Tests a new drug combination against standard chemotherapy for newly diagnosed lymphoma

Trial details

Who runs it

Li Zhiming

Trial code

NCT06890585

Record updated

24 March 2025

Original description

Zanubrutinib, as a new generation of BTK inhibitors, has shown more potent antitumor activity and lower adverse reactions than ibrutinib in head-to-head clinical studies, which make it a promising regimen for B cell lymphoma. Chidamide is an oral subtype-selective histone deacetylase inhibitor.Read full original descriptionShow less

A Randomized, Multicenter, Open-Label Phase II Clinical Study Comparing the Efficacy and Safety of Zanubrutinib, Chidamide, and Rituximab Induction Therapy Sequentially Combined With or Without CHOP Versus R-CHOP in the First-Line Treatment of Patients With Newly Diagnosed Double-Expressor Diffuse Large B-cell Lymphoma

Zanubrutinib, as a new generation of BTK inhibitors, has shown more potent antitumor activity and lower adverse reactions than ibrutinib in head-to-head clinical studies, which make it a promising regimen for B cell lymphoma. Chidamide is an oral subtype-selective histone deacetylase inhibitor.

This Randomized, Multicenter, Open-Label Phase II Clinical Study is comparing the efficacy and safety of Zanubrutinib, Chidamide, and Rituximab induction therapy sequentially combined with or without CHOP versus R-CHOP in the first-line treatment of patients with newly diagnosed double-expressor DLBCL.

Inclusion: 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.

Exclusion: 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; 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; 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.

ClinicalTrials.gov NCT06890585