A global study of novel agents in paediatric and adolescent relapsed and refractory B-cell non-Hodgkin lymphoma (Glo-BNHL): protocol for an adaptive international platform clinical trial

Abstract

The second Paediatric Strategy Forum of the international multi-stakeholder organisation, ACCELERATE (Nov-2017), concluded that an international approach to conducting clinical trials in relapsed and refractory paediatric B-cell non-Hodgkin lymphoma (r/r B-NHL) was critical and that robust prioritisation of novel targeted agents was essential to ensure only those showing maximum potential move forward for investigation. Glo-BNHL is a multi-arm, non-randomised, open-label, international, platform clinical trial to assess safety and efficacy of prioritised novel agents for the treatment of r/r B-NHL. The ACCELERATE Forum identified three classes of agents for immediate prioritisation within the platform: 1. Bispecific antibodies (BsAbs); 2. Antibody–drug conjugates (ADCs) combined with standard chemotherapy; and 3. Chimeric antigen receptor (CAR) T-cells. Promising and available novel agents from each class will be evaluated as parallel treatment arms. If prioritisation of classes changes, an adaptive design allows treatment arms to be added or removed to reflect this. Glo-BNHL has an adaptive Bayesian design that facilitates efficient “GO/No-GO” decisions even with small numbers of participants registered into each arm and incorporates an initial stage evaluating efficacy followed potentially by an expansion stage to provide confirmatory analysis. Glo-BNHL is led by the UK with national coordinating centres in Australasia, Europe, and North America. Participants 25 years or younger with histologically proven mature B-NHL at initial diagnosis and radiologically and/or histologically proven B-NHL at first or subsequent relapse, or with refractory B-NHL, who have a performance status ≥ 50 (Karnofsky/Lansky) are eligible. The primary outcomes are occurrence of an objective response (OR) after 12 weeks of treatment with BsAbs (Treatment Arm I); occurrence of complete response within a maximum of three cycles of treatment with ADCs (Treatment Arm II); and occurrence of OR following CAR T-cell infusion (Treatment Arm III). The first agents to be evaluated are odronextamab (Treatment Arm I) and loncastuximab tesirine combined with modified R-ICE (Treatment Arm II). In this rare cancer setting, Glo-BNHL presents a unique opportunity to evaluate multiple promising novel agents within the same trial. It is designed to generate sufficient evidence to be practice-changing. Clinicaltrials.gov: NCT05991388 . Registration date: 24-Jul-2023.