A Prospective, Phase II Clinical Study Protocol of Orelabrutinib Combined With Standard Immunochemotherapy With or Without Autologous Hematopoietic Stem Cell Transplantation (Auto-HSCT) for Newly Diagnosed Diffuse Large B-cell Lymphoma (DLBCL)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- 1 year Progression free survival (PFS)
研究概览
简要总结
This study is a prospective, open-label, multicenter study in previously untreated participants with CD20-positive DLBCL. Orelabrutinib combined with standard immunochemotherapy with or without autologous hematopoietic stem cell transplantation (auto-HSCT) for newly diagnosed diffuse large B-cell lymphoma (DLBCL). The primary objective is to explore the 1-year progression-free survival (PFS) of orelabrutinib combined with standard immunochemotherapy with or without auto-HSCT in newly diagnosed DLBCL.
详细描述
Diffuse large B-cell lymphoma (DLBCL), as the most common type of adult lymphoma, accounts for 35%-40% of non-Hodgkin lymphoma (NHL) and is characterized by high heterogeneity. This study is a prospective, open-label, multicenter study in previously untreated participants with CD20-positive DLBCL. In the induction phase, patients receive 4 cycles of orelabrutinib combined with standard chemotherapy. For transplant-eligible patients, based on response assessment after 4 cycles, those achieving PR or CR proceed to auto-HSCT, followed by either 6 cycles of orelabrutinib maintenance or no maintenance based on patient preference. For transplant-ineligible patients, based on response assessment after 4 cycles, those achieving PR or CR receive an additional 2-4 cycles of orelabrutinib combination therapy. Depending on the patient's performance status, each cycle lasts 21-28 days. The primary objective is to explore the 1-year progression-free survival (PFS) of orelabrutinib combined with standard immunochemotherapy with or without auto-HSCT in newly diagnosed DLBCL.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Signed informed consent;
- •Age 18-80 years at the time of signing informed consent, and willingness to comply with the study protocol procedures;
- •Pathologically confirmed CD20-positive DLBCL;
- •④ IPI score of 2-5;
- •⑤ ECOG performance status of 0-2;
- •⑥ Life expectancy ≥12 months;
- •⑦ Left ventricular ejection fraction (LVEF) ≥50% as assessed by multigated acquisition (MUGA) scan or echocardiography (ECHO);
- •Adequate hematologic function (unless due to underlying disease, e.g., extensive bone marrow involvement, or hypersplenism secondary to splenic involvement attributed to DLBCL as determined by the investigator; transfusion of blood products is permitted), defined as follows:
- •Hemoglobin ≥90 g/L within 7 days prior to enrollment without packed red blood cell transfusion;
- •Absolute neutrophil count (ANC) ≥1.0 × 10⁹/L;
- •Platelet count ≥75 × 10⁹/L.
- •⑨ Adequate organ function.
排除标准
- •Presence of uncontrolled cardiovascular or cerebrovascular disease, coagulation disorders, autoimmune diseases, severe infectious diseases, etc.;
- •Abnormal laboratory values at screening (unless attributable to lymphoma):
- •Coagulation function: INR > 1.5× the upper limit of normal (ULN); PT and APTT > 1.5× ULN;
- •Liver function: ALT or AST > 2× ULN; ALP and bilirubin > 1.5× ULN;
- •Renal function: Creatinine > 1.5× ULN; creatinine clearance < 60 mL/min (estimated by the Cockcroft-Gault formula);
- •③ HIV-infected patients;
- •④ For HBsAg-positive patients, HBV DNA must be negative prior to enrollment. In addition, if a patient is HBsAg-negative but HBcAb-positive (regardless of HBsAb status), HBV DNA testing is still required. If the result is positive, antiviral therapy is needed, and HBV DNA must be negative prior to enrollment;
- •⑤ Requiring continuous treatment with strong or moderate CYP3A inhibitors or CYP3A inducers. Patients who have taken strong or moderate CYP3A inhibitors or CYP3A inducers within 7 days prior to the first dose of study drug (or have not completed at least 5 half-lives since the last dose) are not eligible for enrollment;
- •Inability to swallow capsules or presence of gastrointestinal conditions that significantly affect gastrointestinal function, such as malabsorption syndrome, gastric or small bowel resection, symptomatic inflammatory bowel disease, or partial or complete intestinal obstruction;
- •Other concurrent and uncontrolled medical conditions that, in the investigator's opinion, may affect the patient's participation in the study, including patients with psychiatric disorders or other known or suspected inability to fully comply with the study protocol.
结局指标
主要结局
1 year Progression free survival (PFS)
时间窗: From date of signing the informed consent until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1 year
PFS is defined as the time from registration to the first occurrence of progression or relapse as assessed by the investigator, or death from any cause. PFS for patients without disease progression, relapse, or death will be censored at the time of the last tumor assessment.
次要结局
- The occurrence of adverse events and serious adverse events(At the end of whole theray (through study completion, an average of 1 year))
- ORR (Objective Response Rate)(At the end of Consolidation therapy (up to 8 cycles, each cycle is 21-28 days ))
- CRR (Complete Response Rate)(At the end of Consolidation therapy (up to 8 cycles, each cycle is 21-28 days))
- 2-year Progression free survival (PFS)(From date of signing the informed consent until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years)
- 2-year overall survival (OS)(From date of signing the informed consent until the date of death from any cause, whichever came first, assessed up to 2 years)