Eltrombopag With Decitabine in Advanced Myelodysplastic Syndrome (MDS)

Inclusion Criteria:

1. Signed, informed consent must be obtained prior to any study specific procedures.
2. Subjects with a histologically confirmed diagnosis of MDS by FAB criteria, including both MDS and RAEB-T (AML with 20-30% blasts and multilineage dysplasia) and chronic myelomonocytic leukemia (CMML) with at least 10% bone marrow blasts by World Health Organization (WHO) classification are eligible.
3. Advanced MDS by virtue of intermediate-2 or high-risk MDS by IPSS score, or high or very-high risk by IPSS-R.
4. Platelet count \</= 100 x 10\^9/L at baseline
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
6. Adequate liver function, as evidenced by a serum bilirubin \</= 2x the ULN (except for patients with a confirmed diagnosis of Gilbert's Disease) and an ALT or AST \</= 3x the laboratory ULN.
7. Serum creatinine \</= 2.5x upper limit of normal
8. Subjects must be \>/= 18 years of age at the time of informed consent
9. Subject is practicing an acceptable method of contraception (documented in chart). Female subjects (or female partners of male subject) must either be of non-childbearing potential (hysterectomy, bilateral oophorectomy, bilateral tubal ligation or post-menopausal \> 1 year), or of childbearing potential and use one of the following highly effective methods of contraception (i.e. Pearl index \< 1.0%) from 2 weeks prior to administration of study medication, throughout the study, and 28 days after completion or premature discontinuation from the study: - Complete abstinence from intercourse; - Intrauterine device (IUD); - Two forms of barrier contraception (diaphragm plus spermicide, and for males condom plus spermicide); - Male partner is sterile prior to entry into the study and is the only partner of the female; - Systemic contraceptives (combined or progesterone only).

Exclusion Criteria:

1. Subjects with any prior exposure to a thrombopoietin-receptor agonist
2. Prior hypomethylating agent treatment for MDS
3. Any prior or co-existing medical condition that in the investigator's judgment will substantially increase the risk associated with the subject's participation in the study
4. Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary study procedures
5. Active uncontrolled serious infection or sepsis at study enrollment
6. Clinically significant gastrointestinal disorders that may interfere with absorption of drug.
7. History of arterial thrombosis (i.e. stroke) in the past year
8. History of venous thrombosis currently requiring anti-coagulation therapy
9. Unstable angina, congestive heart failure (New York Heart Association (NYHA) \> Class II), uncontrolled hypertension (diastolic blood pressure \> 100mmHg), or recent (within 1 year) myocardial infarction
10. Subjects with a QTc \> 480 msec (QTc \> 510 msec for subjects with Bundle Branch Block) at baseline
11. Pregnant or breast-feeding
12. Subjects with known history of human immunodeficiency virus (HIV) or active infection with hepatitis C virus (HCV) or hepatitis B virus (HBV), because eltrombopag is hepatically cleared, and underlying hepatic impairment may lead to an increased risk of hepatotoxicity. Eltrombopag has not been evaluated with combination antiretroviral regimens.
13. Subjects with liver cirrhosis (as determined by the investigator)
14. Subjects with hypersensitivity to study drugs or their excipients.