A multicenter phase II study of sepantronium bromide (YM155) plus rituximab in patients with relapsed aggressive B-cell Non-Hodgkin lymphoma

Abstract

This phase II study evaluated YM155, a novel small-molecule survivin suppressant, in combination with rituximab in patients with relapsed aggressive B-cell non-Hodgkin lymphoma (NHL) who failed or were not candidates for autologous stem cell transplant (ASCT). During 14-day cycles, 41 patients received YM155 (5mg/m²/d) by continuous intravenous (IV) infusion for 168 hours (day 1–7), and rituximab (375mg/m²) IV on days 1 and 8 during cycles 1–4 and repeated for 4 cycles every 10 cycles. Forty patients (97.6%) had prior rituximab and 15 patients (36.6%) prior ASCT. Most frequent grade 3–4 adverse events were neutropenia (19.5%) and thrombocytopenia (12.2%). In the per-protocol set (n = 34), objective response rate was 50% and median progression-free survival 17.9 months. Median overall survival was not reached at study termination (median follow-up, 23 months). YM155 in combination with rituximab was tolerable with encouraging antitumor activity and durable responses in relapsed aggressive B-cell NHL patients.

Keywords:

• YM155
• survivin
• non-Hodgkin lymphoma

Acknowledgements

Funding for this study was provided by Astellas Pharma. The authors thank the patients for their participation, and the investigators and their staff for their contributions to this study.

Potential conflict of interest

Kyriakos P. Papadopoulos served on an Astellas Advisory Board, and has received funding support for the conduct of clinical trial activities. Javier Lopez-Jimenez, Scott Smith, and Antoine Thyss have no conflicts of interest to declare. Joyce Steinberg, Anne Keating, Carolyn Sasse, and Fei Jie are employees of Astellas Pharma.

Funding was provided by Astellas Pharma for editorial assistance, which was provided by Anny Wu, PharmD, Craig Albright, PhD, and Brian Szente, PhD, from Complete Healthcare Communications, Inc. (Chadds Ford, PA).