Eltrombopag With Decitabine in Advanced Myelodysplastic Syndrome (MDS)
Condition: Leukemia
MeSH terms: Leukemia; Preleukemia; Myelodysplastic Syndromes; Syndrome
Intervention: Eltrombopag; Decitabine
Intervention description: Starting dose of Eltrombopag is 100 mg by mouth daily for each 28 day cycle. East Asians will start at 50 mg by mouth daily for each 28 day cycle.; Starting dose of Decitabine is 20 mg/m2 by vein on Days 1-5 for each 28 day cycle.
Intervention MeSH terms: Decitabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Leukemia; Advanced Myelodysplastic Syndrome; MDS; Intermediate-2 Myelodysplastic Syndrome; High-Risk Myelodysplastic Syndrome; Chronic myelomonocytic leukemia; CMML; Eltrombopag; Promacta; Decitabine; Dacogen

Summary:

      The goal of this clinical research study is to learn if eltrombopag given in combination with
      decitabine can help to control advanced MDS. The safety of this study drug combination will
      also be studied.
    

Eligibility criteria:

        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.