Results of the randomized phase IIB ARCTIC trial of low-dose rituximab in previously untreated CLL

Howard, D. R.; Munir, T.; McParland, L.; Rawstron, A. C.; Milligan, D.; Schuh, A.; Hockaday, A.; Allsup, D. J.; Marshall, S.; Duncombe, A. S.; O'Dwyer, J. L.; Smith, A. F.; Longo, R.; Varghese, A.; Hillmen, P.

Abstract

© 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. ARCTIC was a multicenter, randomized-controlled, open, phase IIB non-inferiority trial in previously untreated chronic lymphocytic leukemia (CLL). Conventional frontline therapy in fit patients is fludarabine, cyclophosphamide and rituximab (FCR). The trial hypothesized that including mitoxantrone with low-dose rituximab (FCM-miniR) would be non-inferior to FCR. A total of 200 patients were recruited to assess the primary end point of complete remission (CR) rates according to IWCLL criteria. Secondary end points were progression-free survival (PFS), overall survival (OS), overall response rate, minimal residual disease (MRD) negativity, safety and cost-effectiveness. The trial closed following a pre-planned interim analysis. At final analysis, CR rates were 76 FCR vs 55% FCM-miniR (adjusted odds ratio: 0.37; 95% confidence interval: 0.19-0.73). MRD-negativity rates were 54 FCR vs 44% FCM-miniR. More participants experienced serious adverse reactions with FCM-miniR (49%) compared to FCR (41%). There are no significant differences between the treatment groups for PFS and OS. FCM-miniR is not expected to be cost-effective over a lifetime horizon. In summary, FCM-miniR is less well tolerated than FCR with an inferior response and MRD-negativity rate and increased toxicity, and will not be taken forward into a confirmatory trial. The trial demonstrated that oral FCR yields high response rates compared to historical series with intravenous chemotherapy.

Citation

Howard, D. R., Munir, T., McParland, L., Rawstron, A. C., Milligan, D., Schuh, A., Hockaday, A., Allsup, D. J., Marshall, S., Duncombe, A. S., O'Dwyer, J. L., Smith, A. F., Longo, R., Varghese, A., & Hillmen, P. (2017). Results of the randomized phase IIB ARCTIC trial of low-dose rituximab in previously untreated CLL. Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K, 31(11), 2416-2425. https://doi.org/10.1038/leu.2017.96

• Journal Article Type: Article
• Acceptance Date: Mar 8, 2017
• Online Publication Date: May 2, 2017
• Publication Date: Nov 1, 2017
• Deposit Date: Mar 22, 2018
• Publicly Available Date: Apr 16, 2018
• Journal: Leukemia
• Print ISSN: 0887-6924
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 31
• Issue: 11
• Pages: 2416-2425
• DOI: https://doi.org/10.1038/leu.2017.96
• Keywords: Anesthesiology and Pain Medicine; Cancer Research; Hematology
• Public URL: https://hull-repository.worktribe.com/output/746715
• Publisher URL: https://www.nature.com/articles/leu201796
• Related Public URLs: http://eprints.whiterose.ac.uk/115664/
• Contract Date: Apr 16, 2018