Abstract
TPS8109 Background: DLBCL and TFL are aggressive subtypes of non-Hodgkin lymphoma (NHL), with poor prognosis in the rel/ref setting. Alternatives to standard rituximab-based treatments are needed. MLN8237 is an oral, selective inhibitor of Aurora A kinase – a key mitotic regulator overexpressed/amplified in various human cancers, including lymphomas (Hamada et al, 2003; Yakushijin et al, 2004; Qi et al, 2011). Emerging data from a phase 2 study suggest that MLN8237 has single agent activity in aggressive NHL (Friedberg et al, ASH 2011). MLN8237 + rituximab (MR) ± vincristine (MRV) has also shown activity in preclinical B-cell NHL models (Mahadevan et al, ASH 2011). Further clinical evaluation of these regimens in rel/ref B-cell NHL is warranted. Methods: This single-arm phase 1/2 study (ClinicalTrials.gov #NCT01397825) aims to assess the safety, efficacy, and pharmacokinetics of, and determine a recommended phase 2 dose (RP2D) and schedule for, MR and MRV in adults with CD20+ rel/ref DLBCL/TFL after 1–4 prior regimens (including ASCT) and ECOG PS 0–2. Pts with other aggressive B-cell lymphomas may also enroll in phase 1. ~100 pts will be recruited at 22 sites in the US, UK, Italy, and Spain, and study duration will be ~2 years. In part 1, a safety lead-in cohort will receive MR (table), with the RP2D determined as when <2 dose limiting toxicities (DLT) occur in 6 pts in cycle 1. MRV dose escalation (part 2) will then follow a 3+3 design. Phase 2 enrollment (part 3) will follow a Simon optimal 2-stage design, with pts receiving MRV at the RP2D determined in part 2. The primary phase 2 objective is overall response rate by IWG criteria. Responders may continue MLN8237 if clinical benefit is seen and if the regimen is tolerable. Enrollment as of 20 Jan 2012 is 6 evaluable pts. [Table: see text]
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