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Published in: Trials 1/2018

Open Access 01-12-2018 | Study protocol

RIVA – a phase IIa study of rituximab and varlilumab in relapsed or refractory B-cell malignancies: study protocol for a randomized controlled trial

Authors: Sean H. Lim, Kim M. Linton, Graham P. Collins, Joke Dhondt, Joshua Caddy, Liz Rossiter, Karan Vadher, Keira Fines, Laura E. Rogers, Diana Fernando, Louise Stanton, Andrew J. Davies, Peter W. M. Johnson, Gareth Griffiths

Published in: Trials | Issue 1/2018

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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.
Appendix
Available only for authorised users
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Metadata
Title
RIVA – a phase IIa study of rituximab and varlilumab in relapsed or refractory B-cell malignancies: study protocol for a randomized controlled trial
Authors
Sean H. Lim
Kim M. Linton
Graham P. Collins
Joke Dhondt
Joshua Caddy
Liz Rossiter
Karan Vadher
Keira Fines
Laura E. Rogers
Diana Fernando
Louise Stanton
Andrew J. Davies
Peter W. M. Johnson
Gareth Griffiths
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Trials / Issue 1/2018
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-018-2996-6

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