Zanubrutinib, Chidamide, and Rituximab Induction With or Without CHOP Versus R-CHOP in Newly Diagnosed Double-Expressor DLBCL

Korábbi kezelés

• Major surgery within the past 2 months (excluding diagnostic surgery).
• Previous treatment for NHL, including chemotherapy, immunotherapy, radiotherapy, monoclonal antibody therapy, or surgical treatment (excluding diagnostic surgery and biopsy).
• Previous treatment with cytotoxic drugs or anti-CD20 monoclonal antibody therapy for other diseases (e.g., rheumatoid arthritis).
• Use of any monoclonal antibody within 3 months prior to enrollment, participation in other clinical trials with investigational drugs, or vaccination with live attenuated virus vaccines within 1 month prior to enrollment.
• Use of hematopoietic growth factors within 2 weeks prior to enrollment.
• Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infections (excluding nail bed fungal infections) within 4 weeks prior to enrollment, or any major systemic infection requiring intravenous antibiotics or hospitalization (excluding tumor fever).
• Contraindications to any study drug, including previous treatment with anthracyclines; patients with diabetes who cannot tolerate prednisone treatment in this regimen.
• Requirement for continuous treatment with strong CYP3A inhibitors or inducers (see Appendix 6).
• Patients unable to swallow study drugs normally.

Más betegség

• History of other malignancies within the past 5 years, except for squamous cell carcinoma of the skin, basal cell carcinoma of the skin, and carcinoma in situ of the cervix.
• Suspected active or latent tuberculosis.
• History of severe bleeding disorders, such as hemophilia A, hemophilia B, von Willebrand disease, or spontaneous bleeding requiring transfusion or other medical intervention.
• HIV-positive patients. Active HBV-positive and HCV-positive patients, but those with controlled conditions as judged by the investigator may be cautiously enrolled with effective antiviral intervention.
• Other severe diseases that may limit participation in this trial, such as uncontrolled diabetes; severe heart failure (NYHA class II or above); acute coronary syndrome within the past 6 months; coronary revascularization within the past 6 months, such as stent implantation, coronary artery bypass grafting, and other heart and large vessel surgeries; severe arrhythmias including frequent premature ventricular contractions, ventricular tachycardia, rapid atrial fibrillation/flutter, severe bradycardia. Uncontrolled hypertension (greater than 150/100 mmHg). Gastric ulcer (with a risk of perforation as judged by the investigator); active autoimmune diseases; severe hypertension; severe respiratory diseases (e.g., obstructive pulmonary disease and bronchospasm history), such as known interstitial pneumonia or highly suspected interstitial pneumonia; or patients who may interfere with the detection or management of suspected drug-related pulmonary toxicity.
• History of alcohol abuse or drug abuse.
• Allergic constitution, or known allergy to any active ingredient, excipient, or murine products, heterologous proteins included in this study.
• Severe mental illness.

Egyéb

• Special types of DLBCL:Fluid overload-associated large B-cell lymphoma, primary mediastinal large B-cell lymphoma, mediastinal gray zone lymphoma, primary central nervous system (CNS) DLBCL, double-hit DLBCL with BCL2 and MYC rearrangements.
• Transformed DLBCL (e.g., DLBCL transformed from follicular lymphoma, chronic lymphocytic leukemia/small B-cell lymphoma), secondary CNS involvement of DLBCL.
• Patients unable to comply with the study and/or follow-up phases.
• Patients deemed unsuitable for enrollment by the investigator.

• Newly diagnosed MYC/BCL2 double-expressor DLBCL confirmed by pathological histology/clinical imaging, with IHC BCL2 expression ≥50% and MYC expression ≥40%.
• Male or female patients aged 18-65 years.
• ECOG score of 0-2.
• Expected survival time of ≥6 months.
• Must have at least one evaluable or measurable lesion according to the Lugano 2014 criteria [Evaluable lesion: lymph node or extranodal local uptake increased (higher than the liver) on 18F-Fluorodeoxyglucose/Positron Emission Tomography (18FDG/PET) scan, and PET and/or Computed Tomography (CT) features consistent with lymphoma; Measurable lesion: nodal lesion with a long diameter >15mm or extranodal lesion with a long diameter >10mm, with increased 18FDG uptake]. Patients with no measurable lesions and diffuse 18FDG uptake in the liver should be excluded.
• Good major organ function, meeting the following requirements within one week before enrollment: blood routine WBC ≥3×10\^9/L, Hb ≥80g/L, PLT ≥80×10\^9/L; normal cardiac and liver function (total bilirubin ≤1.5 times the upper limit of normal, ALT and AST ≤2.5 times the upper limit of normal), normal renal function (serum creatinine ≤1.5 times the upper limit of normal), and no coagulation abnormalities.
• LVEF ≥50% as measured by echocardiography.
• Women of childbearing potential must have a negative pregnancy test (serum or urine) within 14 days prior to enrollment and be willing to use reliable contraception during the study.
• Subjects voluntarily join the study, sign the informed consent form, have good compliance, and cooperate with follow-up.