Eltrombopag With or Without Hypomethylating Agent After Hypomethylating Agent Failure For Patients With Myelodysplastic Syndrome (MDS)
Condition: Leukemia
MeSH terms: Preleukemia; Myelodysplastic Syndromes
Intervention: Eltrombopag; Hypomethylating Agent (HMA)
Intervention description: 200 mg by mouth daily in a 28 day cycle.; The choice of HMA agent (e.g. azacitidine or decitabine) will be the HMA the patient has received prior to enrollment on study.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 29.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Leukemia; Myelodysplastic syndrome; MDS; Overall response rate; ORR; Eltrombopag; Promacta; Hypomethylating Agent

Summary:

      The goal of this clinical research study is to learn if eltrombopag can help to control MDS.
      The safety of this drug 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) by World
             Health Organization (WHO) classification are eligible.

          3. Patients must have completed at least 4 cycles of hypomethylating agent therapy (e.g
             azacitidine or decitabine) with failure to achieve at least a partial response, or
             with the presence of ongoing cytopenias per International Working Group (IWG)
             (platelet count < 100x10^9/L, hemoglobin <11g/L or Absolute Neutrophil Count (ANC)
             <1x10^9/L). Patients with progressive disease on HMA-therapy prior to this time point
             are also eligible at the time of documented progression. Therapy with decitabine
             analogs (i.e. SGI-110) will be considered as decitabine for the purposes of this
             study.

          4. Platelet count <100x10^9/L

          5. Low, intermediate-1, intermediate-2 or High-risk category by International Prognostic
             Scoring System (IPSS)

          6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2

          7. 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 Alanine
             Aminotransferase (ALT) or Aspartate Aminotransferase (AST) </=3x the laboratory Upper
             Limit of Normal (ULN).

          8. Serum creatinine </=2x upper limit of normal

          9. Subjects must be>/= 18 years of age at the time of informed consent, because no dosing
             or adverse event data are currently available on the use of eltrombopag in children.

         10. 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).

         11. Patients must have recovered from acute toxicity (to grade 1 or less) of all previous
             therapy prior to enrollment. Treatment may start earlier if necessitated by the
             patient's medical condition (e.g. progressive disease) following discussion with the
             Investigator.

        Exclusion Criteria:

          1. Subjects with any prior exposure to a thrombopoietin-receptor agonist

          2. 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

          3. Psychiatric disorders or altered mental status precluding understanding of the
             informed consent process and/or completion of the necessary study procedures

          4. Active uncontrolled serious infection or sepsis at study enrollment

          5. Clinically significant gastrointestinal disorders that may interfere with absorption
             of drug.

          6. History of arterial thrombosis (i.e. stroke) in the past year

          7. History of venous thrombosis currently requiring anti-coagulation therapy

          8. 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

          9. Subjects with a QTc > 480 msec (QTc > 510 msec for subjects with Bundle Branch Block)
             at baseline

         10. Pregnant or breast-feeding because there are no adequate and well-controlled studies
             of eltrombopag use in pregnancy and it is unknown whether eltrombopag is excreted in
             human milk.

         11. 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.