|Inclusion Criteria:||1) Subjects who are men or women, 18 years of age or older, with a confirmed diagnosis of IPSS intermediate-1, intermediate-2 or high-risk MDS including Chronic Myelomonocytic Leukemia (CMML) or AML. a) In the Dose Escalation Segment, subjects who are refractory, relapsed, or unresponsive to standard treatment will be the only ones allowed. b) In the Dose Expansion Segment, HMA treatment na´ve MDS subjects (including CMML), and intermediate-2 or high-risk MDS subjects (including CMML) relapsed or refractory to prior HMA treatment are allowed, and treatment na´ve AML subjects who are at least 65 years of age will be allowed if they also have at least one of the following criteria: 1) AML secondary to MDS, chemotherapy, or radiation therapy,|
2) **Continued from above. 2) poor cytogenetics defined as monosomies or partial deletions of chromosome 5 or 7 (del(5q), del(7q), -5, -7), abnormalities involving the long arm of chromosome 3 (q21;q26), t(6;9) (p23;q34), t(9;22) (q34;q11.2), or abnormalities including the long arm of chromosome 11 (11q23), or subjects with 3 or more unrelated cytogenetic abnormalities of any kind; 3) pre-existing clinically significant dysfunction of the heart (left ventricular ejection fraction [LVEF] < 50%) or lung (diffusing capacity of the lung for carbon monoxide [DLCO] or forced expiratory volume in the first second [FEV(1)] < 50% of expected) which is unrelated to the leukemia; 4) poor performance status, Eastern Cooperative Oncology Group (ECOG), of 2.
3) Subjects with ECOG performance status of 0 to 2.
4) Subjects with adequate organ function, defined as: a) Hepatic: Total bilirubin </= 2 X upper limit of normal (ULN); aspartate transaminase (AST/SGOT) and alanine transaminase (ALT/SGPT) </= 2.5 X ULN. b) Renal: serum creatinine </= 1.5 X ULN.
5) Women of child-bearing potential must not be pregnant or breastfeeding and must have a negative pregnancy test at screening. Woman of child-bearing potential and all men must be practicing two medically accepted methods of birth control. Women of non-childbearing potential are those having hysterectomy; bilateral oophorectomy; or menopause defined as no menses for at least 1 year AND either age >/= 65 years or follicle-stimulating hormone (FSH) levels in the menopausal range. Men should not father a child while receiving SGI-110 treatment and for 2 months following completion of treatment.
6) For subjects with prior allogeneic stem cell transplant, no evidence of active graft-versus host disease (GVHD) and must be >/= 2 weeks off immunosuppressive therapy.
7) Subjects with no major surgery within 4 weeks of first dose of SGI-110.
8) Subjects with no chemotherapy within 2 weeks of first dose of SGI-110 (minimum of 6 weeks for nitrosoureas and 8 weeks for bone marrow transplantation) with the exception of hydroxyurea which will be allowed during Course 1 of treatment.
9) Subjects who sign an approved informed consent form for the study.
10) Subjects who are willing to comply with the protocol.