subject inappropriate for entry into this
             study

          -  Subjects unwilling or unable to comply with the protocol, including:

               -  Pregnant or breastfeeding women or women of childbearing potential who are unable
                  to comply with appropriate contraception as outlined in or who plan to become
                  pregnant while in the study or for at least 6-7 months after last administration
                  of study treatment

               -  Known alcohol or drug abuse within the last 1 year

               -  In a man whose sexual partner is a woman of childbearing potential, unwillingness
                  or inability to use an acceptable contraceptive method for the entire study
                  period and for at least 3 months after study completion

          -  Acute promyelocytic leukemia (APL)

          -  Uncontrolled or poorly controlled adrenal or pituitary disease (including adrenal
             insufficiency, Addison's disease, Cushing's disease)