Abstract

Background

Over 12,000 new cases of B-cell malignancies are diagnosed in the UK each year, with diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) being the most common subtypes. Standard frontline therapy consists of immunochemotherapy with a CD20 monoclonal antibody (mAb), such as rituximab, delivered in combination with multi-agent chemotherapy. Despite being considered a treatable and potentially curable cancer, approximately 30% of DLBCL cases will relapse after frontline therapy. Advanced stage FL is incurable and typically has a relapsing and remitting course with a frequent need for re-treatment. Based on supportive preclinical data, we hypothesised that the addition of varlilumab (an anti-CD27 mAb) to rituximab (an anti-CD20 mAb) can improve the rate, depth and duration of the response of rituximab monotherapy in patients with relapsed or refractory B-cell malignancies.

Methods/design

Combination treatment of varlilumab plus rituximab, in two different dosing regimens, is being tested in the RIVA trial. RIVA is a two-stage open-label randomised phase IIa design in up to 40 patients with low- or high-grade relapsed or refractory CD20+ B-cell lymphoma. The study is open to recruitment in the UK. Enrolled patients are randomised 1:1 to two different experimental varlilumab to rituximab combinations.

The primary objective is to determine the safety and tolerability of the combination and the anti-tumour activity (response) in relapsed or refractory B-cell malignancies. Secondary objectives will include an evaluation of the duration of the response and overall survival. Tertiary translational objectives include assessment of B-cell depletion, changes in immune effector cell populations, expression of CD27 as a biomarker of response and pharmacokinetic properties. Analyses will not be powered for formal statistical comparisons between treatment arms.

Discussion

RIVA will determine whether the combination of rituximab and varlilumab in relapsed or refractory B-cell malignancies is active and safe prior to future phase II/III trials.

Trial registration

EudraCT, 2017–000302-37. Registered on 16 January 2017. ISRCTN, ISRCTN15025004. Registered on 16 August 2017.

Details

Title
RIVA – a phase IIa study of rituximab and varlilumab in relapsed or refractory B-cell malignancies: study protocol for a randomized controlled trial
Author
Lim, Sean H. 1 ; Linton, Kim M. 2 ; Collins, Graham P. 3 ; Dhondt, Joke 4   VIAFID ORCID Logo  ; Caddy, Joshua 4 ; Rossiter, Liz 4 ; Vadher, Karan 4 ; Fines, Keira 4 ; Rogers, Laura E. 4 ; Fernando, Diana 4 ; Stanton, Louise 4 ; Davies, Andrew J. 5 ; Johnson, Peter W. M. 6 ; Griffiths, Gareth 4 

1  University of Southampton, Antibody and Vaccine Group, Centre for Cancer Immunology, Southampton, UK (GRID:grid.5491.9) (ISNI:0000 0004 1936 9297) 
2  University of Manchester, Manchester Cancer Research Centre, Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, Southampton, UK (GRID:grid.5379.8) (ISNI:0000000121662407) 
3  Oxford University Hospitals NHS Foundation Trust, Department of Haematology, Oxford, UK (GRID:grid.410556.3) (ISNI:0000 0001 0440 1440) 
4  University of Southampton, Southampton Clinical Trials Unit, Centre for Cancer Immunology, Southampton, UK (GRID:grid.5491.9) (ISNI:0000 0004 1936 9297) 
5  University of Southampton, ECMC Southampton, Southampton, UK (GRID:grid.5491.9) (ISNI:0000 0004 1936 9297) 
6  University of Southampton, CRUK Centre Southampton, Southampton, UK (GRID:grid.5491.9) (ISNI:0000 0004 1936 9297) 
Pages
619
Publication year
2018
Publication date
Dec 2018
Publisher
Springer Nature B.V.
e-ISSN
17456215
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1186/s13063-018-2996-6
ProQuest document ID
2795264514
Copyright
© The Author(s). 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.