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...
Main Authors: | , , , , , , , , , , , , , , |
---|---|
Format: | Article in Journal/Newspaper |
Language: | English |
Published: |
Nature Publishing Group
2017
|
Subjects: | |
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 |
id |
ftleedsuniv:oai:eprints.whiterose.ac.uk:115664 |
---|---|
record_format |
openpolar |
spelling |
ftleedsuniv:oai:eprints.whiterose.ac.uk:115664 2023-05-15T14:26:38+02:00 Results of the randomized phase IIB ARCTIC trial of low dose Rituximab in previously untreated CLL 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 2017-05-02 text 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 en eng Nature Publishing Group https://eprints.whiterose.ac.uk/115664/1/Results%20of%20the%20randomized%20phase%20IIB%20ARCTIC%20trial%20of%20low%20dose%20Rituximab%20in%20previously%20untreated%20CLL.pdf Howard, DR orcid.org/0000-0003-3333-9783 , Munir, T, McParland, L et al. (12 more authors) (2017) Results of the randomized phase IIB ARCTIC trial of low dose Rituximab in previously untreated CLL. Leukemia, 31. pp. 2416-2425. ISSN 0887-6924 Article NonPeerReviewed 2017 ftleedsuniv 2023-01-30T21:54:19Z 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. Article in Journal/Newspaper Arctic Arctic White Rose Research Online (Universities of Leeds, Sheffield & York) Arctic |
institution |
Open Polar |
collection |
White Rose Research Online (Universities of Leeds, Sheffield & York) |
op_collection_id |
ftleedsuniv |
language |
English |
description |
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. |
format |
Article in Journal/Newspaper |
author |
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 |
spellingShingle |
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 Results of the randomized phase IIB ARCTIC trial of low dose Rituximab in previously untreated CLL |
author_facet |
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 |
author_sort |
Howard, DR |
title |
Results of the randomized phase IIB ARCTIC trial of low dose Rituximab in previously untreated CLL |
title_short |
Results of the randomized phase IIB ARCTIC trial of low dose Rituximab in previously untreated CLL |
title_full |
Results of the randomized phase IIB ARCTIC trial of low dose Rituximab in previously untreated CLL |
title_fullStr |
Results of the randomized phase IIB ARCTIC trial of low dose Rituximab in previously untreated CLL |
title_full_unstemmed |
Results of the randomized phase IIB ARCTIC trial of low dose Rituximab in previously untreated CLL |
title_sort |
results of the randomized phase iib arctic trial of low dose rituximab in previously untreated cll |
publisher |
Nature Publishing Group |
publishDate |
2017 |
url |
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 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic Arctic |
genre_facet |
Arctic Arctic |
op_relation |
https://eprints.whiterose.ac.uk/115664/1/Results%20of%20the%20randomized%20phase%20IIB%20ARCTIC%20trial%20of%20low%20dose%20Rituximab%20in%20previously%20untreated%20CLL.pdf Howard, DR orcid.org/0000-0003-3333-9783 , Munir, T, McParland, L et al. (12 more authors) (2017) Results of the randomized phase IIB ARCTIC trial of low dose Rituximab in previously untreated CLL. Leukemia, 31. pp. 2416-2425. ISSN 0887-6924 |
_version_ |
1766299906847277056 |