A Phase 2 Trial of MLN8237, an Oral Aurora A Kinase Inhibitor, in Adult Patients With Aggressive Non-Hodgkin's Lymphoma

Inclusion Criteria

Each patient must meet all of the following inclusion criteria to be enrolled in the
study:

1. Patients must have histological or cytological diagnosis of a hematological
malignancy of the following types that has relapsed or was refractory to prior
therapy:

- Diffuse large B-cell lymphoma

- Mantle cell lymphoma

- Burkitt's lymphoma

- Precursor B-lymphoblastic leukemia/lymphoma

- T-cell lymphoma, excluding primary cutaneous T-cell lymphoma

- Transformed follicular lymphoma with ≥ 50% diffuse large cell component

2. Male or female patients 18 years or older

3. Eastern Cooperative Oncology Group (ECOG) performance status 0-2

4. Measurable disease

Exclusion criteria include the following:

1. Pregnant or lactating females

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

3. Any serious medical or psychiatric illness that could interfere with the completion
of treatment

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 up to 5 times the ULN if their elevation can be reasonably
ascribed to their underlying hematological disorder.

6. Absolute neutrophil count (ANC) < 1,250/mm3

7. Platelet count < 75,000/mm3

8. Calculated creatinine clearance < 30 mL/minute

9. Autologous stem cell transplant less than 6 months prior to enrollment

10. Patients who have undergone allogeneic stem cell or organ transplantation

11. Systemic antineoplastic therapy within 14 days preceding the first dose of study drug
treatment

12. Patients who have received treatment with nitrosoureas, mitomycin C, rituximab,
alemtuzumab, or other unconjugated antibody treatment, within 42 days

13. Patients who have received treatment with radioimmunoconjugates or within 12 weeks

14. Patients who have received radiotherapy within 21 days prior to first dose

15. 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

16. Major surgery within 14 days prior to the first dose

17. Infection requiring systemic antibiotic therapy within 14 days prior to the first
dose or other serious infection

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

19. Inability to swallow capsules

20. History of uncontrolled sleep apnea syndrome and other conditions that could result
in excessive daytime sleepiness.