PURPOSE: Aurora A kinase (AAK) is overexpressed in aggressive lymphomas and can 
correlate with more histologically aggressive forms of disease. We therefore 
designed a phase II study of alisertib, a selective AAK inhibitor, in patients 
with relapsed and refractory aggressive non-Hodgkin lymphomas.
PATIENTS AND METHODS: Patients age ≥ 18 years were eligible if they had relapsed 
or refractory diffuse large B-cell lymphoma (DLBCL), mantle-cell lymphoma (MCL), 
transformed follicular lymphoma, Burkitt's lymphoma, or noncutaneous T-cell 
lymphoma. Alisertib was administered orally at 50 mg twice daily for 7 days in 
21-day cycles.
RESULTS: We enrolled 48 patients. Histologies included DLBCL (n = 21), MCL (n = 
13), peripheral T-cell lymphoma (n = 8), transformed follicular lymphoma (n = 
5), and Burkitt's (n = 1). Most common grade 3 to 4 adverse events were 
neutropenia (63%), leukopenia (54%), anemia (35%), thrombocytopenia (33%), 
stomatitis (15%), febrile neutropenia (13%), and fatigue (6%). Four deaths 
during the study were attributed to progressive non-Hodgkin lymphoma (n = 2), 
treatment-related sepsis (n = 1), and unknown cause (n = 1). The overall 
response rate was 27%, including responses in three of 21 patients with DLBCL, 
three of 13 with MCL, one of one with Burkitt's lymphoma, two of five with 
transformed follicular lymphoma, and four of eight with noncutaneous T-cell 
lymphoma. The alisertib steady-state trough concentration (n = 25) revealed the 
expected pharmacokinetic variability, with a trend for higher incidence of 
adverse event-related dose reductions at higher trough concentrations. Analysis 
for AAK gene amplification and total AAK protein revealed no differences between 
histologies or correlation with clinical response.
CONCLUSION: The novel AAK inhibitor alisertib seems clinically active in both B- 
and T-cell aggressive lymphomas. On the basis of these results, confirmatory 
single-agent and combination studies have been initiated.