orelabrutinib combined with rituximab versus r-cvp in the untreated mzl： a randomized, open phase ii trial

Conditions: Marginal Zone Lymphoma(MZL)

Summary: this study is a randomized, open-label, multicenter, prospective clinical trial aimed at evaluating the efficacy and safety of orelabrutinib combined with rituximab for the previously untreat mzl

for patients with advanced-stage mzl who require treatment, immunochemotherapy is the standard therapy, including regimens such as br, r-chop, r-cvp, etc. the second-generation btk inhibitor, orelabrutinib, has shown promising efficacy in relapsed/refractory mzl, suggesting that a chemofree regimen combining orelabrutinib with rituximab could also achieve good clinical outcomes in first-line treatment of mzl. however, there is still a lack of prospective studies to confirm this. this study plans to compare the efficacy and safety of orelabrutinib combined with rituximab followed by maintenance therapy with orelabrutinib to the r-cvp regimen.

Eligibility criteria:
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 cell carcinoma of the skin, cervical carcinoma in situ, and superficial bladder cancer; 3. patients with the following cardiovascular diseases: grade ii or above myocardial ischemia or myocardial infarction, poorly controlled arrhythmias (including qtc interval for males ≥450 ms, for females ≥470 ms); class iii to iv heart failure according to nyha standards, or echocardiography indicating left ventricular ejection 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 anticoagulant therapy; 5. arterial/venous thrombotic events within 12 months prior to enrollment, such as cerebrovascular accidents (including transient ischemic attacks, cerebral hemorrhage, 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 as inability 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, antifungal treatment); 10. active hepatitis b (hbv dna ≥2000 iu/ml or 104 copies/ml) or hepatitis c (hepatitis c antibody positive, and hcv rna above the lower limit of detection of the analytical 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 to enrollment; 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 study participation; 14. pregnant or breastfeeding women; patients of childbearing potential who are unwilling or unable to use effective contraceptive measures; 15. other situations judged by the investigator that may affect the conduct of the clinical study and the determination of study results.

Keywords: orelabrutinib combined with rituximab versus r-cvp