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.
Clinical trial looking at Radiotherapy in combination with glofitimab in relapsed/refractory Diffuse Large B Cell lymphoma. Where Relapsed/refractory diffuse large B-cell lymphoma after ≥ 2 therapies OR after 1 line AND transplant or CAR-T ineligible. The primary end points is to see what proportion of patients who achieve a complete metabolic response in the absence of prohibitive toxicity following radiotherapy (25Gy in 5 fractions) plus 12 cycles of glofitamab therapy with each cycle delivered every 3 weeks. The secondary endpoints are to assess overall toxicity, to evaluate overall response rates, duration of Response (DOR), time to treatment failure, progression free survival, overall survival, patient report outcome measure - Using EORTC QLD-C30, EORTC IL46 and PRO-CTCAE. 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 for evaluation of the impact of radiotherapy plus glofitamab on CD8+ T cell biodistribution in the body and in relapsed diffuse large B-cell lymphoma. Additional PET imaging studies will be performed in a cohort of patients (up to 6) who are willing to undergo infusions of 18F-Granzyme B to image active immune responses to treatment with radiotherapy plus glofitamab in patients with relapsed diffuse large B-cell lymphoma.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
40
Glofitamab is the treatment of adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after two or more prior systemic therapies.
25 Gy in 5 fractions.
Obinutuzumab as a pre-treatment to reduce the risk of CRS induced by glofitamab is approved in Australia.
89Zr-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)
Eligible 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.
Townsville University Hospital
Douglas, Queensland, Australia
Princess Alexandra Hospital
Woolloongabba, Queensland, Australia
Flinders Medical Centre
Bedford Park, South Australia, Australia
Austin Hospital
Heidelberg, Victoria, Australia
Fiona Stanley Hospital
Murdoch, Western Australia, Australia
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
Time frame: 37 weeks
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.
Time frame: 5 years total
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.
Time frame: 5 years
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.
Time frame: 5 years
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.
Time frame: 5 years
Time to Treatment failure
Time to Treatment failure will be calculated from the date of study enrolment until a progression event occurs. Progression events are defined as clinical or radiological documented disease progression.
Time frame: 5 years
Progression-free Survival
Progression-free Survival will be calculated from the date of study enrolment until a progression event occurs, or death from any cause. Patients alive without progression will be censored at date last known to be alive.
Time frame: 5 years
Overall survival
Overall survival will be measured from study entry to date of death from any cause; surviving patients will be censored at date last known to be alive.
Time frame: 5 years
Assessment of impact of side effects on patient's quality of life - PRO-CTCAE
PRO-CTCAE assessments will be analysed to evaluate data integrity, describe baseline symptom burden, monitor symptom trajectories over time, assess the emergence and evolution of patient-reported adverse events, and explore concordance between patient-reported outcomes and investigator-rated adverse events. Results will be summarized descriptively by reporting the frequency and percentage of participants selecting each response level for each PRO-CTCAE item. Comparisons between treatment arms will be undertaken at the individual question level.
Time frame: 5 years
Assessment of impact of side effects on patient's quality of life - EORTC-IL4
The EORTC-IL4 is a disease-specific quality-of-life instrument developed to supplement the EORTC QLQ-C30 by capturing additional symptoms and concerns relevant to the study population. Questionnaire responses will be summarised descriptively at each assessment time point. Scores will be calculated and transformed according to EORTC scoring guidelines, where applicable. Changes from baseline will be evaluated over time to assess the impact of treatment on patient-reported symptoms and health-related quality of life. Higher scores on symptom-related items indicate a greater symptom burden or level of concern, whereas higher scores on functioning-related items indicate better functioning and quality of life.
Time frame: 5 years
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