A Randomized, Open-Label Phase II Clinical Study of Orelabrutinib Combined With Rituximab Versus R-CVP in the Treatment of Newly Diagnosed Marginal Zone Lymphoma (MZL).
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- CRR
研究概览
简要总结
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
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
R-CVP
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.
干预措施: Cyclophosphamide (Drug)
R-CVP
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.
干预措施: Vincristine (Drug)
OR-R
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
干预措施: Orelabrutinib (Drug)
OR-R
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
干预措施: rituximab (Drug)
R-CVP
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.
干预措施: rituximab (Drug)
R-CVP
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.
干预措施: Prednisone tablet (Drug)
结局指标
主要结局
CRR
时间窗: up to two years
The proportion of patients who achieve Complete Remission (CR) at the end of the combined antitumor treatment
次要结局
- ORR(up to two years)
- PFS rate at 24month(Two years after the last patient was enrolled.)
- Safety parameters(up to 3 years)
研究者
Fei Li
Chief physician
The First Affiliated Hospital of Nanchang University