Radiotherapy in Combination With Glofitamab in Relapsed/Refractory Diffuse Large B Cell Lymphoma

Conditions

• Relapsed /Refractory DLBCL

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Glofitamab — DRUG
  Glofitamab is the treatment of adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after two or more prior systemic therapies.
• Radiotherapy — RADIATION
  25 Gy in 5 fractions.
• Obinutuzumab — DRUG
  Obinutuzumab as a pre-treatment to reduce the risk of CRS induced by glofitamab is approved in Australia.
• 89Zr-Df-crefmirlimab — OTHER
  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)
• 18F-granzyme B — OTHER
  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.

Study Details

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.

Key Dates

Start date

Dec 31, 2026

Status verified

Jun 2026

Primary completion

Dec 31, 2031

Completion

Dec 31, 2032

Study Design

Enrollment

40 participants (estimated)

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Arms

• Experimental: Intervention
  Radiotherapy will be delivered at 25Gy in 5 fractions to all PET/CT-avid nodal, and selected extranodal disease sites \>1.5cm diameter. Following RT, patients will commence systemic therapy and receive one dose of 1000mg obinutuzumab (IV) followed by an initial step-up dose ramp of glofitamab on day 15 and day 22 (D15 2.5mg IV, D22 10mg IV), then 30mg intravenously every 3 weeks for cycles 2-12. Participants will have FDG PET/CT scans at the start of the study, after cycles 2, 4/5 and 8/9, at the end of treatment after cycle 12, and again if the disease returns (where possible). For up to 6 patients at approved sites, an additional PET sub-study will involve two extra scans using each tracer, one before treatment starts and one after cycle 2. After finishing treatment, participants will attend follow-up clinic visits every 3 months during the first year, and then every 6 months from years 2 to 5.

Primary Outcome Measure

Complete Response Rate After Radiotherapy and Glofitamab Treatment [ Time Frame: 37 weeks ]