Abstract
TPS8110 Background: PTCL is a rare form of aggressive non-Hodgkin lymphoma (NHL), accounting for 5–20% of NHL diagnoses. Standard NHL therapies developed primarily for B-cell lymphomas are not optimal for PTCL and early relapse is common. Current treatments for rel/ref PTCL include pralatrexate, romidepsin, and gemcitabine; however, outcomes remain poor. The oral, investigational drug, MLN8237, is a selective inhibitor of Aurora A kinase (AAK) – a key mitotic regulator that is overexpressed or amplified in various human tumors. Emerging clinical data from a phase II study of single agent MLN8237 in rel/ref aggressive T-cell lymphoma (Friedberg et al, ASH 2011) support further clinical evaluation in this indication. Methods: In this open-label, randomized, phase III study, a maximum of 354 adults with rel/ref PTCL after ≥1 prior systemic cytotoxic therapies will be enrolled at approximately 140 centers worldwide. Pts will be randomized 1:1 to MLN8237 50 mg twice daily as an enteric coated tablet on days 1–7 of 21-day cycles, or to investigator’s choice of: pralatrexate 30 mg/m2 IV once weekly for 6 weeks in 7-week cycles; romidepsin 14 mg/m2 IV on days 1, 8, and 15 of 28-day cycles; or gemcitabine 1000 mg/m2 IV on days 1, 8, and 15 of 28-day cycles. Pts with disease response/stabilization will be able to continue treatment provided that clinical benefit is demonstrated and treatment is tolerable. The expected study duration is 44 months. Primary endpoints are overall response rate (complete response [CR] + partial response) and progression free survival by International Working Group criteria (Cheson et al, 2007). Secondary endpoints include CR rate, overall survival, time to progression, time to response, duration of response, safety, and quality of life. Exploratory endpoints include an evaluation of candidate biomarkers (such as AAK protein expression levels and gene amplification, and the tumor proliferative marker Ki-67) in tumor biopsies. This study is registered at ClinicalTrials.gov: #NCT01482962.
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