RIVA - a phase IIa study of rituximab and varlilumab in relapsed or refractory B-cell malignancies: study protocol for a randomized controlled trial.
dc.contributor.author | Lim, SH | |
dc.contributor.author | Linton, Kim M | |
dc.contributor.author | Collins, GP | |
dc.contributor.author | Dhondt, J | |
dc.contributor.author | Caddy, J | |
dc.contributor.author | Rossiter, L | |
dc.contributor.author | Vadher, K | |
dc.contributor.author | Fines, K | |
dc.contributor.author | Rogers, LE | |
dc.contributor.author | Fernando, D | |
dc.contributor.author | Stanton, L | |
dc.contributor.author | Davies, AJ | |
dc.contributor.author | Johnson, PWM | |
dc.contributor.author | Griffiths, G | |
dc.date.accessioned | 2018-12-10T11:48:55Z | |
dc.date.available | 2018-12-10T11:48:55Z | |
dc.date.issued | 2018 | en |
dc.identifier.citation | Lim SH, Linton KM, Collins GP, Dhondt J, Caddy J, Rossiter L, et al. RIVA - a phase IIa study of rituximab and varlilumab in relapsed or refractory B-cell malignancies: study protocol for a randomized controlled trial. Trials. 2018 Nov 9;19(1):619. | en |
dc.identifier.pmid | 30413184 | en |
dc.identifier.doi | 10.1186/s13063-018-2996-6 | en |
dc.identifier.uri | http://hdl.handle.net/10541/621412 | |
dc.description.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. | en |
dc.language.iso | en | en |
dc.relation.url | https://dx.doi.org/10.1186/s13063-018-2996-6 | en |
dc.title | RIVA - a phase IIa study of rituximab and varlilumab in relapsed or refractory B-cell malignancies: study protocol for a randomized controlled trial. | en |
dc.type | Article | en |
dc.contributor.department | Antibody and Vaccine Group, Centre for Cancer Immunology, University of Southampton, Southampton, UK | en |
dc.identifier.journal | Trials | en |