Zanubrutinib in Maintenance Therapy of DLBCL Patients With Initial Remission

• Status: Not yet recruiting
• Trial end date: 2026-07-30
• Target enrollment: 0
• Participant gender: All

Summary

This trial is a single-center, single-arm, prospective clinical study to investigate the efficacy and safety of zanubrutinib maintenance therapy in patients with diffuse large B-cell lymphoma (DLBCL) in Initial remission. The patients were divided into two categories: 1) Zanubrutinib maintenance therapy was started after R-CHOP induction and consolidation therapy reached maximum efficacy; 2) Initiate zanubrutinib maintenance therapy after maximal response to induction and consolidation therapy with or without rituximab (R-chemo). Therefore, the data in this study will reflect the efficacy and safety of zanubrutinib in the maintenance treatment of DLBCL patients with initial remission, and will provide new insights into the clinical application of zanubrutinib.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: LanZhou University
• Collaborator: Beigene (Beijing) Biotechnology Co., Ltd
• Treatments: Zanubrutinib

Criteria

Inclusion Criteria:

1. Patients with DLBCL who are diagnosed according to the 2021 NCCN Guidelines for B-cell Lymphoma, aged ≥18 years;

2. Don't received treatment;

3. Measurable lesions: at least 1 lymph node lesion > 1.5 cm in longest dimension, or at least 1 extranodal lesion > 1.0 cm in longest dimension, and at least 2 measurable lesions accurately measured vertical diameter;

4. Clinical stage II (not suitable for local radiotherapy), III, IV (Ann Arbor stage); Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2;

5. Intermediate-high-risk /high-risk group: International Prognostic Index (IPI) score 3-5, aa-IPI score 2-3 or NCCN-IPI score ≥4;

6. Expression of MYC, BCL-2 and BCL-6 (detected by immunohistochemistry, qualitative or quantitative detection), or MYD88, CD79A/CD79B [9] and TP53 genetic abnormality [10];

7. Patients with non-bone marrow invasion:

1. The absolute value of neutrophils≥1.5×109/L

2. Platelets ≥100×109/L (judged by the investigator according to the condition, the minimum can be ≥75×109/L)

3. Hemoglobin ≥ 90g/L;

9. The level of biochemical indicators meets the following requirements:

1. Renal function: endogenous creatinine clearance rate > 30ml/min;

2. Liver function: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × upper limit of normal range (ULN); total bilirubin ≤ 2 × ULN (unless Gilbert syndrome is diagnosed);

3. Coagulation function: international normalized ratio (INR) ≤ 1.5 and activated partial thromboplastin time (aPTT) ≤ 1.5×ULN; 9. life expectancy ≥ 3 months; 10. The patient and family members agree and sign an informed consent form.

Exclusion Criteria:

1. Lymphoma with central nervous system invasion or mediastinal large B-cell lymphoma, diagnosis or treatment of malignant tumors other than DLBCL;

2. Cannot tolerate zanubrutinib treatment, or have hypersensitivity reactions to any components of the study drug;

3. Significant cardiovascular disease, including:

1. Myocardial infarction within 6 months prior to screening;

2. Unstable angina pectoris occurring within 3 months prior to screening;

3. Clinically significant arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes);

4. QTc (corrected by Fridericia formula): >450ms in men, >470ms in women, or other ECG abnormalities, including history of second-degree type II atrioventricular (AV) block or third-degree AV block;

5. Any grade 3 or 4 heart disease as defined by the New York Heart Association (NYHA) functional class;

6. Echocardiography (ECHO) showing left ventricular ejection fraction (LVEF) ≤40% (AHA, 2022);

7. Uncontrolled hypertension at screening, manifested as systolic blood pressure ≥180 mmHg and diastolic blood pressure ≥110 mmHg on at least two consecutive blood pressure measurements;

4. Requires continuous treatment with strong or moderate CYP3A inhibitors/inducers. Patients are not eligible if they have taken strong or moderate CYP3A inhibitors/inducers within 7 days prior to the first dose of study drug (or have taken these drugs for less than 5 half-lives);

5. Hepatitis B virus (HBV-DNA) ≥ 1x10^3 copies/mL or HBV-DNA > 200 IU/mL or active hepatitis C virus (HCV), or human immunodeficiency virus (HIV) Serologically positive;

6. Obvious bleeding tendency, such as a history of stroke, intracranial hemorrhage within 6 months, or a history of surgery within 4 weeks;

7. Serious infectious diseases at the same time;

8. Refuse to take reliable contraceptive methods during pregnancy, lactation or appropriate age;

9. Participate in another clinical trial of lymphoma treatment at the same time;

10. Unsuitable for enrollment by the investigator.