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

• Published in: Leukemia Vol. 31; no. 11; pp. 2416 - 2425
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-11-2017; Nature Publishing Group
• Subjects: 631/67/1990/283/1895; 692/308/2779/109/1941; 692/308/2779/777; 692/700/1750; 692/700/565/1436/99; Adult; Aged; Aged, 80 and over; Analysis; Antineoplastic Agents - adverse effects; Antineoplastic Agents - economics; Antineoplastic Agents - therapeutic use; Cancer Research; Chemotherapy; Chronic lymphocytic leukemia; Clinical trials; Confidence intervals; Cost analysis; Costs and Cost Analysis; Critical Care Medicine; Cyclophosphamide; Diseases; Dosage and administration; Dose-Response Relationship, Drug; Drug therapy; Female; Fludarabine; Hematology; Humans; Immunotherapy; Intensive; Internal Medicine; Intravenous administration; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy; Lymphatic leukemia; Lymphocytic leukemia; Male; Medicine; Medicine & Public Health; Middle Aged; Minimal residual disease; Mitoxantrone; Monoclonal antibodies; Oncology; original-article; Patients; Pharmaceutical industry; Polar environments; Product development; Public relations executives; Randomization; Remission; Rituximab; Rituximab - adverse effects; Rituximab - economics; Rituximab - therapeutic use; Survival; Survival Analysis; Targeted cancer therapy; Toxicity; Treatment outcome; Arctic; United Kingdom
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/leu.2017.96

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.