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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

Status: Recruiting
Location: See location...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 2
SUMMARY

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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Maximum Age: 75
Healthy Volunteers: f
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• 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.

Locations
Other Locations
China
Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology
RECRUITING
Wuhan
Contact Information
Primary
Liling Zhang
lily1228@sina.com
0086 27 83262660
Time Frame
Start Date: 2025-04-01
Estimated Completion Date: 2028-08-31
Participants
Target number of participants: 40
Treatments
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.
Related Therapeutic Areas
Sponsors
Leads: Liling Zhang

This content was sourced from clinicaltrials.gov