Inclusion Criteria:

• Cytomorphologically documented diagnosis of acute myeloid leukemia (AML). Acute promyelocytic leukemia patients will be excluded (FAB M3). FAB classification, cytogenetics and molecular markers (if applicable) must be available at registration.

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 28 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 ≤70 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.