Orelabrutinib Combined With Rituximab Versus R-CVP in the Untreated MZL： A Randomized, Open Phase II Trial
- Conditions
- Interventions
- Registration Number
- NCT06700798
- Lead Sponsor
- Fei Li
- Brief 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
- Detailed Description
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 go...
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 90
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.
- Patients with central nervous system involvement;
- History or concurrent other untreated malignant tumors, except for cured basal cell carcinoma of the skin, cervical carcinoma in situ, and superficial bladder cancer;
- 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%;
- 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;
- 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;
- Known hereditary or acquired bleeding and thrombotic tendencies (such as hemophilia, coagulation disorders, thrombocytopenia, hypersplenism, etc.);
- Major surgical procedures or severe traumatic injuries, fractures, or ulcers within 4 weeks prior to enrollment;
- Factors that significantly affect the absorption of oral medications, such as inability to swallow, chronic diarrhea, and intestinal obstruction;
- Active infections requiring antimicrobial treatment (e.g., requiring antibacterial, antiviral drugs, excluding chronic hepatitis B antiviral treatment, antifungal treatment);
- 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);
- History of substance abuse and inability to quit or mental disorders;
- Participation in other anticancer drug clinical trials within 4 weeks prior to enrollment;
- 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;
- Pregnant or breastfeeding women; patients of childbearing potential who are unwilling or unable to use effective contraceptive measures;
- Other situations judged by the investigator that may affect the conduct of the clinical study and the determination of study results.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description OR-R rituximab Orelabrutinib 150mg, oral, once daily, Days 1-28, with a cycle of 4 weeks; Cycles 1-24； Rituximab: 375mg/m\^2, intravenous, Day 1, with a cycle of 4 weeks; Cycles 1-6 OR-R Orelabrutinib Orelabrutinib 150mg, oral, once daily, Days 1-28, with a cycle of 4 weeks; Cycles 1-24； Rituximab: 375mg/m\^2, intravenous, Day 1, with a cycle of 4 weeks; Cycles 1-6 R-CVP rituximab Rituximab: 375mg/m\^2, intravenous, Day 1, with a cycle of 3 weeks; Cycles 1-8； Cyclophosphamide: 750mg/m\^2, intravenous, Day 1, with a cycle of 3 weeks;Cycles 1-8； Vincristine: 1.4mg/m\^2 (maximum 2mg), intravenous, Day 1, with a cycle of 3 weeks;Cycles 1-8； Prednisone: 60mg/m\^2, oral, Days 1-5, with a cycle of 3 weeks，Cycles 1-8 Subsequently, maintenance with rituximab monotherapy until two years from the start of treatment or until toxicity intolerable. R-CVP Cyclophosphamide Rituximab: 375mg/m\^2, intravenous, Day 1, with a cycle of 3 weeks; Cycles 1-8； Cyclophosphamide: 750mg/m\^2, intravenous, Day 1, with a cycle of 3 weeks;Cycles 1-8； Vincristine: 1.4mg/m\^2 (maximum 2mg), intravenous, Day 1, with a cycle of 3 weeks;Cycles 1-8； Prednisone: 60mg/m\^2, oral, Days 1-5, with a cycle of 3 weeks，Cycles 1-8 Subsequently, maintenance with rituximab monotherapy until two years from the start of treatment or until toxicity intolerable. R-CVP Vincristine Rituximab: 375mg/m\^2, intravenous, Day 1, with a cycle of 3 weeks; Cycles 1-8； Cyclophosphamide: 750mg/m\^2, intravenous, Day 1, with a cycle of 3 weeks;Cycles 1-8； Vincristine: 1.4mg/m\^2 (maximum 2mg), intravenous, Day 1, with a cycle of 3 weeks;Cycles 1-8； Prednisone: 60mg/m\^2, oral, Days 1-5, with a cycle of 3 weeks，Cycles 1-8 Subsequently, maintenance with rituximab monotherapy until two years from the start of treatment or until toxicity intolerable. R-CVP Prednisone tablet Rituximab: 375mg/m\^2, intravenous, Day 1, with a cycle of 3 weeks; Cycles 1-8； Cyclophosphamide: 750mg/m\^2, intravenous, Day 1, with a cycle of 3 weeks;Cycles 1-8； Vincristine: 1.4mg/m\^2 (maximum 2mg), intravenous, Day 1, with a cycle of 3 weeks;Cycles 1-8； Prednisone: 60mg/m\^2, oral, Days 1-5, with a cycle of 3 weeks，Cycles 1-8 Subsequently, maintenance with rituximab monotherapy until two years from the start of treatment or until toxicity intolerable.
- Primary Outcome Measures
Name Time Method CRR up to two years The proportion of patients who achieve Complete Remission (CR) at the end of the combined antitumor treatment
- Secondary Outcome Measures
Name Time Method ORR up to two years ORR is defined as the percentage of participants with partial or complete response
PFS rate at 24month Two years after the last patient was enrolled. the proportion of patients who have not experienced disease progression or death due to any cause within 2 years of receiving the first dose of the study medication.
Safety parameters up to 3 years Type, frequency, and severity of AEs
Trial Locations
- Locations (1)
The First Affiliated Hospital of Nanchang University
🇨🇳Nanchang, Jiangxi, China