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 Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
40
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 Those with disease progression will be withdrawn from the study.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
Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology
Wuhan, Hubei, China
RECRUITINGComplete remission rate
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
Time frame: From enrollment to the end of treatment at 8 cycles (each cycle is 21 days)
Best response rate
defined as the proportion of patients whose best overall response is a PR or CR using 2014 Lugano Response Criteria (Cheson, et al. 2014)
Time frame: From enrollment to the end of treatment at 8 cycles (each cycle is 21 days)
DoCR
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).
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
PFS
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
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
OS
defined as the time from the first study treatment to the date of death from any cause.
Time frame: the time from the first study treatment to the date of death from any cause, assessed up to 48 months
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