A Multicenter, Open-label, Randomized Controlled Study of Orelabrutinib in Combination With Bendamustine and Rituximab Versus Bendamustine and Rituximab in the Treatment of Transplant-Ineligible, Intermediate- to High-Risk Mantle Cell Lymphoma (MCL)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 78
- 试验地点
- 1
- 主要终点
- Complete response rate
研究概览
简要总结
This multicenter, open-label, randomized controlled trial aims to evaluate the efficacy and safety of Orelabrutinib in combination with Bendamustine and Rituximab (OBR) versus Bendamustine and Rituximab (BR) in patients with intermediate- to high-risk mantle cell lymphoma (MCL) who are ineligible for transplantation. The primary objective is to assess the complete response (CR) rate during the induction phase, with secondary objectives including progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and safety. Exploratory analysis will investigate the correlation between tumor biomarkers and treatment efficacy.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosed with MCL (mantle cell lymphoma) through flow cytometry or histopathology, and has not received prior treatment.
- •Age > 18 years of age, both genders are eligible.
- •Ann Arbor stage II-IV; for stage II subjects, those who require systemic therapy based on the investigator's judgment are eligible.
- •At least one measurable lesion.
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0-
- •Any one of the following high-risk factors is present: MIPI score of 4-11, Ki67 > 50%, TP53 abnormality, blastic or pleomorphic variation.
- •Patients who are not suitable candidates for autologous hematopoietic stem cell transplantation.
- •Laboratory tests (blood routine, liver and kidney function) meet the following requirements: a) Blood routine: White blood cell count ≥3.0×10^9/L, absolute neutrophil count ≥1.5×10^9/L, hemoglobin ≥90g/L, platelet count ≥75×10^9/L. b) Liver function: Transaminases ≤2.5 times the upper limit of normal, bilirubin ≤1.5 times the upper limit of normal. c) Serum creatinine 44-133 mmol/L.
- •The investigator judges that the subject's life expectancy is greater than 12 weeks from the time of screening.
- •Willing and able to participate in all required assessments and procedures of the study protocol.
排除标准
- •Patients who have previously received treatment with BTK inhibitors.
- •Patients with severe complications or serious infections.
- •Patients with uncontrolled cardiovascular diseases, coagulation disorders, connective tissue diseases, serious infectious diseases, etc.
- •Patients with active infections requiring systemic treatment, including bacterial, fungal, and viral infections.
- •HIV-infected individuals.
- •Patients with mental disorders or those who are known or suspected to be unable to fully comply with the study protocol.
- •Patients whom the investigator judges to have other conditions that make them unsuitable for participation in this study.
研究组 & 干预措施
Orelabrutinib + Bendamustine + Rituximab (OBR)
In induction phase, patients will be randomized in two groups, one is OBR and another is BR. Patients in OBR group will receive rituximab 375 mg/m² IV on day 1, bendamustine 90 mg/m² IV on day 1 and 2, and orelabrutinib 150mg/day PO once daily, every 28 day per cycle for 6 cycles.
干预措施: Orelabrutinib (Drug)
Orelabrutinib + Bendamustine + Rituximab (OBR)
In induction phase, patients will be randomized in two groups, one is OBR and another is BR. Patients in OBR group will receive rituximab 375 mg/m² IV on day 1, bendamustine 90 mg/m² IV on day 1 and 2, and orelabrutinib 150mg/day PO once daily, every 28 day per cycle for 6 cycles.
干预措施: Bendamustine (Drug)
Orelabrutinib + Bendamustine + Rituximab (OBR)
In induction phase, patients will be randomized in two groups, one is OBR and another is BR. Patients in OBR group will receive rituximab 375 mg/m² IV on day 1, bendamustine 90 mg/m² IV on day 1 and 2, and orelabrutinib 150mg/day PO once daily, every 28 day per cycle for 6 cycles.
干预措施: Rituximab (Drug)
Bendamustine + Rituximab (BR)
In induction phase, patients will be randomized in two groups, one is OBR and another is BR. Patients in BR group will receive rituximab 375 mg/m² IV on day 1, bendamustine 90 mg/m² IV on day 1 and 2, every 28 day per cycle for 6 cycles.
干预措施: Bendamustine (Drug)
Bendamustine + Rituximab (BR)
In induction phase, patients will be randomized in two groups, one is OBR and another is BR. Patients in BR group will receive rituximab 375 mg/m² IV on day 1, bendamustine 90 mg/m² IV on day 1 and 2, every 28 day per cycle for 6 cycles.
干预措施: Rituximab (Drug)
Orelabrutinib + Venetoclax (OV)
In maintanance phase, patients will receive different medical regimen according to their TP53 mutation and blastic and pleomorphic variants status. Patients with TP53 mutation or blastic and/or pleomorphic variant will receive orelabrutinib 150mg/day PO once daily and venetoclax for up to 2 years, the dosing of Venetoclax is escalated gradually to reach a target dose of 400 mg.
干预措施: Orelabrutinib (Drug)
Orelabrutinib + Venetoclax (OV)
In maintanance phase, patients will receive different medical regimen according to their TP53 mutation and blastic and pleomorphic variants status. Patients with TP53 mutation or blastic and/or pleomorphic variant will receive orelabrutinib 150mg/day PO once daily and venetoclax for up to 2 years, the dosing of Venetoclax is escalated gradually to reach a target dose of 400 mg.
干预措施: Venetoclax (Drug)
Orelabrutinib (O)
In maintanance phase, patients will receive different medical regimen according to their TP53 mutation and blastic and pleomorphic variants status. Patients without TP53 mutation or blastic and/or pleomorphic variant will receive orelabrutinib 150mg/day PO once daily for up to 2 years.
干预措施: Orelabrutinib (Drug)
结局指标
主要结局
Complete response rate
时间窗: End of induction treatment visit (6-8 weeks after last dose on Day 1 of Cycle 6 [Cycle length=28 days]
Percentage of participants with complete response was determined on the basis of investigator assessments according to 2014 Lugano criteria.
次要结局
- Overall Response Rate(End of induction treatment visit (6-8 weeks after last dose on Day 1 of Cycle 6 [Cycle length=28 days])
- Overall survival(Baseline up to data cut-off (up to approximately 2 years))
- Progression-free survival(Baseline up to data cut-off (up to approximately 2 years))
研究者
Zhao Weili
First Deputy Director, Hematology Department
Ruijin Hospital