Phase I Dose Finding/Phase II Placebo-Controlled Trial of Eltrombopag During Consolidation Therapy in Adults With Acute Myeloid Leukemia (AML) in Complete Remission

Inclusion Criteria:

• Cytomorphologically documented diagnosis of acute myeloid leukemia (AML). Acute
promyelocytic leukemia patients will be excluded (FAB M3). FAB classification and
cytogenetics must be noted at registration for each subject. For centers that do not use
FAB, a special review will be required.

Phase I Enrollment:

- Must be in first or second complete remission, e.g., no evidence of active disease in
blood, bone marrow (<5% blasts), or other tissues.

- For each remission, may have received no more than 2 cycles of induction treatment
(any type).

- May have received no more than one course of consolidation for the current remission
prior to enrollment (any type)

Phase II Enrollment:

- Must be in first complete remission, e.g., no evidence of active disease in blood,
bone marrow (<5% blasts), or other tissues.

- May have received no more than 2 cycles of induction treatment (any type).

Enrollment in Either Phase:

- Remission status must be documented by a bone marrow examination up to 14 days prior
to study registration.

- Have recovered from induction and first consolidation (if applicable) therapy side
effects (or ≤grade 1).

- ≥18 years of age and ≤65 years of age.

- ECOG performance status 0, 1, 2.

- Have not received cytotoxic drug therapy within 21 days of registration.

- Have not received hematopoietic colony stimulating growth factors within 14 days of
registration.

- Have not received packed red blood cells or platelets within 7 days of registration.

- Have not received investigational agents within 30 days of registration and will not
receive any investigational agents other than eltrombopag/placebo during study.

- Signed IRB-approved informed consent.

- Willing to provide blood samples for research purposes.

- Adequate organ function obtained within 28 days prior to registration:

- Absolute neutrophil count >1 x 10⁹/L

- Platelet count >100 x 10⁹/L

- Total direct serum bilirubin ≤1.5x upper limit of normal (ULN)

- ALT and AST ≤3x ULN

- BUN and serum creatinine <2x ULN

- Albumin ≥2.5 g/dL

- PT and PTT 80-120% of institutional normal range

- Women of childbearing potential must have a negative serum pregnancy test within 14
days of registration.

- Not pregnant nor breast feeding.

- Women of childbearing potential and sexually active males must use an accepted and
effective method of contraception.

- Patients of known East Asian ancestry (Chinese, Japanese, Taiwanese, and Korean) are
excluded from protocol participation for safety and efficacy reasons.

- Able to swallow and retain orally administered medication.

- No clinically significant gastrointestinal abnormalities such as malabsorption
syndrome or major resection of the stomach or bowels.

- No clinical evidence of hepatomegaly or splenomegaly.

- No known risk for Torsades de Pointes. (Eltrombopag use has not been shown to be
associated with Torsades de Pointes.)

- No active or unresolved infection and must be off all antibiotics for at least 7 days
prior to registration.

- No current evidence of invasive fungal infection.

- No known Hepatitis B, Hepatitis C active disease.

- No known Human Immunodeficiency Virus (HIV) seropositivity. The risk for potential
toxicities secondary to HIV (e.g., increased risk for fatal opportunistic infection)
may confound the toxicity profile of eltrombopag.

- Patients with a history of Central Nervous System (CNS) leukemia are eligible if
there is documentation of no current CNS involvement on cerebrospinal fluid (CSF)
examination (e.g., negative CSF by lumbar puncture) within 28 days of registration.

- No prior or concomitant malignancy in the past 5 years which is currently active and
likely to interfere with the patient's treatment for AML or which is likely to
increase the patient's morbidity or mortality. No prior chemotherapy or radiation
therapy allowed (unless related to AML treatment).

- No concurrent organ damage or medical problems that would prohibit therapy.