Enhancing CAR-T Cell Therapy Efficacy in B-cell Lymphoma Via Chidamide and PD-1 Inhibitor Combination.
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-85
SponsorDaihong Liu
About this trial
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.
Eligibility criteria
Qualifiers
Partial response (PR) after induction therapy with a standard first-line chemotherapy regimen (e.g., R-CHOP for 4-6 cycles); or
Complete response (CR) after standard first-line induction therapy, but with high-risk features present at initial diagnosis.
High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements ("double-hit" or "triple-hit") confirmed by fluorescence in situ hybridization (FISH);
High-grade B-cell lymphoma with 11q aberration (Burkitt-like lymphoma with 11q aberration);
Disqualifiers
Prior treatment with any form of chimeric antigen receptor (CAR) T-cell therapy or other genetically modified T-cell therapy.
History of severe immediate-type hypersensitivity reaction to aminoglycoside antibiotics or other drugs.
Known history of human immunodeficiency virus (HIV) infection, active hepatitis B virus (HBV) infection, or any uncontrolled active systemic infection requiring intravenous antibiotics.
Non-hematologic malignancy-related hepatic or renal impairment, including any of the following: ALT > 3 × ULN, AST > 3 × ULN, total bilirubin (TBIL) > 2 × ULN, or creatinine clearance < 30 mL/min.
Trial design
Treatments tested in this trial
- CAR-T Cell Therapy + Chidamide and PD-1 Inhibitor Maintenance
Treatment groups
30 Participants
are divided into 1 treatment groupSponsors and collaborators
Daihong Liu
Lead sponsor
Chinese PLA General Hospital
Sponsor institution
Source ClinicalTrials.gov