| | Requirement |
| 1 | Confirmed diagnosis of IPSS intermediate-2 or high-risk MDS 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, treatment-naïve MDS subjects are allowed, and treatment-naïve 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] 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, or [3] pre-existing clinically significant dysfunction of the heart (LVEF <50%) or lung (DLCO or FEV1 <50% of expected) which is unrelated to the leukemia. |
| 2 | Men or women, 18 years of age or older |
| 3 | ECOG performance status of 0 to 2 |
| 4 | Total bilirubin < / = 2 x uln; SGOT and SGPT < / = 2.5 x uln |
| 5 | Creatinine < / = 1.5 x uln |
| 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 | Willing to comply with the protocol |
| 8 | Signed an approved study-specific informed consent and HIPAA |
| 1 | Major surgery within 4 weeks of first dose of SGI-110 |
| 2 | Chemotherapy within 2 weeks of first dose of SGI-110 (minimum of 6 weeks for nitrosoureas and 8 weeks for BMT with the exception of hydroxyurea which will be allowed for 7 days after first dose of SGI-110. |
| 3 | Refractory to prior decitabine treatment |
| 4 | Subjects with inaspirable bone marrow |
| 5 | Subjects with acute promyelocytic leukemia (M3 classification) |
| 6 | Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in-situ cervical cancer, or other cancer from which the subject has been disease-free for at least 5 years |
| 7 | Life-threatening illness other than MDS or AML, uncontrolled medical condition or organ system dysfunction which, in the investigator’s opinion, could compromise the subject’s safety, or put the study outcomes at risk |
| 8 | Uncontrolled or symptomatic arrhythmias or any NYHA Class 3 or 4 cardiac disease |
| 9 | Symptomatic CNS metastases or lesions for which treatment is required |
| 10 | Prior radiation therapy for extramedullary disease within 2 weeks of randomization |
| 11 | = / > Gr 2 toxicity (other than alopecia) continuing from prior anti-cancer therapy including radiation |
| 12 | Known history of HIV or active infection with hepatitis C virus (HCV) or hepatitis B virus (HBV) |
| 13 | Prior treatment with any investigational drug within 4 weeks of randomization |
| 14 | Being treated with systemic corticosteroids (other than for pre-medications or intermittent doses such as those used for allergic reactions and control of asthma) |
| 15 | Uncontrolled active systemic infections |
| 16 | Superimposed autoimmune hemolytic anemia or thrombocytopenia |
| 17 | Hypersensitivity to decitabine, SGI-110, or SGI-110 excipients |
| 18 | Uncontrolled CHF, CAD, COPD, or LVEF of < / = 50%, except for treatment-naïve elderly AML subjects |
| 19 | Pregnant or breastfeeding women. Women of childbearing potential must have a negative pregnancy test at screening and must be practicing two acceptable methods of birth control. Acceptable methods of birth control include IUD; oral, dermal (“patch”), implanted or injected contraceptives; tubal ligation; and barrier methods with spermicide. Women must also be willing to use 2 acceptable methods of contraception for 60 days after the last dose of study drug. Women of non-childbearing potential are those having hysterectomy; bilateral oophorectomy; or menopause defined as no menses for 1 year and 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. Men with female partners of childbearing potential should use effective contraception during this time. |
