Inclusion Criteria:

          -  Adult subjects ≥18 years of age who are able to understand and comply with study
             procedures, and provide written informed consent before any study-specific procedure.

          -  Cytologically or histologically confirmed diagnosis of MDS or CMML according to the
             2008 World Health Organization (WHO) classification.

          -  Performance status (ECOG) of 0-2.

          -  Previously treated MDS or CMML, defined as prior treatment with at least one
             hypomethylating agent (HMA; azacitidine and/or decitabine) for intermediate or high
             risk MDS or CMML whose disease progressed or relapsed as follows:

               1. Subject received HMA for at least 6 cycles and was still transfusion dependent
                  (as defined in 5b below).

               2. Subject had disease progression prior to Cycle 6 defined as ≥50% increase in bone
                  marrow blasts from pretreatment levels to >5%, or ≥2 g/dL reduction of Hgb from
                  pretreatment levels with transfusion dependence after at least 2 cycles of HMA.

        Other prior treatments for MDS such as lenalidomide, cytarabine, intensive chemotherapy,
        hydroxyurea, erythropoietin and other growth factors, or hematopoietic cell transplant
        (HCT) are allowed.

          -  Subjects must have either:

               1. Bone marrow blasts >5% at randomization, OR

               2. Transfusion dependence, defined as having had transfusion (in the setting of
                  active disease) of 2 or more units of RBC or platelets within 8 weeks prior to
                  randomization.

          -  Creatinine clearance or glomerular filtration rate ≥30 mL/min estimated by the
             Cockroft-Gault (C-G) or other medically acceptable formulas such as MDRD (Modification
             of Diet in Renal Disease) or CKD-EPI (the Chronic Kidney Disease Epidemiology
             Collaboration).

          -  Women of childbearing potential must not be pregnant or breastfeeding and must have a
             negative pregnancy test at screening. Women of childbearing potential and men with
             female partners of childbearing potential must agree to practice 2 highly effective
             contraceptive measures of birth control and must agree not to become pregnant or
             father a child while receiving treatment with guadecitabine, LDAC, or IC and for at
             least 3 months after completing treatment.

        Exclusion criteria:

          -  Subjects who have been diagnosed as having AML with peripheral blood or bone marrow
             blasts of ≥20%.

          -  Subjects who may still be sensitive to repeated treatment with decitabine or
             azacitidine such as subjects who had response to prior decitabine or azacitidine
             treatment, but relapsed >6 months after stopping treatment with these agents.

          -  Prior treatment with guadecitabine.

          -  Hypersensitivity to decitabine, guadecitabine, or any of their excipients.

          -  Second malignancy currently requiring active therapy, except breast or prostate cancer
             stable on or responding to endocrine therapy.

          -  Treated with any investigational drug within 2 weeks of the first dose of study
             treatment.

          -  Total serum bilirubin >2.5 ULN (except for subjects with Gilbert's Syndrome for whom
             direct bilirubin is <2.5×ULN), or liver cirrhosis or chronic liver disease Child-Pugh
             Class B or C.

          -  Known active HIV, HBV, or HCV infection. Inactive hepatitis carrier status or low
             viral hepatitis titer on antivirals is allowed.

          -  Known significant mental illness or other condition such as active alcohol or other
             substance abuse or addiction that, in the opinion of the investigator, predisposes the
             subject to high risk of noncompliance with the protocol.

          -  Refractory congestive heart failure unresponsive to medical treatment, active
             infection resistant to all antibiotics, or advanced non-MDS associated pulmonary
             disease requiring >2 liters per minute oxygen.

          -  Life expectancy of less than one month

          -  subjects with TP53 mutations