Results of the randomized phase IIB ARCTIC trial of low-dose rituximab in previously untreated CLL.
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.
Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK.
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0000-0003-3333-9783
DR
Howard
Department of Haematology, St James's University Hospital, Leeds, UK.
T
T
Munir
Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK.
L
L
McParland
Haematological Malignancy Diagnostic Service, St James's University Hospital, Leeds, UK.
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0000-0003-0798-9790
AC
Rawstron
Centre for Haematology and Stem Cell Transplantation, Heartlands Hospital, Birmingham, UK.
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D
Milligan
Department of Oncology, University of Oxford and Department of Haematology, Oxford University Hospital Trust, Oxford, UK.
A
A
Schuh
Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK.
A
A
Hockaday
Department of Haematology, Hull and East Yorkshire NHS Trust, Hull, United Kingdom and Hull York Medical School, University of Hull, Hull, UK.
D J
0000-0001-6159-6109
DJ
Allsup
Department of Haematology, City Hospitals Sunderland, Sunderland, UK.
S
S
Marshall
Department of Haematology, University Hospital Southampton, Southampton, UK.
A S
AS
Duncombe
Academic Unit of Health Economics, Leeds Institute of Health Sciences, University of Leeds, Leeds, UK.
J L
JL
O'Dwyer
Academic Unit of Health Economics, Leeds Institute of Health Sciences, University of Leeds, Leeds, UK.
A F
AF
Smith
Academic Unit of Health Economics, Leeds Institute of Health Sciences, University of Leeds, Leeds, UK.
R
R
Longo
Department of Haematology, St James's University Hospital, Leeds, UK.
A
A
Varghese
Section of Experimental Haematology, Leeds Institute of Cancer and Pathology (LICAP), University of Leeds, Leeds, UK.
P
P
Hillmen
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D003365:Costs and Cost Analysis; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D000069283:Rituximab / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D016019:Survival Analysis
D000970:Antineoplastic Agents; D000069283:Rituximab