A Phase 2 Trial of MLN8237, an Oral Aurora A Kinase Inhibitor, in Adult Patients With Acute Myelogenous Leukemia and High-Grade Myelodysplastic Syndrome

Inclusion Criteria:

Each patient must meet all of the following inclusion criteria:

1. Male or female patients 18 years or older

2. Eligible diagnoses:

- Acute myelogenous leukemia (except APL) with > 10% bone marrow or peripheral
blood blasts; failed to achieve CR or relapse after prior therapy, not
candidates for potentially curative treatment. Untreated patients > 60 are
eligible if not candidates for standard induction.

- High-grade MDS, defined by all the following features: IPSS Intermediate-2 or
High Risk; > 10% blasts on bone marrow examination; treatment failure from, or
not candidates for, standard therapies including demethylating agents, eg
azacytidine or decitabine.

3. Eastern Cooperative Oncology Group perf. status 0-2

4. Female patients:

- Postmenopausal for at least one year

- Surgically sterile, or

- If childbearing potential, agree to practice two effective methods of
contraception or abstain from heterosexual intercourse.

5. Male patients:

- Practice effective barrier contraception to one month after the last dose of
study drug, or

- Abstain from heterosexual intercourse.

6. Voluntary written consent

7. Patients on hydroxyurea may be included

Exclusion Criteria:

1. Pregnant or lactating females

2. Known human immunodeficiency virus (HIV) positive or AIDS-related illness

3. Serious medical or psychiatric illness that could, in the investigator's opinion,
potentially interfere with the protocol completion

4. Total bilirubin > 1.5 × the upper limit of normal (ULN)

5. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) > 2.5 × the ULN.
AST, ALT may be elevated to 5 x the ULN if reasonably ascribed to underlying
hematological disorder.

6. Calculated creatinine clearance < 30 mL/minute

7. Antineoplastic or radiotherapy within 14 days preceding the first dose

8. Myocardial infarction within 6 months of enrollment or current history of New York
Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe
uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute
ischemia

9. Major surgery 14 days prior to the first dose

10. Clinically uncontrolled central nervous system (CNS) involvement.

11. Inability to swallow capsules

12. History of uncontrolled sleep apnea or conditions that result in excessive daytime
sleepiness, such as chronic lung disease