NCT07489989

Enhancing CAR-T Cell Therapy Efficacy in B-cell Lymphoma Via Chidamide and PD-1 Inhibitor Combination.

Chidamide-based Combination With PD-1 Blockade: A Synergistic Strategy to Improve CAR-T Cell Therapy Outcomes for B-cell Lymphoma.

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: Daihong Liu · Academic / Other
• Sex: All
• Age: 18 Years – 85 Years
• Healthy volunteers: Not accepted

Summary

B-cell non-Hodgkin lymphoma (B-NHL) is one of the most common malignancies in China, with approximately 100,000 new cases diagnosed annually. Although immunochemotherapy, novel small-molecule targeted agents, and hematopoietic stem cell transplantation have significantly improved outcomes for patients with B-cell malignancies, nearly half of patients still experience drug resistance and relapse. In high-risk aggressive B-cell lymphoma, the 5-year survival rate remains around 50%. Previous clinical guidelines recommended autologous hematopoietic stem cell transplantation as first-line consolidation therapy for high-risk patients; however, multiple studies have demonstrated that even after autologous transplantation, nearly half of these patients relapse and succumb to the disease. Chimeric antigen receptor T (CAR-T) cell therapy has achieved objective response rates of approximately 50% in relapsed/refractory lymphoma, particularly in B-cell subtypes. Nevertheless, limitations such as tumor immune antigen escape, immunosuppressive effects of the tumor microenvironment (TME) on CAR-T cells, and T-cell exhaustion continue to restrict the durability and efficacy of CAR-T-mediated cytotoxicity. This study evaluates the incorporation of chidamide (an HDAC inhibitor) combined with a PD-1 inhibitor as maintenance therapy following CAR-T cell immunotherapy in patients with relapsed/refractory high-risk aggressive B-cell lymphoma. By implementing an "early intervention" strategy-prompt administration of CAR-T cell therapy after induction treatment for relapsed/refractory high-risk aggressive B-cell lymphoma-and subsequent maintenance with chidamide plus a PD-1 inhibitor, the approach aims to reduce relapse rates and improve overall survival. These strategies are intended to address the current unmet clinical need for improved outcomes in relapsed/refractory high-risk aggressive B-cell lymphoma, where prognosis remains poor despite existing therapies.

Conditions

• Relapsed or Refractory Diffuse Large B-Cell Lymphoma (R/R DLBCL)

Interventions

Type	Name	Description
DRUG	CAR-T Cell Therapy + Chidamide and PD-1 Inhibitor Maintenance	Patients will receive maintenance therapy consisting of Chidamide combined with a PD-1 inhibitor following CAR-T cell infusion. This intervention is designed to upregulate target antigen expression on tumor cells and mitigate antigen escape. By synergistically enhancing the cytotoxic activity and persistence of CAR-T cells, the regimen aims to reduce the risk of relapse and improve long-term clinical outcomes

Timeline

• Start date: 2025-05-15
• Primary completion: 2027-05-15
• Completion: 2027-05-15
• First posted: 2026-03-24
• Last updated: 2026-03-24

Locations

1 site across 1 country: China