Eltrombopag in Elderly Acute Myelogenous Leukemia (AML)

Primary Objectives (Phase I Portion): 1). To determine the safety and tolerability of
eltrombopag in elderly subjects with AML 2). To determine the maximally tolerated initial
starting dose of eltrombopag for elderly subjects with AML Primary Objectives (Phase II
portion): 1). To better define the safety and tolerability of eltrombopag in elderly patients
with AML at the maximally tolerated starting dose Page 9 of 18 determined in Phase I portion
of study. 2). To determine the incidence of peripheral platelet count improvement (using
baseline and response parameters as defined below) for subjects with disease related
thrombocytopenia. Secondary Objectives (Phase I and II): 1). To preliminarily determine the
efficacy (using AML response criteria as defined below) of eltrombopag in elderly subjects
with AML.

2). To perform ex-vivo analyses using subject AML samples and stock eltrombopag to 1) assess
leukemic proliferative capacity and 2) investigate potential eltrombopag induced cytoxic
mechanisms for leukemic cell death. 3). To perform pharmacodynamic assessments of drug
activity in leukemic cells using subject samples collected at various time points before and
during drug exposure. 4). To preliminarily correlate pharmacodynamic findings with clinical
response.

Inclusion Criteria:

- A diagnosis of non-M3 AML which is either: a). Relapsed after standard chemotherapy or
transplant;

- Newly diagnosed in a patient who is not an appropriate or willing candidate for
standard induction chemotherapy - Age equal to or greater than 60 - Platelet count
less than 75 - ECOG performance status of 0-2

- Life expectancy of at least 4 weeks

- Must be able to consume oral medication

- Must have recovered from toxic effects of prior chemotherapy

- Patients must be able to sign consent and be willing and able to comply with scheduled
visits, treatment plan and laboratory testing.

- For Phase I portion only: Subject must be of non-East Asian (Japanese, Chinese,
Taiwanese or Korean) descent.

- For Phase II portion subject can be either East Asian or non-East Asian descent.

Exclusion Criteria:

- Cytotoxic chemotherapy (including azacitadine or decitabine) within the past 28 days
other than hydroxyurea

- Active participation in any other investigational treatment study for AML.

- Known HIV or Hepatitis C

- ECOG performance status greater than 2

- Uncontrolled intercurrent illness including, but not limited to: uncontrolled ongoing
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.

- Previous therapy with romiplostim or any other TPO-R agonist