A Phase II Randomized, Controlled Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of HMPL-760 Plus R-GemOx Versus Placebo Plus R-GemOx in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma(R/R DLBCL)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- Hutchmed
- 入组人数
- 61
- 试验地点
- 16
- 主要终点
- Progression-free survival (PFS)
研究概览
简要总结
The goal of this study is to evaluate the efficacy of HMPL-760 in combination with R-GemOx versus placebo in combination with R-GemOx in patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma (R/R DLBCL).
详细描述
A Phase II Randomized, Controlled Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of HMPL-760 in Combination with R-GemOx versus Placebo in Combination with R-GemOx in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma (R/R DLBCL). The study phases include screening period, treatment period, safety observation period, PFS follow-up period, and OS follow-up period.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Sign the Informed consent form(ICF) and be able to follow the requirements of study protocol;
- •Age ≥18 years;
- •Eastern Cooperative Oncology Group (ECOG) performance status between 0 and 2;
- •Histopathologically confirmed diagnosis of DLBCL;
- •The investigator judges that the patient's current condition requires further treatment;
- •Patients should have at least one bi-dimensionally measurable lesion;
- •Expected survival is more than 12 weeks;
排除标准
- •Patients with known primary or secondary central nervous system lymphoma (CNSL) or the presence of clinical symptoms suggestive of CNSL;
- •Women who are pregnant (positive pregnancy test during the screening period) or breastfeeding;
- •Organ insufficiency;
- •Currently known history of liver disease, including cirrhosis, alcoholic liver, known active infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV):
- •History of significant organ bleeding, including gastrointestinal bleeding, hematencephalon, haemoptysis, etc., within 8 weeks prior to the first dose of study drug;
- •Known risk of bleeding, such as coagulation factor deficiency, vascular hemophilia; or the patient is receiving vitamin K antagonist (warfarin);
- •Toxicities from prior anticancer therapy not resolved to Grade ≤ 1 (except for alopecia and decreased appetite);
- •Clinically significant active infection;
研究组 & 干预措施
Group A: HMPL-760 planned dose 1 once daily (QD) in combination with R-GemOx regimen
Group A: Patients will receive HMPL-760 planned dose 1 once daily (QD) orally from Cycle 1 Day 1 until disease progression(PD), patient death, intolerable toxicity, etc., in combination with R-GemOx regimen in 21-day cycle for a total of 6 cycles. Rituximab 375 mg/m^2 ivgtt is given on day 1 of each cycle, and gemcitabine 1000 mg/m^2 ivgtt is given, followed by oxaliplatin 100 mg/m^2 ivgtt on day 2 of each cycle.
干预措施: HMPL-760 planned dose 1 (Drug)
Group A: HMPL-760 planned dose 1 once daily (QD) in combination with R-GemOx regimen
Group A: Patients will receive HMPL-760 planned dose 1 once daily (QD) orally from Cycle 1 Day 1 until disease progression(PD), patient death, intolerable toxicity, etc., in combination with R-GemOx regimen in 21-day cycle for a total of 6 cycles. Rituximab 375 mg/m^2 ivgtt is given on day 1 of each cycle, and gemcitabine 1000 mg/m^2 ivgtt is given, followed by oxaliplatin 100 mg/m^2 ivgtt on day 2 of each cycle.
干预措施: R-GemOx (Drug)
Group B: HMPL-760 placebo planned dose 1 once daily (QD) in combination with R-GemOx regimen
Patients will receive HMPL-760 placebo planned dose 1 once daily (QD) orally from Cycle 1 Day 1 until disease progression(PD), patient death, intolerable toxicity, etc., in combination with R-GemOx regimen in 21-day cycle for a total of 6 cycles. Rituximab 375 mg/m^2 ivgtt is given on day 1 of each cycle, and gemcitabine 1000 mg/m^2 ivgtt is given, followed by oxaliplatin 100 mg/m^2 ivgtt on day 2 of each cycle.
干预措施: R-GemOx (Drug)
Group B: HMPL-760 placebo planned dose 1 once daily (QD) in combination with R-GemOx regimen
Patients will receive HMPL-760 placebo planned dose 1 once daily (QD) orally from Cycle 1 Day 1 until disease progression(PD), patient death, intolerable toxicity, etc., in combination with R-GemOx regimen in 21-day cycle for a total of 6 cycles. Rituximab 375 mg/m^2 ivgtt is given on day 1 of each cycle, and gemcitabine 1000 mg/m^2 ivgtt is given, followed by oxaliplatin 100 mg/m^2 ivgtt on day 2 of each cycle.
干预措施: HMPL-760 placebo planned dose 1 (Drug)
Group C: HMPL-760 planned dose 2 once daily (QD) in combination with R-GemOx regimen
Patients will receive HMPL-760 planned dose 2 once daily (QD) orally from Cycle 1 Day 1 until disease progression(PD), patient death, intolerable toxicity, etc., in combination with R-GemOx regimen in 21-day cycle for a total of 6 cycles. Rituximab 375 mg/m^2 ivgtt is given on day 1 of each cycle, and gemcitabine 1000 mg/m^2 ivgtt is given, followed by oxaliplatin 100 mg/m^2 ivgtt on day 2 of each cycle.
干预措施: R-GemOx (Drug)
Group C: HMPL-760 planned dose 2 once daily (QD) in combination with R-GemOx regimen
Patients will receive HMPL-760 planned dose 2 once daily (QD) orally from Cycle 1 Day 1 until disease progression(PD), patient death, intolerable toxicity, etc., in combination with R-GemOx regimen in 21-day cycle for a total of 6 cycles. Rituximab 375 mg/m^2 ivgtt is given on day 1 of each cycle, and gemcitabine 1000 mg/m^2 ivgtt is given, followed by oxaliplatin 100 mg/m^2 ivgtt on day 2 of each cycle.
干预措施: HMPL-760 planned dose 2 (Drug)
Group D: HMPL-760 placebo planned dose 2 once daily (QD) in combination with R-GemOx regimen
Patients will receive HMPL-760 placebo planned dose 2 once daily (QD) orally from Cycle 1 Day 1 until disease progression(PD), patient death, intolerable toxicity, etc., in combination with R-GemOx regimen in 21-day cycle for a total of 6 cycles. Rituximab 375 mg/m^2 ivgtt is given on day 1 of each cycle, and gemcitabine 1000 mg/m^2 ivgtt is given, followed by oxaliplatin 100 mg/m^2 ivgtt on day 2 of each cycle.
干预措施: R-GemOx (Drug)
Group D: HMPL-760 placebo planned dose 2 once daily (QD) in combination with R-GemOx regimen
Patients will receive HMPL-760 placebo planned dose 2 once daily (QD) orally from Cycle 1 Day 1 until disease progression(PD), patient death, intolerable toxicity, etc., in combination with R-GemOx regimen in 21-day cycle for a total of 6 cycles. Rituximab 375 mg/m^2 ivgtt is given on day 1 of each cycle, and gemcitabine 1000 mg/m^2 ivgtt is given, followed by oxaliplatin 100 mg/m^2 ivgtt on day 2 of each cycle.
干预措施: HMPL-760 placebo planned dose 2 (Drug)
结局指标
主要结局
Progression-free survival (PFS)
时间窗: Up to approximately 2 years
Progression-free survival (PFS): Efficacy is evaluated using the Lugano Efficacy Evaluation Criteria for Malignant Lymphoma (Cheson 2014).
次要结局
- Objective Response Rate (ORR)(Up to approximately 2 years)
- Complete response (CR) rate(Up to approximately 2 years)
- Duration of response (DoR)(Up to approximately 2 years)
- Clinical benefit rate (CBR)(Up to approximately 2 years)
- Time to response (TTR)(Up to approximately 2 years)
- Overall survival (OS)(Up to approximately 2 years)
- Safety Endpoints of adverse events(Up to approximately 2 years)
- Pharmacokinetic(PK) profile of HMPL-760 in combination with R-GemOx(At the end of Cycle 7 (each cycle is 21 days))