Hypofractionation Radiotherapy in Combination With Glofitamab in Relapsed/Refractory Diffuse B-cell Lymphoma With Baseline High Tumor Burden (GLOHRT-01)

May 14, 2026 updated by: Liling Zhang

A Prospective, Single Arm, Phase Ⅱ Study to Evaluate the Efficacy and Safety of Hypofractionation Radiotherapy in Combination With Glofitamab in Relapsed/Refractory Diffuse B-cell Lymphoma With Baseline High Tumor Burden

Glofitamab has shown efficacy and safety in the treatment of patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) and has been approved for marketing in China. However, in patients with baseline high tumor burden, the complete response (CR) rate is relatively lower compared with patients without. There is still a need to improve the efficacy of glofitamab in patients with high tumor burden. Previous studies have shown that hypofractionation radiotherapy (HRT) may induce T cell immune responses and improve the tumor microenvironment . Evidence shows that radiotherapy (RT) improves chimeric antigen receptor T-cell (CAR-T) efficacy as a bridging therapy . Based on the experience of RT combined with CAR-T, bispecific antibodies, as another T-cell therapy, may also demonstrate synergistic effects when combined with HRT, especially in those patients with bulky disease. This study will enroll R/R DLBCL patients with high tumor burden to assess the efficacy and safety of glofitamab in combination with HRT and to explore a new treatment model for R/R DLBCL patients with high tumor burden at baseline.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

40

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Hubei
      • Wuhan, Hubei, China, 430022
        • Recruiting
        • Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Signed informed consent.
  • Aged 18-75 years at the time of signing the informed consent, willing to follow and able to complete all study procedures.
  • Expected survival ≥ 12 weeks.
  • ECOG performance status score of 0-2 points ;
  • Patients with CD20-positive DLBCL confirmed by pathological histology; (unspecified DLBCL, HGBCL, PMBCL, FL-transformed DLBCL).
  • R/R DLBCL who have received at least one line of systemic treatment (including at least 2 cycles of rituximab-containing immunochemotherapy).
  • Baseline high tumor burden, defined as tumor diameter > 6 cm and/or TMTV > 128.7 mL .
  • HIV test results were negative at screening, except for the following: HIV-positive patients who have been receiving stable antiretroviral therapy and CD4 count ≥ 200/µL before enrollment Patients with undetectable viral load can be enrolled.
  • Women of childbearing age with negative urine or blood pregnancy test within 7 days before enrollment need to agree to take effective contraceptive measures during treatment and follow-up.

Exclusion Criteria:

  • Individuals who have drug allergies or metabolic disorders to the drugs in this protocol.
  • Previous recipients of allogeneic organ transplants.
  • Individuals who received systemic immunotherapy within 4 weeks or 5 half-lives (whichever is shorter) of the drug.
  • Anti-cancer drug treatment within 28 days before the start of treatment
  • Prior radiotherapy in the mediastinum/pericardium area; radiation therapy for non-target lesion sites is allowed.
  • History of severe or extensive cardiovascular disease.
  • Recent major surgery (within 4 weeks before the start of Cycle 1), excluding diagnostic surgeries.
  • Currently suffering from active CNS lymphoma.
  • Known or suspected history of hemophagocytic lymphohistiocytosis (HLH)
  • Current or previous history of concurrent Waldenström's macroglobulinemia.
  • Known active infection at the time of enrollment in the study.
  • Immune-related adverse events that appeared during prior immunotherapy: ≥Grade 3 adverse events, except for Grade 3 endocrine diseases controlled by alternative therapies. Grade 1 or 2 adverse events that did not return to baseline levels after stopping treatment.
  • History of autoimmune diseases (long-standing or well-controlled autoimmune diseases, hypothyroidism, immune thrombocytopenic purpura, and well-controlled Type I diabetes are excluded).
  • Abnormal coagulation function: INR or PT >1.5× upper limit of normal (ULN), PTT or aPTT >1.5× ULN.
  • Suspected or latent tuberculosis (confirmed by positive IFNγ release test)
  • Active hepatitis B virus (HBV) infection/positive HCV RNA test for hepatitis C virus (HCV)/HIV seropositive.
  • Previously suffered from other invasive malignancies, excluding early-stage cervical cancer, basal cell carcinoma of the skin, and thyroid cancer .
  • Pregnant or breastfeeding, or planning to become pregnant during the study period or within 18 months after pre-treatment with obinutuzumab or within 2 months after the last dose of glofitamab (whichever is longer).
  • Other concurrent uncontrolled medical conditions that, in the investigator's opinion, would affect the patient's participation in the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Glofitamab

Utilizing intensity-modulated radiation therapy (IMRT); the radiation field follows the principles of involved site radiation therapy (ISRT). Total RT dose is 30 Gy/6 fraction, once daily, starting 8 days before Obinutuzumab pretreatment.

An initial 1000 mg dose of Obinutuzumab will be administered as pretreatment 7 days prior to the first Glofitamab step-up dose Glofitamab is administered intravenously as step-up doses on day 8 (2.5 mg) and day 15 (10 mg) of cycle 1, followed by a dose of 30 mg on day 1 of cycles 2 through 8, maximum of 12 cycles (Q3W). The efficacy is evaluated after 2 cycles of Glofitamab. Those with disease progression will be withdrawn from the study. The remaining patients continue with an additional two cycles of Glofitamab (4 cycles in total) and then perform efficacy assessment. If the patients achieve a CR or PR, they will continue to complete the remaining treatment as planned.
Drug: Glofitamab + Obinutuzumab

Obinutuzumab An initial 1000 mg dose of obinutuzumab will be administered as pretreatment 7 days prior to the first glofitamab step-up dose

Glofitamab:

Glofitamab was administered intravenously as step-up doses on day 8 (2.5 mg) and day 15 (10 mg) of cycle 1, followed by a dose of 30 mg on day 1 of cycles 2 through 8, maximum of 12 cycles (Q3W). The efficacy is evaluated after 2 cycles of glofitamab. Those with disease progression will be withdrawn from the study. The remaining patients continue with an additional two cycles of glofitamab (4 cycles in total) and then perform efficacy assessment. If the patients achieve a CR or PR, they will continue to complete the remaining treatment as planned. Patients are recommended to treat for 12 cycles (at least 8 cycles, depending on tumor regression in patients) or until disease progression or unacceptable toxicity, whichever occurs first

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete remission rate
Time Frame: From enrollment to the end of treatment at 8 cycles (each cycle is 21 days)
defined as the percentage of patients whose best overall response was a CR according to the 2014 Lugano Response Criteria (Cheson, et al. 2014); as determined by the investigator
From enrollment to the end of treatment at 8 cycles (each cycle is 21 days)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Best response rate
Time Frame: From enrollment to the end of treatment at 8 cycles (each cycle is 21 days)
defined as the proportion of patients whose best overall response is a PR or CR using 2014 Lugano Response Criteria (Cheson, et al. 2014)
From enrollment to the end of treatment at 8 cycles (each cycle is 21 days)
DoCR
Time Frame: from the initial occurrence of a documented CR until documented disease progression or death due to any cause, assessed up to 48 months
defined as the time from the initial occurrence of a documented CR until documented disease progression or death due to any cause, whichever occurs first,. This will be evaluated using investigator assessment based on the 2014 Lugano Classification (Cheson, et al. 2014).
from the initial occurrence of a documented CR until documented disease progression or death due to any cause, assessed up to 48 months
PFS
Time Frame: the time from the first study treatment to the first occurrence of disease progression or death from any cause, whichever occurs first, assessed up to 48 months
defined as the time from the first study treatment to the first occurrence of disease progression or death from any cause, whichever occurs first. PFS will be assessed by the investigator, using the 2014 Lugano classification (Cheson et al. 2014
the time from the first study treatment to the first occurrence of disease progression or death from any cause, whichever occurs first, assessed up to 48 months
OS
Time Frame: the time from the first study treatment to the date of death from any cause, assessed up to 48 months
defined as the time from the first study treatment to the date of death from any cause.
the time from the first study treatment to the date of death from any cause, assessed up to 48 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Liling Zhang

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2025

Primary Completion (Estimated)

August 31, 2028

Study Completion (Estimated)

August 31, 2028

Study Registration Dates

First Submitted

February 11, 2025

First Submitted That Met QC Criteria

March 6, 2025

First Posted (Actual)

March 10, 2025

Study Record Updates

Last Update Posted (Actual)

May 15, 2026

Last Update Submitted That Met QC Criteria

May 14, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UHCT241108

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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