Eltrombopag With or Without Hypomethylating Agent After Hypomethylating Agent Failure For Patients With Myelodysplastic Syndrome (MDS)

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to 1 of 2
arms.The selection of treatment arm will be made by you and your treating physician.

- If you are in Arm A, you will receive eltrombopag alone.

- If you are in Arm B, you will receive eltrombopag and will continue to receive the
hypomethylating agent that you were receiving before you took part in this study.

Study Drug Administration:

You will take eltrombopag by mouth every day of each 28-day study cycle. If you are in Arm B,
you will also continue to take the hypomethylating agent you took before joining the study at
the same dosing schedule you were receiving before entering this study.

Eltrombopag should be taken on an empty stomach (1 hour before or 2 hours after a meal). Do
not eat calcium-rich foods (such as dairy products and calcium fortified juices), or take
other drugs (such as antacids) or supplements containing iron, calcium, aluminum, magnesium,
selenium, and/or zinc for 2 hours before or 4 hours after taking eltrombopag. If a dose of
eltrombopag is vomited, it should not be made up or re-taken on the same day. If the morning
dose is missed, it may be taken up until 5:00 PM on the same day.

Study Visits:

On Day 1 of all Cycles:

- You will have a physical exam including vital signs.

- Blood (about 2-3 teaspoons) will be drawn for routine tests.

On Days 8, 15, and 22 of Cycle 1:

- Your vital signs (blood pressure, heart rate, and temperature) will be measured.

- Blood (about 2-3 teaspoons) will be drawn for routine tests.

If the doctor thinks it is needed, on Day 1 of every 3 cycles (Cycles 3, 6, 9, and so on),
you will also have a bone marrow aspirate/biopsy to check the status of the disease and for
cytogenetic testing.

Length of Study:

You may continue taking the study drug(s) for as long as the doctor thinks it is in your best
interest. You will no longer be able to take the study drug(s) if the disease gets worse, if
intolerable side effects occur, or if you are unable to follow study directions.

Your participation on the study will be over after the follow-up visits.

End-of-Treatment Visit:

Within 5 days of your last dose of study drug, you will come to the clinic for an
end-of-treatment visit. The following procedures will be performed:

- You will have a physical exam.

- Blood (about 2-3 teaspoons) will be drawn for routine tests.

- You may have a bone marrow aspirate/biopsy collected to check the status of the disease
and for cytogenetic testing.

Follow-up Visit:

About 28 days after your last dose of study drug, you will come to the clinic for a follow-up
visit. the following procedures will be performed:

- You will have a physical exam.

- Blood (about 2-3 teaspoons) will be drawn for routine tests.

This is an investigational study. Eltrombopag is FDA approved and commercially available for
the treatment of low platelet counts in patients with idiopathic thrombocytopenic purpura
(ITP -- a severe bleeding disease). Its use in this study is investigational. Azacitidine and
decitabine are each FDA approved for the treatment of MDS and are commercially available. The
study doctor can explain how the study drug(s) are designed to work.

Up to 46 patients will take part in this study. All will be enrolled at MD Anderson.

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 IWG (platelet count < 100x10^9/L,
hemoglobin <11g/L or 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 IPSS

6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2

7. Adequate liver function, as evidenced by a serum bilirubin patients with a confirmed diagnosis of Gilbert's Disease) and an ALT or AST laboratory ULN.

8. Serum creatinine
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.