This is a prospective, multicenter, single-arm, open-label phase 2 study designed to evaluate the efficacy and safety of chidamide maintenance in adults with newly diagnosed double-expressor diffuse large B-cell lymphoma (DLBCL) who achieve complete response after induction therapy but remain ctDNA minimal residual disease (MRD)-positive. Eligible participants will receive oral chidamide 20 mg on Days 1, 4, 8, and 11 of each 21-day cycle. ctDNA MRD will be assessed every 12 weeks. Treatment will continue until two consecutive MRD-negative assessments, disease progression, intolerable toxicity, withdrawal of consent, or completion of 2 years of maintenance. The primary objectives are to evaluate ctDNA MRD negativity and 2-year progression-free survival. Secondary objectives include event-free survival, overall survival, and safety.

Patients with double-expressor DLBCL remain at increased risk of relapse despite achieving complete response after induction therapy. ctDNA-based MRD assessment may identify a subgroup with persistent molecular disease who are at particularly high risk for recurrence. Chidamide is an oral selective histone deacetylase inhibitor with potential antitumor and immune-modulating activity in B-cell lymphomas.

This prospective, multicenter, single-arm, open-label phase 2 study will enroll adult patients with newly diagnosed CD20-positive double-expressor DLBCL, defined by MYC expression >=40% and BCL2 expression >=50% by immunohistochemistry, who achieve complete response after initial induction therapy but remain ctDNA MRD-positive. Participants will receive chidamide 20 mg orally on Days 1, 4, 8, and 11 of each 21-day cycle. ctDNA MRD will be monitored every 12 weeks. Treatment will stop upon two consecutive MRD-negative assessments, disease progression, intolerable toxicity, withdrawal of consent, or completion of 2 years of maintenance. The study will evaluate ctDNA MRD negativity rate and 2-year progression-free survival as primary endpoints, with event-free survival, overall survival, and safety as secondary endpoints.

Inclusion Criteria:

• Histologically confirmed diffuse large B-cell lymphoma, CD20-positive.
• Double-expressor lymphoma confirmed by pathology, defined as MYC expression >=40% and BCL2 expression >=50% by immunohistochemistry.
• Complete response after initial induction therapy.
• Age >=18 and <=80 years.
• ECOG performance status 0-2.
• No prior history of malignant tumor and no concurrent malignancy.
• International Prognostic Index (IPI) score >1.
• ctDNA MRD-positive at screening/enrollment.
• Life expectancy of at least 6 months, in the opinion of the investigator.
• Written informed consent provided before any study-specific procedure.

Exclusion Criteria:

• Failure to achieve complete response after initial induction therapy.
• Prior organ transplantation.
• Uncontrolled coagulopathy or active bleeding.
• Uncontrolled cardiovascular or cerebrovascular disease, including left ventricular ejection fraction <50%, connective tissue disease, or severe active infection.
• Major organ surgery within 6 weeks before screening.
• Screening laboratory abnormalities not attributable to lymphoma, including: neutrophil count <1.5 x 10^9/L; platelet count <80 x 10^9/L (or <50 x 10^9/L in patients with bone marrow involvement); total bilirubin >1.5 x upper limit of normal; ALT/AST >2.5 x upper limit of normal, or >5 x upper limit of normal in patients with hepatic involvement; serum creatinine >1.5 x upper limit of normal.
• Active hepatitis B not meeting protocol-defined virologic criteria for enrollment; patients with positive HBsAg or positive HBcAb require HBV DNA testing and must meet protocol-specified thresholds.
• HIV infection.
• Ongoing antitumor therapy for lymphoma or another malignancy.
• Drug abuse or chronic alcohol abuse that may interfere with study evaluation.
• Psychiatric illness or any condition resulting in inability to comply with the protocol.
• Requirement for ongoing treatment with strong or moderate CYP3A inhibitors or inducers; patients exposed to these agents within 7 days before first study dose, or within fewer than 5 half-lives, are not eligible.
• Inability to swallow capsules or clinically significant gastrointestinal disorders that may affect drug absorption, including malabsorption syndrome, bariatric surgery, inflammatory bowel disease, or partial/complete bowel obstruction.
• Any other uncontrolled medical condition that, in the investigator's judgment, may compromise safety, interfere with oral drug absorption or metabolism, or place the participant at excessive risk.

A decision regarding sharing de-identified individual participant data has not yet been made. This is an investigator-initiated, multicenter study involving ctDNA MRD-related data, and the sponsor has not yet finalized the data-sharing governance, de-identification standards, request review process, and applicable data-sharing agreements across participating sites. The possibility of sharing de-identified data may be considered after study completion and database lock, in accordance with participant consent, ethics committee requirements, institutional policies, and applicable regulations.