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OncoMatch/Clinical Trials/NCT07489989

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

Is NCT07489989 recruiting? Yes, currently enrolling (May 2026). This Phase 2 trial studies CAR-T Cell Therapy + Chidamide and PD-1 Inhibitor Maintenance for relapsed or refractory diffuse large b-cell lymphoma (r/r dlbcl).

Phase 2RecruitingDaihong LiuNCT07489989Data as of May 2026

Treatment: CAR-T Cell Therapy + Chidamide and PD-1 Inhibitor MaintenanceB-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.

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Extracted eligibility criteria

Cancer type

Diffuse Large B-Cell Lymphoma

Non-Hodgkin Lymphoma

Biomarker criteria

Required: CD19 overexpression (positive)

CD19 and/or CD22-positive large B-cell lymphoma

Required: CD22 overexpression (positive)

CD19 and/or CD22-positive large B-cell lymphoma

Allowed: MYC rearrangement

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)

Allowed: BCL2 rearrangement

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)

Allowed: BCL6 rearrangement

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)

Allowed: CD5 overexpression

CD5 positivity by immunohistochemistry

Allowed: MYC overexpression

Dual expression of MYC and BCL2 by immunohistochemistry (recommended thresholds: MYC ≥ 40% and BCL2 ≥ 50%)

Allowed: BCL2 overexpression

Dual expression of MYC and BCL2 by immunohistochemistry (recommended thresholds: MYC ≥ 40% and BCL2 ≥ 50%)

Allowed: TP53 mutation

TP53 mutation detected by gene sequencing

Performance status

ECOG 0–2(Ambulatory, capable of self-care)

Prior therapy

Must have received: anti-cd20 monoclonal antibody

Must have received: anthracycline-containing combination chemotherapy

Cannot have received: car-t cell therapy

Lab requirements

Blood counts

Hemoglobin ≥60 g/L (transfusion permitted); ANC ≥1,000/μL; platelet count ≥45,000/μL

Kidney function

Serum creatinine ≤1.5 × ULN or creatinine clearance ≥60 mL/min (Cockcroft-Gault)

Liver function

Total bilirubin (TBIL) ≤1.5 × ULN (except Gilbert's syndrome); ALT and AST ≤2.5 × ULN

Cardiac function

LVEF ≥50% by ECHO, no pericardial effusion, no clinically significant arrhythmias

Adequate hepatic, renal, cardiac, and pulmonary function, meeting all of the following: TBIL ≤1.5 × ULN (except Gilbert's syndrome); ALT and AST ≤2.5 × ULN; Serum creatinine ≤1.5 × ULN or CCr ≥60 mL/min; LVEF ≥50% by ECHO, no pericardial effusion, no clinically significant arrhythmias; Baseline oxygen saturation by pulse oximetry >92% on room air; No clinically significant pleural effusion.

Structured fields extracted by AI. May contain errors — verify against the official protocol.

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