title: 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/m(2)/d) by continuous intravenous (IV) infusion for 168 hours (day 1-7), and rituximab (375mg/m(2)) 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.
authors: a South Texas Accelerated Research Therapeutics , San Antonio , TX , USA ;
authors: Kyriakos P
authors: KP
authors: Papadopoulos
authors: b Hospital Universitario Ramon y Cajal , Madrid , Spain ;
authors: Javier
authors: J
authors: Lopez-Jimenez
authors: c Loyola University Hospital , Maywood , IL , USA ;
authors: Scott E
authors: SE
authors: Smith
authors: d Astellas Pharma , Northbrook , IL , USA ;
authors: Joyce
authors: J
authors: Steinberg
authors: d Astellas Pharma , Northbrook , IL , USA ;
authors: Anne
authors: A
authors: Keating
authors: d Astellas Pharma , Northbrook , IL , USA ;
authors: Carolyn
authors: C
authors: Sasse
authors: d Astellas Pharma , Northbrook , IL , USA ;
authors: Fei
authors: F
authors: Jie
authors: e Center Antoine Lacassagne , Nice , France.
authors: Antoine
authors: A
authors: Thyss
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D064146:Chemotherapy-Induced Febrile Neutropenia / Q000453:epidemiology; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors*; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009285:Naphthoquinones / Q000627:therapeutic use*; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D000069283:Rituximab / Q000627:therapeutic use*; D000077022:Survivin; D013921:Thrombocytopenia / Q000139:chemically induced / Q000453:epidemiology; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D007093:Imidazoles; D051034:Inhibitor of Apoptosis Proteins; D009285:Naphthoquinones; D000077022:Survivin; D000069283:Rituximab; C523798:sepantronium
keywords: YM155; non-Hodgkin lymphoma; survivin