The Efficacy and Safety of Pola-ZR2 (Polatuzumab Vedotin, Zanubrutinib, Rituximab and Lenalidomide) Versus ZR2 (Zanubrutinib, Rituximab and Lenalidomide) in the Treatment of Old Patients With de Novo Diffuse Large B-cell Lymphoma: A Multicenter, Prospective, Randomized, Open-label, Controlled Trial
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- 2-year PFS rate
研究概览
简要总结
A multicenter, prospective, randomized, open-label, controlled trial to evaluate the efficacy and safety of Pola-ZR2 (polatuzumab vedotin, zanubrutinib, rituximab and lenalidomide) versus ZR2 (zanubrutinib, rituximab and lenalidomide) in the treatment of old patients with de novo diffuse large B-cell lymphoma
详细描述
This study will evaluate the efficacy and safety of Pola-ZR2 versus ZR2 in the treatment of elderly de novo diffuse large B-cell lymphoma patients. Subjects will be randomly assigned 1:1 to Pola-ZR2 or ZR2 regimen. The stratification will be performed according to international prognostic index (2-3 / 4-5).
Patients in Pola-ZR2 group will receive 6 cycles of polatuzumab vedotin 1.8 mg/kg, day 2 on the 1st cycle and day 1 on the 2nd to 6th cycle, zanubrutinib 160mg bid, day 1-21, orally, lenalidomide 25mg qd, day 2-11, orally, rituximab 375mg/m², day 1, intravenously, every 21 days. Patients in ZR2 group will receive 6 cycles of zanubrutinib 160mg bid, day 1-21, orally, lenalidomide 25mg qd, day 2-11, orally, rituximab 375mg/m², day 1, intravenously, every 21 days.
Patients who receive complete response or partial response after induction therapy will receive lenalidomide 25 mg qd po during 1-10 days in every 21 days for 2 years.
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
- 70 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must satisfy all of the following criteria to be enrolled in the study:
- •Histologically-confirmed diffuse large B-cell lymphoma (without central nervous system involvement)
- •Aged ≥ 80 years old or aged 70-79 with comprehensive geriatric assessment stratified as unfit or frail
- •International prognostic index score 2 to 5
- •At least 1 measurable site of disease (defined as lymph nodes with the long diameters longer than 1.5cm, or extra-nodal sites with the long diameters longer than 1.0cm; meanwhile, any lesion site with at least 2 measurable vertical diameters)
- •Able to swallow capsules
- •Life expectancy of at least 3 months determined by researchers
- •The patient or his or her legal representative must provide written informed consent prior to any special examination or procedure for the research.
- •Anti-lymphoma drugs have not been used before (except glucocorticoids)
排除标准
- •Presence of any of the following criteria will exclude a patient from enrollment:
- •Uncontrolled blood clotting disorders, connective tissue diseases, serious infectious diseases and other diseases
- •Laboratory measures meet the following criteria at screening (unless caused by lymphoma):
- •Neutrophils<1.5×10^9/L Platelets<80×10^9/L ALT or AST is 2 times higher than the upper limits of normal (ULN), serum bilirubin are 1.5 times higher than the ULN.
- •Creatinine is 1.5 times higher than the ULN or eGFR is lower than 40ml/min/1.73m^2 (according to Cockcroft-Gault Equation or MDRD Equation).
- •uncontrollable or significant cardiovascular diseases, including but not limited to: Left ventricular ejection fraction<50% Cardiomyopathy, such as dilated cardiomyopathy, hypertrophic cardiomyopathy, restrictive cardiomyopathy QTc prolongation with clinical significance, QTc interval>470ms (females) or 480ms (males), type 2 second-degree atrioventricular block or third-degree atrioventricular block
- •Patients with HbsAg positive are required to have HBV DNA<1.0×10^3 IU/ml before entering the group. In addition, if the patient is HBsAg negative but HBcAb positive (regardless of HBsAb status), HBV DNA test is also required, and HBV DNA<1.0×10^3 IU/ml is required before entering the group
- •Patients with psychiatric disorders or patients who are known or suspected to be unable to fully comply with the study protocol
- •HIV-infected patients
- •History of stroke or intracranial hemorrhage within 6 months prior to start of therapy
- •Other medical conditions determined by the researchers that may affect the study
研究组 & 干预措施
Pola-ZR2
six courses of polatuzumab vedotin, zanubrutinib, rituximab and lenalidomide induction therapy and lenalidomide maintenance therapy
干预措施: polatuzumab vedotin, zanubrutinib, rituximab and lenalidomide (Drug)
ZR2
six courses of zanubrutinib, rituximab and lenalidomide induction therapy and lenalidomide maintenance therapy
干预措施: zanubrutinib, rituximab and lenalidomide (Drug)
结局指标
主要结局
2-year PFS rate
时间窗: up to approximately 2 years
次要结局
- Progression free survival(Baseline up to data cut-off (up to approximately 2 years))
- 2-year OS rate(Baseline up to data cut-off (up to approximately 2 years))
- Overall response rate(End of treatment visit (6-8 weeks after last dose on Day 1 of Cycle 6 [Cycle length=21 days]])
- Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0(From enrollment to study completion, a maximum of 5 years)
- Percentage of Participants Achieving Meaningful Improvement in European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 Questionnaire (EORTC QLQ-C30)(Day 1 of Cycles 1 and 4 (Cycle length=21 days); 30 days after treatment completion)
- Percentage of Participants Achieving Meaningful Improvement in EORTC QLQ-ELD14 (Elderly Module)(Day 1 of Cycles 1 and 4 (Cycle length=21 days); 30 days after treatment completion)
- Overall survival(Baseline up to data cut-off (up to approximately 2 years))
- Complete response rate(End of treatment visit (6-8 weeks after last dose on Day 1 of Cycle 6 [Cycle length=21 days]])
- Percentage of Participants Achieving Meaningful Improvement in Functional Assessment of Cancer Therapy-Lymphoma Lymphoma Subscale (FACT-Lym LymS)(Day 1 of Cycles 1 and 4 (Cycle length=21 days); 30 days after treatment completion)
研究者
Zhao Weili
Professor and Director, Shanghai Institute of Hematology
Ruijin Hospital