@article{8851bc0ff07b429a83a52a42cdb4dd44,
title = "Phase 1–2 study of vorinostat (SAHA), cladribine and rituximab (SCR) in relapsed B-cell non-Hodgkin lymphoma and previously untreated mantle cell lymphoma",
abstract = "Altered DNA methylation and histone acetylation in lymphoma provided the rationale for using vorinostat (SAHA), cladribine and rituximab (SCR) in non-Hodgkin lymphomas (NHL) in this phase 1–2 study (NCT00764517). Treatment included cladribine 5 mg/m2 intravenously (IV) (days 1–5), rituximab 375 mg/m2 IV (weekly 4× for cycle 1 and 1×/month) and vorinostat orally once daily (days 1–14) every 28 days for up to six cycles. Phase 1 included relapsed patients (n = 10) in a standard 3 + 3 dose escalation design (vorinostat: 200, 300 and 400 mg). No dose-limiting toxicities were seen. The phase 2 dose for vorinostat was 400 mg po (days 1–14). The majority of phase 2 patients had mantle cell lymphoma (MCL) (n = 57; 39 previously untreated, 10 relapsed). The primary objective was objective response rate [complete response (CR) + partial response] which was 39\% (7/18) in relapsed patients and 97\% (38/39) with 80\% (31/39) attaining a CR in previously untreated MCL. At a median follow-up of 42 months, median progression-free survival (PFS) and overall survival (OS) for relapsed NHL were 19·5 [95\% confidence interval (CI): 2·0–33·0] and 25·0 (95\% CI: 12·0–45·0) months respectively. Median PFS for previously untreated MCL was 84·0 months; OS could not be estimated. Toxicities were primarily haematological.",
author = "Spurgeon, \{Stephen E.\} and Kamal Sharma and Claxton, \{David F.\} and Christopher Ehmann and Jeffrey Pu and Sara Shimko and August Stewart and Nan Subbiah and Gundula Palmbach and Francis LeBlanc and Emile Latour and Chen, \{Yi Yi\} and Motomi Mori and Zainul Hasanali and Epner, \{Elliot M.\}",
note = "Funding Information: of subsequent amendments. Merck \& Co. employees were not involved in study design, data collection, analysis, or manuscript preparation or approval. Additional funding: S.E.S. Knight Cancer Institute Clinical Scholar Award and OHSU Tartar Trust Award. Funding Information: Funding This study was an investigator-initiated clinical trial sponsored by Merck \& Co. who provided vorinostat as well as funding support for correlative studies, start-up costs, nursing and physician time, and data coordination and management. The coordinating centre (Oregon Health \& Science University, OHSU) sub-contracted with the other participating centre (Penn State Hershey Cancer Institute, PSU). Cladribine and rituximab were used as standard of care agents and were not provided by the sponsor. Merck \& Co. approved the initial protocol and were provided with copies of subsequent amendments. Merck \& Co. employees were not involved in study design, data collection, analysis, or manuscript preparation or approval. Additional funding: S.E.S. Knight Cancer Institute Clinical Scholar Award and OHSU Tartar Trust Award. We thank the patients for their participation as well as the data management teams at Oregon Health \& Science University and Penn State Hershey Cancer Institute. Publisher Copyright: {\textcopyright} 2019 British Society for Haematology and John Wiley \& Sons Ltd",
year = "2019",
month = sep,
day = "1",
doi = "10.1111/bjh.16008",
language = "English (US)",
volume = "186",
pages = "845--854",
journal = "British Journal of Haematology",
issn = "0007-1048",
publisher = "John Wiley and Sons Inc.",
number = "6",
}