Title
A phase IIa study of Rituximab and Varlilumab in relapsed or refractory B-cell malignancies
Description
RiVa is a phase IIA clinical trial that evaluates the safety and efficacy of combining a direct tumour targeting antibody (rituximab) with a immunostimulatory antibody (varlilumab) for the treatment of patients with relapsed or treatment-refractory B-cell lymphoma.
Objectives
Primary Objectives:
- To document safety and tolerability of combined rituximab and varlilumab therapy.
- To document anti-tumour activity of combined rituximab and varlilumab therapy in relapsed or refractory B-cell
Secondary Objective:
- To measure the duration of response to rituximab and varlilumab over a follow-up period of 1 year.
Tertiary Objectives:
- To assess the level of B-cell depletion in the peripheral blood and, where relevant, tumour site following therapy.
- To establish the proportion of immune effector cell populations in the peripheral blood and, where relevant, tumour site following therapy.
- To assess whether the expression of CD27 is associated with response in combined rituximab and varlilumab therapy.
- To ascertain whether co-administration of rituximab and varlilumab alters their pharmacokinetic properties.
Trial Design
RiVa was a multicentre, randomised phase IIa trial in participants with relapsed or refractory CD20+B cell malignancies aiming to recruit 40 participants in total, with 20 participants in each of the following subcategories and 10 per treatment arm:
- Arm AÌý- High grade lymphoma (DLBCL, FL grade 3b, transformed FL) (n=20)
- Arm BÌý- Low grade lymphoma (e.g. FL grade 1, 2 or 3a, MZL, MCL, LPL) (n=20)
The trial included a safety run in where 6-12 participants were treated and the number of patients with dose limiting toxicities (DLTs) assessed. The trial would only progress to 40 participants if there were an acceptable number of DLTs in this safety run in.
Trial Status
Closed
Population
The study aimed to recurit 40 Patients aged ≥16 years with relapsed or refractory B-cell lymphoma.
Contact Details
All trial enquiries should be sent to ctuadmin@soton.ac.uk
Publications
Lim, S.H., Linton, K.M., Collins, G.P. 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 19, 619 (2018).Ìý
Sean H Lim, et al; Clinical and Biological Effects of Combined CD27 and CD20 Antibody Therapy in Relapsed/Refractory B-Cell Lymphoma: The Riva Trial. Blood 2021; 138 (Supplement 1): 715. doi:Ìý
Sean H Lim, et al; Clinical and Biological Effects of Combined CD27 and CD20 Antibody Therapy in Relapsed/Refractory B-Cell Lymphoma: The Riva Trial. Oral Presentation at the 63rd American Society of Haematology (ASH) Annual Meeting & Exposition, December 2021, Atlanta GA, USA
Lara Buermann, Louise Stanton, et al;ÌýCD27 Agonist Antibodies Mediate Clinical Responses through Intratumoral Stimulation in B-cell Malignancies: Multicenter RiVa Trial.ÌýClin Cancer Res. 2025 Nov 14;31(22)Ìýdoi: Ìý
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This trial was jointly funded by Cancer Research UK (award refence no. CRUKD/17/008) and Celldex Therapeutics.