Exploratory Clinical Study of CD19-targeted CAR-T and CAR-DC in the Treatment of Relapsed and Refractory B-cell Lymphoma
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 70
- 试验地点
- 1
- 主要终点
- MTD
研究概览
简要总结
This is an open, single-arm, prospective, dose-escalation clinical trial designed to evaluate the safety and the preliminary efficacy of CD19-targeted CAR-T combined with CAR-DC in the treatment of relapsed and refractory B-cell lymphoma
详细描述
6-18 patients are planned to be enrolled in the dose-escalation trial. The dose of CD19-CAR-DC was according to the 3+3 dose-escalation principle (0.25×10^6/kg, 0.5×10^6/kg, 0.75×10^6/kg ( ±20%) . CAR-T was 2×10^6/kg . The primary endpoints are DLT, MTD, and the second endpionts are the overall response rates (CR and PR), overall survival, and progression-free survival. Based on the results in the dose-escalation trial, the recommended dose will be determined. Another 52 patients will be enrolled to continue estimating the safety and efficacy.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female participants aged 18 to 75 years old at the time enrollment, with ECOG Score of ≤ 3;
- •Patients should provide a written informed consent;
- •Histologically confirmed CD19+ DLBCL, HGBL-DHL, MCL, tFL, PMBL;
- •Confirmation obtained from central pathology review before enrollment;
- •Sufficient formalin-fixed, paraffin-embedded tumor samples were required for histologically confirmed diagnosis and detection of CD19 expression;
- •Relapsed DLBCL and tFL after ≥2 lines of chemotherapy that include rituximab and anthracycline, or refractory disease as defined in the SCHOLAR-1 study: progressive disease after receiving ≥ 4 cycles of first-line therapy or stable disease (received 2 cycles of later-line therapy) as best response to chemotherapy or relapse ≤ 12 months after autologous stem cell transplantation (ASCT);
- •Relapsed/refractory MCL after ≥ 2 lines of prior therapy, including immunochemotheapy and BTK inhibitor such as ibrutinib, or patient did not agree to receive BTK inhibitor treatment;
- •At least one measurable tumor according to revised International Working Group (IWG) Response criteria;
- •Life expectancy ≥ 3 months;
- •Adequate cardiac, pulmonary, liver, renal, and bone marrow functions, with the following laboratory values: an absolute neutrophil count > 1,000/mm3, platelets count ≥ 45,000/mm3, and hemoglobin > 8.0g/dl; alanine aminotransferase and aspartate aminotransferase ≤ 2.5 × the upper limit of the normal range (ULN), and total bilirubin ≤ 2.0 mg/dl; a serum creatinine of ≤ 1.5 × ULN; a left ventricular ejection fraction ≥ 50%;
排除标准
- •Prior treatment that included anti-CD19-targeted therapy, CAR T cell therapy, gene therapy, and allogenic hematopoietic stem cell transplantation (allo-HSCT);
- •Chemotherapy other than lymphodepleting chemotherapy, therapeutic doses of steroids, immunosuppressive agent, any radiation therapy or anti-tumor targeted therapy including lenalidomide, bortezomib, ibrutinib, received within 2 weeks before cell collection;
- •Clinical trial with investigational drug was performed within 4 weeks;
- •History of other cancers;
- •Active hepatitis B or hepatitis C. Hepatitis B: HBV-DNA ≥ 1,000 IU/ml; Hepatitis C: HCV RNA positive;
- •HIV infection;
- •Uncontrollable infection of active bacteria and fungi;
- •Currently pregnant or refusal to practice birth control within 1 year;
- •Active autoimmune or inflammatory diseases;
- •Central nervous system lymphoma.
结局指标
主要结局
MTD
时间窗: Up to 28 days
MTD was the highest dose for DLT in ≤1/6 subjects
Incidence of abnormalities
时间窗: Up to 28 days
Incidence of abnormalities in AE/SAE/AESI/laboratory tests/electrocardiograms/vital signs.
DLT
时间窗: Up to 28 days
To evaluate the safety, tolerability, and determine the recommended dosage of combined therapy of CD19 CAR-T and CD19 CAR-DC for Relapsed/Refractory B-cell Non-Hodgkin Lymphoma
次要结局
- Overall Response Rate(Up to 2 years)
- Duration of Response(Up to 2 years)
- Progression Free Survival(Up to 2 years)