The goal of this clinical trial is to see if a new combination of standard of care radiotherapy treatment prior to administering the study drugs obinutuzumab and glofitamab in relapsed/refractory Diffuse Large B Cell Lymphoma patients is effective. The main question it aims to answer is:
If you are able to tolerate the study treatments, and whether your cancer responds to the study treatment, compared with other reported studies of standard care treatments.
Participants will have three parts they need to complete over a 5 year period.
* Screening period over a 28 day period * Treatment period - Radiotherapy followed by 12 treatment cycles every three weeks (total time approx. 37 weeks) * Follow up, up to 4 years. Additional PET imaging studies will be performed in a cohort of patients (up to 6) who are willing to undergo infusions of 89Zr-Df-Crefmirlimab and 18F-Granzyme B for evaluation of the impact of radiotherapy plus glofitamab with relapsed diffuse large B-cell lymphoma.
Age 18 years.
Histologically proven relapsed/refractory CD20+ve DLBCL or a recognised subtype, including follicular large B-cell lymphoma and high grade B-cell lymphoma.
Prior systemic treatment: ≥2 lines OR after 1 line AND autologous stem cell transplant/CAR-T ineligible
Eastern Collaborative Oncology Group (ECOG) performance status 0 to 2.
Patient has failed only one prior line of therapy and is a candidate for stem cell
Transplantation or CAR-T cell therapy
Excessively bulky or rapidly progressive disease that, in the opinion of the investigator, requires rapid debulking or is unsafe to be irradiated
Richter's transformation from CLL. Transformation from other low-grade histology (e.g. Follicular lymphoma, Marginal zone lymphoma etc) is permitted
Single group
Glofitamab
DrugGlofitamab is the treatment of adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after two or more prior systemic therapies.
Radiotherapy
Radiation25 Gy in 5 fractions.
Obinutuzumab
DrugObinutuzumab as a pre-treatment to reduce the risk of CRS induced by glofitamab is approved in Australia.
89Zr-Df-crefmirlimab
Other intervention89Zr-Df-crefmirlimab infusion and imaging (24hrs+/- 4 hours) - must be at least 5 days prior to the first fraction of radiotherapy of study treatment, A second infusion of 89Zr-Df-crefmirlimab and imaging will be after Cycle 2 (15 days +/- 3 days)
18F-granzyme B
Other interventionEligible participants will receive an initial injection of 18F-CSB-321 followed by PET imaging up to 14 days prior to commencing therapy. 370 MBq (±10%) of 18F-CSB-321 is injected, without the need of pre-medications. Participants will be monitored for adverse events up to 2 hours post-injection.
Complete Response Rate After Radiotherapy and Glofitamab Treatment
The study will assess how many participants achieve a complete metabolic response after radiotherapy and 12 cycles of glofitamab treatment, without severe side effects that require stopping treatment early
Safety assessment through adverse events
The study will assess the safety and effectiveness of treatment, including side effects such as cytokine release syndrome (CRS) and infections. All adverse events will be graded according to CTCAE v 5.0.
Assessment of impact of side effects on patient's quality of life - EORTC-QLQ-C30
The EORTC QLQ-C30 is a patient-reported outcome measure that evaluates health-related quality of life across multiple domains. It includes five functional domains, physical, role, cognitive, emotional, and social functioning. As well as nine symptom domains covering fatigue, pain, nausea and vomiting, dyspnoea, appetite loss, insomnia, constipation, diarrhoea, and financial impact. In addition, it contains a global health status/quality-of-life scale. Responses are recorded using both 4-point and 7-point rating scales. Changes in global health status from baseline will be analysed. For the functional domains, higher scores indicate better levels of functioning, while higher scores on symptom domains represent greater symptom severity or burden.
Overall Toxicity (all grades)
Overall Toxicity (all grades) and adverse events of special interest of treatment will be collected and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0.
Overall Response Rate to study treatment
Overall Response Rate as defined by the number of subjects with a best overall response of complete remission (CR), partial remission (PR) as assessed by CT plus PET, defined by the Lugano Response assessment for Non Hodgkin Lymphoma, at the completion of treatment or during the study.
Blood markers linked to treatment response and side effects
Blood samples will be used for biomarker analysis, which will include but is not limited to: DNA (deoxyribonucleic acid) genotyping, RNA (ribonucleic acid) and/or miRNA (micro-RNA) expression, ctDNA analysis and soluble serum/plasma factors related to immune and tumour response in order to correlate potential biomarkers with treatment responses and toxicity.
Gut bacteria changes linked to treatment response and side effects
Studying whether changes in gut bacteria are associated with how patients respond to treatment and their risk of side effects.
Advanced PET scan measures
Change from baseline in PET radiomic features associated with intra-tumoral activated T-cell infiltration after cycle 2 of glofitamab. CT imaging in this instance will be used to 'locate' the tumor and will not be used for diagnostic purposes.
Tissue markers linked to treatment response and side effects
Tissue samples will be collected to evaluate the role of prognostic and predictive biomarkers. Tissue samples will be collected (core biopsies-minimum of 3, ideally 5-6 cores- or surgical biopsies as part of the standard study assessments and should be preserved as formalin-fixed paraffin-embedded (FFPE) specimens.
Click on the lead sponsor to view all of their trials.
Olivia Newton-John Cancer Research Institute
Lead sponsor
Fiona Stanley Hospital
Collaborator
Princess Alexandra Hospital, Brisbane, Australia
Collaborator
Austin Health
Collaborator
Townsville Hospital
Collaborator
Hoffmann-La Roche
Collaborator
Flinders Medical Centre
Collaborator
This trial is not recruiting at the moment. You can still explore other options:
