Orelabrutinib Combined With Rituximab Versus R-CVP in the Untreated MZL： A Randomized, Open Phase II Trial

Inclusion Criteria:

1.Age ≥18 years； 2.ECOG performance status level 0~2； 3.Life expectancy of at least 12 weeks; 4.Confirmed CD20-positive marginal zone lymphoma according to the WHO 2008 lymphoma classification criteria, including splenic MZL, nodal MZL, and extranodal MZL subtypes; 5.Measurable lesions detected by enhanced computed tomography (CT) or magnetic resonance imaging (MRI); 6.Indication for treatment according to NCCN guidelines and no prior systemic treatment for MZL; 7.Normal function of major organs; 8.Women of childbearing age must have taken reliable contraceptive measures or undergone a pregnancy test (serum or urine) within 7 days before enrollment, with a negative result, and must be willing to use appropriate contraceptive methods during the trial period and for 8 weeks after the last administration of the trial medication. For men, they must agree to use appropriate contraceptive methods during the trial period and for 8 weeks after the last administration of the trial medication or have undergone surgical sterilization; 9.The subject voluntarily participates in this study, signs the informed consent form, has good compliance, and cooperates with follow-up.

• Exclusion Criteria:

1. Patients with central nervous system involvement;

2. History or concurrent other untreated malignant tumors, except for cured basal cellcarcinoma of the skin, cervical carcinoma in situ, and superficial bladder cancer;

3. Patients with the following cardiovascular diseases: Grade II or above myocardialischemia or myocardial infarction, poorly controlled arrhythmias (including QTcinterval for males ≥450 ms, for females ≥470 ms); Class III to IV heart failureaccording to NYHA standards, or echocardiography indicating left ventricularejection fraction (LVEF) <50%;

4. Coagulation abnormalities (INR >1.5 or prothrombin time (PT) >ULN+4 seconds or APTT >1.5 ULN), with a tendency to bleed or undergoing thrombolytic or anticoagulanttherapy;

5. Arterial/venous thrombotic events within 12 months prior to enrollment, such ascerebrovascular accidents (including transient ischemic attacks, cerebralhemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism;

6. Known hereditary or acquired bleeding and thrombotic tendencies (such as hemophilia,coagulation disorders, thrombocytopenia, hypersplenism, etc.);

7. Major surgical procedures or severe traumatic injuries, fractures, or ulcers within 4 weeks prior to enrollment;

8. Factors that significantly affect the absorption of oral medications, such asinability to swallow, chronic diarrhea, and intestinal obstruction;

9. Active infections requiring antimicrobial treatment (e.g., requiring antibacterial,antiviral drugs, excluding chronic hepatitis B antiviral treatment, antifungaltreatment);

10. Active hepatitis B (HBV DNA ≥2000 IU/mL or 104 copies/mL) or hepatitis C (hepatitisC antibody positive, and HCV RNA above the lower limit of detection of theanalytical method);

11. History of substance abuse and inability to quit or mental disorders;

12. Participation in other anticancer drug clinical trials within 4 weeks prior toenrollment;

13. Received treatment with potent CYP3A4 inhibitors within 7 days prior to enrollment,or received treatment with potent CYP3A4 inducers within 12 days prior to studyparticipation;

14. Pregnant or breastfeeding women; patients of childbearing potential who areunwilling or unable to use effective contraceptive measures;

15. Other situations judged by the investigator that may affect the conduct of theclinical study and the determination of study results.