Clinical Study of the Efficacy and Safety of XPO-1 Inhibitors in Combination With CAR-T Cells in Relapsed Refractory B-cell Non-Hodgkin's Lymphoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Duration of Response(DOR) Duration of Response(DOR)
研究概览
简要总结
Aim of this study will evaluate the Efficacy and Safety of XPO-1 inhibitors in combination with CAR-T cells in relapsed refractory B-cell non-Hodgkin's lymphoma
详细描述
B-cell non-Hodgkin's lymphoma (B-NHL) is the most common hematological malignancy originating from lymphohematopoietic tissue. Lymphoma is now one of the most rapidly growing malignancies worldwide, with approximately 350,000 new cases and over 200,000 deaths worldwide each year.With the use of rituximab in combination with standard chemotherapy regimens, progression-free survival (PFS) and overall survival (OS) in B-NHL have improved significantly, yet primary resistance or relapse progression still occurs in 40%-50% of B-NHL patients.The most widely used CAR-T therapy for R/R B-NHL in clinical practice is CAR-T therapy targeting CD19, which has a complete remission rate (CR) of 40%-53% and an overall remission rate (ORR) of 52%-82%.XPO1 inhibitors are potential drugs to enhance the anti-lymphoma effect of CD19 CAR-T cells, this study will evaluate the efficacy and safety of XPO-1 inhibitors in combination with CAR-T cells in relapsed refractory B-cell non-Hodgkin's lymphoma.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years.
- •Pathological immunohistochemistry or flow cytometry confirmed that R/ R B-cell Non-Hodgkin's Lymphoma with measurable (diameter greater than 1.5cm) lesions meets any of the following conditions: 1> After 4 courses of standard first-line therapy or 2 courses of more than two-line therapy, the lesions were reduced by <50%; 2> R/ R B-cell Non-Hodgkin's Lymphoma with disease progression after first-line or induction therapy; 3> After hematopoietic stem cell transplantation, new lesions appear or the size of previously affected lesions increased by more than 50%.
- •Previously treated with 2 or more lines of therapy.
- •The main organ functions need to meet the following conditions:LVEF≥50%;CR≤132 umol/l or CCr≥60 ml/min; ALT and AST≤2.5 times normal range#TB≤2 times ULN#Lung function≤Level 1; dyspnea(CTCAE v5.0),and blood oxygen saturation without oxygen absorption> 90%.
- •Pass the T-cell amplification test.
- •Voluntary tissue puncture/biopsy for tumor tissue retrieval before and after treatment.
- •Subjects of child-bearing or child-fathering potential must be willing to practice birth control from the time of enrollment on this study until the follow-up one year period of the study.
- •Estimated survival time ≥3 months.
- •Voluntary signing of informed consent and good compliance.
排除标准
- •Have used immunosuppressants or hormones within 2 weeks prior to signing informed consent, or plan to have to use immunosuppressants or high-dose hormones (e.g. prednisone >15mg) after signing informed consent, specifically systemic treatment, excluding treatment with topical or inhaled corticosteroids.
- •The presence of bacterial, fungal, viral, mycoplasma or other types of infection that, in the judgment of the investigator, are difficult to control.
- •Active hepatitis B or active hepatitis C.
- •HIV infection.
- •Active acute or chronic graft-versus-host disease (GVHD) at the time of signing the informed consent form.
- •Participated in an investigational clinical trial of any other drug within 30 days prior to signing the informed consent form.
- •Received CAR-T cell therapy within 3 months prior to signing the informed consent form.
- •Received an allogeneic hematopoietic stem cell transplant within 6 months prior to signing the informed consent form.
- •Presence of contraindications to XPO-1 inhibitor.
- •Prior malignancy (other than Relapsed Refractory B-cell Non-Hodgkin's Lymphoma), except for cured malignant tumors with no active lesions for 3 years;Adequate treatment of inactive lesions in non-melanoma skin cancer,malignant tonsilloma or carcinoma in situ.
- •Pregnant or breasting-feeding women.
- •Conditions deemed by the researcher to be inappropriate for participation in this clinical trial.
研究组 & 干预措施
XPO-1 Inhibitor+CAR-T Cells
XPO-1 Inhibitor plus CAR-T Cells
干预措施: Flu (Drug)
XPO-1 Inhibitor+CAR-T Cells
XPO-1 Inhibitor plus CAR-T Cells
干预措施: CTX (Drug)
XPO-1 Inhibitor+CAR-T Cells
XPO-1 Inhibitor plus CAR-T Cells
干预措施: CAR-T (Drug)
XPO-1 Inhibitor+CAR-T Cells
XPO-1 Inhibitor plus CAR-T Cells
干预措施: Selinexor (Drug)
结局指标
主要结局
Duration of Response(DOR) Duration of Response(DOR)
时间窗: up to 12 months
Duration of overall response will be assessed from the first XPO-1 Inhibitor Plus CAR-T cells given to progression,death or last follow-up.
Overall Response Rate (ORR)
时间窗: up to 12 months
To measure the duration of response to XPO-1 Inhibitor Plus CAR-T Cells over a follow-up period of 12 months
Adverse events profile
时间窗: up to 12 months
Number of participants with adverse events. Frequencies of toxicities based on the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 will be tabulated.
次要结局
- Complete Response Rate(up to 12 months)
- Time to Peak Amplification(Measured from start of treatment until 28 days after last dose)
- AUC0-28(Measured from start of treatment until 28 days after last dose)
- Progression-free Survival(up to 12 months)
- Overall Survival(up to 12 months)
- Peak Plasma Concentration(Measured from start of treatment until 28 days after last dose)