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

NCT07634289 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: ONJ2026-003
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Relapsed /Refractory DLBCL

Keywords

relapsed/refractory Diffuse Large B Cell lymphoma; Raditherapy; glofitamab; Radio-GLO; DLBCL; Obinutuzumab - Gazyva, Gazyvaro; Columvi

Outcome Measures

Primary Outcomes (1)

• 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

  37 weeks

Secondary Outcomes (9)

• Safety assessment through adverse events

  5 years total

• Assessment of impact of side effects on patient's quality of life - EORTC-QLQ-C30

  5 years

• Overall Toxicity (all grades)

  5 years

• Overall Response Rate to study treatment

  5 years

• Time to Treatment failure

  5 years

Other Outcomes (4)

• Blood markers linked to treatment response and side effects

  5 years

• Gut bacteria changes linked to treatment response and side effects

  5 years

• Advanced PET scan measures

  12 months

Study Arms (1)

Intervention

EXPERIMENTAL

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.

Drug: Glofitamab; Radiation: Radiotherapy; Drug: Obinutuzumab; Other: 89Zr-Df-crefmirlimab; Other: 18F-granzyme B

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.

Also known as: Columvi

Intervention

Radiotherapy RADIATION

25 Gy in 5 fractions.

Intervention

Obinutuzumab DRUG

Obinutuzumab as a pre-treatment to reduce the risk of CRS induced by glofitamab is approved in Australia.

Also known as: Gazyva

Intervention

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)

Also known as: 89Zr-DF-IAB22M2C

Intervention

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.

Also known as: [AI18F]-NODA-CSB-321, CSB-321

Intervention

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Measurable FDG avid disease on baseline PET/CT scan
• At least one site of active, PET positive disease that can be safely irradiated. Patients with disease only in previously irradiated sites that cannot be safely irradiated again due to tissue tolerance will be excluded.
• Adequate bone marrow function including:
• Haemoglobin \>8.0 g/dL
• White cell count (WCC) ≥2000/μL
• Neutrophils \>1.0 x 109/L
• Platelets \>75 x 109/L at the time of study entry, unless attributed to lymphoma. Red cell transfusion is permitted.
• Adequate renal function with serum creatinine ≤1.5 x ULN or creatinine clearance (CrCl) ≥ 45mL/min (using Cockcroft-Gault formula, Modification of Diet in Renal Disease Study Equation, 24hr urine collection, eGFR or a formal nuclear medicine technique) unless attributed to lymphoma (e.g. ureteric obstruction).
• Adequate hepatic function with AST/ALT ≤3x ULN and total bilirubin ≤1.5 x ULN (except subjects with Gilbert syndrome, who can have a total bilirubin ≤3 mg/dL or ≤51.3 μmol/L) unless attributed to lymphoma (e.g. liver infiltration or biliary obstruction).
• Adequate left ventricular ejection fraction of \>40% as demonstrated on a Gated Cardiac Blood Pool Scan or echocardiogram.
• Life expectancy \> 3 months.

You may not qualify if:

• 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
• Refractory to prior therapy with glofitamab or other anti-CD3/CD20 bispecific antibodies, defined as progression during or within 3 months of cessation.
• Treatment with radiotherapy, chemotherapy, immunotherapy, immunosuppressive therapy, or any investigational agent for the purposes of treating cancer within 4 weeks or 5 half-lives (whichever is shorter) prior to first study treatment.
• Current central nervous system, meningeal involvement or spinal cord compression by lymphoma. Previous involvement is permitted if there is currently no active CNS disease.
• Patients with active, known or suspected autoimmune disease. Patients with well controlled type I diabetes mellitus, coeliac disease, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, vitiligo or psoriasis not requiring systemic treatment, or other conditions not expected to recur in the absence of an external trigger are permitted to enrol.
• Subjects with a condition requiring systemic treatment with either corticosteroids (\>10mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration without prior discussion with the medical monitor. Inhaled or topical steroids, and adrenal replacement therapy are permitted in the absence of active autoimmune disease.
• Prior solid organ transplantation or allogeneic bone marrow transplantation within 6 months.
• Prior malignancy active within the previous 2 years except for those treated with curative intent and with a \<20% chance of relapse. Low-grade prostate cancer under observation or well controlled on hormone therapy is permitted. Resected or locally treated non-melanoma skin cancer is permitted.
• Uncontrolled or severe cardiovascular disease (NYHA class III or IV heart failure; myocardial infarction within the last 6 months of study entry); unstable angina; unstable cardiac arrhythmias; clinically significant pericardial disease.
• Any other serious active disease or infection that in the opinion of the investigator takes precedence over the DLBCL, or will impact on the ability to deliver study treatment.
• Any positive test result for hepatitis B or hepatitis C virus during screening indicating acute or chronic infection. Latent hepatitis B with undetectable viral load by PCR is allowable provided appropriate anti-viral prophylaxis is given as per institutional guidelines.
• Any positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) unless the viral load is fully suppressed for \>2 years with a CD4 count of \>350x106/L and compliant with antiretroviral therapy.

Sponsors & Collaborators

• Fiona Stanley Hospital: collaborator
• Austin Health: collaborator
• Townsville Hospital: collaborator
• Hoffmann-La Roche: collaborator
• Olivia Newton-John Cancer Research Institute: lead
• Princess Alexandra Hospital, Brisbane, Australia: collaborator
• Flinders Medical Centre: collaborator

Study Sites (5)

Townsville University Hospital

Douglas, Queensland, Australia

Location

Princess Alexandra Hospital

Woolloongabba, Queensland, 4102, Australia

Location

Flinders Medical Centre

Bedford Park, South Australia, 5042, Australia

Location

Austin Hospital

Heidelberg, Victoria, 3084, Australia

Location

Fiona Stanley Hospital

Murdoch, Western Australia, Australia

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

glofitamab; Radiotherapy; obinutuzumab

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 20, 2026
• First Posted: June 8, 2026
• Study Start (Estimated): December 1, 2026
• Primary Completion (Estimated): December 1, 2031
• Study Completion (Estimated): December 1, 2032
• Last Updated: June 8, 2026

Record last verified: 2026-06

Locations

AU (5)