The purpose of this study is to determine the efficacy and safety of CD22/CD19-targeted CAR-T cell immunotherapy as consolidation therapy after second-line treatment in patients with high-risk aggressive B-cell lymphoma.
Only a proportion of patients with aggressive B-cell lymphoma can achieve complete response with standard first-line immunochemotherapy such as R-CHOP, and a considerable number of patients experience relapse or disease progression, facing challenges such as drug resistance and poor prognosis. According to previous National Comprehensive Cancer Network guidelines, patients with high-risk diffuse large B-cell lymphoma (DLBCL) who achieve complete response after first-line induction therapy may receive consolidation treatments such as autologous stem cell transplantation (ASCT) or involved-site radiation therapy (ISRT). However, evidence from the SWOG 9704 study demonstrated that, among patients with intermediate-high or high-risk disease who achieved at least partial response after first-line therapy, ASCT consolidation did not significantly improve progression-free survival (PFS) or overall survival (OS) in the intermediate-high-risk group, with limited benefit observed only in selected high-risk populations. Similarly, the DLCL04 study showed that patients with an age-adjusted International Prognostic Index (aaIPI) score of 2-3 who achieved complete or partial response after first-line therapy did not derive significant benefit from ASCT consolidation. In the 2024 NCCN guidelines for DLBCL, consolidation strategies after first-line therapy have been largely de-escalated, with recommendations mainly limited to observation or localized radiotherapy in selected cases. For patients who relapse or are refractory after first-line treatment, second-line salvage therapy remains the standard approach; however, even after achieving response to second-line therapy, patients with high-risk features still face a substantial risk of disease progression, and there is currently no well-established consolidation strategy to improve long-term outcomes in this setting. Chimeric antigen receptor T-cell (CAR-T) immunotherapy has demonstrated remarkable efficacy in relapsed/refractory B-cell malignancies. As a result, CAR-T therapy has been increasingly explored not only as a salvage treatment but also as a potential consolidation strategy. Compared with autologous hematopoietic stem cell transplantation, CAR-T therapy allows for more controllable management of treatment-related toxicities, such as cytokine release syndrome and neurotoxicity, using immunosuppressive agents including glucocorticoids and tocilizumab. In addition, ASCT is associated with higher risks of treatment-related complications, including infection, bleeding, and non-relapse mortality (NRM). Therefore, for patients with high-risk aggressive B-cell lymphoma who achieve partial or complete response after second-line therapy, there remains an unmet clinical need for effective consolidation strategies to further reduce relapse risk and improve survival outcomes. Based on these considerations, this study aims to explore the efficacy and safety of CD22/CD19-targeted CAR-T cell immunotherapy as consolidation therapy following second-line treatment in patients with high-risk aggressive B-cell lymphoma, with the goal of improving prognosis and providing a novel therapeutic option in this setting.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Patients who achieved complete response (CR) after standard second-line chemotherapy will receive CD19/CD22 CAR-T cell immunotherapy as consolidation treatment. Autologous T cells will be collected and genetically modified to express chimeric antigen receptors targeting CD19 and CD22. Following lymphodepleting chemotherapy, patients will receive a single intravenous infusion of CD19/CD22 CAR-T cells.
Chinese PLA General Hospital, Beijing, Beijing 100853
Beijing, China
RECRUITING1-year progression free survival rate (1-year-PFSR)
The 1-year progression-free survival rate (1-year PFSR) is defined as the proportion of patients who are alive and progression-free at 1 year after CAR-T cell infusion.
Time frame: 1 year after treatment
overall survival (OS)
Overall survival (OS) refers to the time from the start of treatment to the death of the patient for any reason.
Time frame: 2 years after treatment
progression free survival (PFS)
Progression free survival (PFS) refers to the time from treatment to the first lymphoma progression or death of the patient for any reason.
Time frame: 2 years after treatment
time to progression (TTP)
Time to progression (TTP) refers to the time from treatment to the first lymphoma progression.
Time frame: 2 years after treatment
disease free survival (DFS)
Disease free survival (DFS) refers to the time from treatment to the first lymphoma recurrence.
Time frame: 2 years after treatment
event free survival (EFS)
Event Free Survival (EFS) is a commonly used endpoint indicator in clinical trials to evaluate the survival time of patients without any adverse events during a specific time period. These adverse events include but are not limited to disease progression, death, treatment plan changes, and the occurrence of serious side effects.
Time frame: 2 years after treatment
Relapse Rate
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The recurrence rate refers to the proportion of patients with lymphoma recurrence after treatment.
Time frame: 2 years after treatment
Incidence and Severity of Treatment-Emergent Adverse Events
Include cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), hematologic toxicities (anemia, leukopenia, neutropenia, thrombocytopenia), infections, electrolyte abnormalities, liver and renal function abnormalities, and other laboratory abnormalities.
Time frame: 2 years after treatment