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

ARCTIC was a multi-center, 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...

Full description

Bibliographic Details
Main Authors: Howard, DR, Munir, T, McParland, L, Rawstron, AC, Milligan, D, Schuh, A, Hockaday, A, Allsup, DJ, Marshall, S, Duncombe, AS, O’Dwyer, JL, Smith, AF, Longo, R, Varghese, A, Hillmen, P
Format: Article in Journal/Newspaper
Language:English
Published: Nature Publishing Group 2017
Subjects:
Arctic
Online Access:https://eprints.whiterose.ac.uk/115664/
https://eprints.whiterose.ac.uk/115664/1/Results%20of%20the%20randomized%20phase%20IIB%20ARCTIC%20trial%20of%20low%20dose%20Rituximab%20in%20previously%20untreated%20CLL.pdf
Description
Summary:ARCTIC was a multi-center, 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. 200 patients were recruited to assess the primary endpoint of complete remission (CR) rates according to IWCLL criteria. Secondary endpoints were progression-free survival (PFS), overall survival (OS), overall response rate, minimal residual disease (MRD) negativity, safety and cost-effectiveness. The trial closed following the pre-planned interim analysis. At final analysis, CR rates were 76% FCR vs 55% FCM-miniR [adjusted odds-ratio: 0.37; 95% CI: 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.

Similar Items