A Prospective Study of Integrated Radiotherapy-optimized ASCT Sequential CAR-T Therapy on the Efficacy and Safety of Patients With Relapsed and Refractory Aggressive B-cell Non-Hodgkin Lymphoma.
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Complete remission rate(CRR)
研究概览
简要总结
This study aims to investigate a novel therapeutic strategy of integrated radiotherapy before autologous stem cell transplantation (ASCT) sequential chimeric antigen receptor T-cell(CAR-T) therapy for patients with relapsed/refractory(R/R) aggressive B-cell non-Hodgkin lymphoma (B-NHL). By evaluating the efficacy and safety of this multimodal approach, we seek to provide a theoretical foundation and clinical data to optimize outcomes for relapsed/refractory aggressive B-NHL patients.
详细描述
This trial will enroll R/R aggressive B-NHL patients aged ≥18 years who have undergone at least two prior lines of systemic therapy. Participants will be stratified into two cohorts based on post-salvage therapy disease status:
Cohort 1 (PET/CT-, ctDNA+): Patients will receive low-dose radiotherapy (RT) combined with reduced-intensity SEAM/TB chemotherapy as a conditioning regimen, followed by ASCT and sequential CAR-T therapy.
Cohort 2 (PET/CT+, ctDNA+): Patients will receive high-dose RT combined with reduced-intensity SEAM/TB chemotherapy as a conditioning regimen, followed by ASCT and sequential CAR-T therapy.
All patients completing the combined ASCT-CAR-T protocol will undergo longitudinal follow-up for safety, efficacy survival outcomes .
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Single (Investigator)
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
- •Age ≥18 years.
- •Histologically confirmed aggressive B-NHL.
- •Life expectancy >3 months.
- •Appropriate organ function:
- •Cardiac function: cardiac ejection fraction ≥50%; Liver function: alanine aminotransferase and glutamic aminotransferase ≤ 2 times the upper limit of normal values; renal function: serum creatinine clearance ≥80 mL/min; serum creatinine <160 mmol/L Lung function: SPO2>91% without oxygen intake
- •Adequate bone marrow reserve defined as:
- •hemoglobin ≥90 g/L. platelet count ≥70 x 10^9/L. absolute neutrophil count ≥1.5 x 10^9/L.
- •The patient is capable of understanding and willing to provide written informed consent.
- •Subjects of childbearing or childbearing potential must be willing to practice birth control from the date of enrollment in this study until study follow-up.
排除标准
- •severe hepatic and renal function abnormalities (alanine aminotransferase, bilirubin, creatinine > 2 times the upper limit of normal);
- •Presence of organic heart disease with resulting clinical symptoms or abnormal cardiac function (NYHA cardiac function classification ≥ grade 2);
- •ECG QTc interval >500 ms;
- •active hepatitis B/hepatitis C;
- •uncontrolled active infection;
- •human immunodeficiency virus infection;
- •concurrent other tumors requiring treatment or intervention;
- •current or anticipated need for systemic corticosteroid therapy;
- •pregnant or lactating women;
- •abandonment of consolidation autologous hematopoietic stem cell transplantation for financial reasons;
- •other psychological conditions that prevent the patient from participating in the study or signing the informed consent form;
- •Subjects who, in the judgment of the investigator, are unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or do not meet the requirements for participation in the study.
结局指标
主要结局
Complete remission rate(CRR)
时间窗: At the end of 3 months after CAR-T infusion
The rate of patients who achieved CR 3 months after CAR-T infusion
次要结局
- Major adverse reactions(From enrollment to 1 month after CAR-T infusion of last patient)
- Time to bone marrow hematopoietic reconstitution(From enrollment to 3 months after stem cell infusion of last patient)
- 2-year progression-free survival(PFS)(From enrollment to 2-year after the end of last patient's treatment)
- 2-year overall survival(OS)(From enrollment to 2-year after the end of last patient's treatment)