A Phase I Clinical Trial of Anti-CD19 Chimeric Antigen Receptor With Synthetic Biology Optimizing Nano-vector T Cells Injection for Subjects With Relapsed/Refractory/High-risk B-cell Lymphoma and B-cell Acute Lymphoblastic Leukemia
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Number of Participants with severe cytokine release syndrome(CRS) as a Measure of Safety and Tolerability.
研究概览
简要总结
The primary objective of this study is to evaluate the safety and clinical activity of anti-CD19 Chimeric Antigen Receptor T cells (KD-019 CAR-T)infusion in the treatment of relapsed/refractory B-cell Lymphoma and B-cell acute lymphoblastic leukemia （B-ALL）.
详细描述
The investigators designed an KD-019 Chimeric Antigen Receptor(CAR) with FMC63 single-chain antibody fragment (Scfv). This CAR has a CD8 hinge and transmembrane domains and a 4-1BB costimulatory domain; T cells expressing this CAR release relatively low levels of cytokines. Subjects with relapsed/refractory CD19-positive B-cell Lymphoma and B-ALL can participate if all eligibility criteria are met. Subjects receive chemotherapy prior to the infusion of KD-019 CAR-T cells. After the infusion, subjects will accept follow-up for side effects and effect of KD-019 CAR-T cells by the sponsor. Study procedures may be performed while hospitalized.
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
- •Patients or their legal guardians voluntarily participate and sign the Informed Consent Document;
- •18 Years and older, Male and female;
- •Pathologically and histologically confirmed CD19 + B cell tumors; Patients currently have no effective treatment options, such as chemotherapy or relapse after hematopoietic stem cell transplantation; Or patients voluntarily choose transfusion of anti-CD19 CAR-T cells as the first treatment program;
- •B-cell tumors / lymphomas and B-cell acute lymphoblastic leukemia include the following four types:
- •B-cell acute lymphoblastic leukemia;
- •Indolent B-cell lymphomas;
- •Aggressive B-cell lymphoma; 4、 Subjects:
- •(1) Residual lesions remain after treatment; (2) Not suitable for Hematopoietic stem cell transplantation (auto/allo-HSCT); (3) Relapse after Complement receptor 1 (CR1) and unsuitable for HSCT; (4) Patients with high risk factors; (5) Relapse or no remission after hematopoietic stem cell transplantation or cell immunotherapy.
- •5、 Have measurable or evaluable tumor foci; 6、 Liver, kidney and cardiopulmonary functions meet the following requirements:
- •Serum glutamic pyruvic transaminase (ALT) and serum glutamic oxaloacetic transaminase (AST) <3 ×upper limit of normal (ULN);
- •Total bilirubin ≤34.2μmol/L;
- •Serum creatinine<220μmol/L;
- •Baseline oxygen saturation≥95%;
- •Left ventricular ejection fraction（LVEF）≥40%. 7、 Subjects who did not receive Chemotherapy, Radiotherapy, Immunotherapy (immunosuppressive drugs) or other treatment within 4 weeks prior to enrollment; Relevant toxicity≤1 grade before enrollment (except for low toxicity such as hair loss); 8、Peripheral superficial venous blood flow is smooth, which can meet the needs of intravenous drip; 9、Clinical performance status of eastern cancer cooperation group (ECOG) score ≤2，Expected survival≥3 months;
排除标准
- •Pregnant (urine/blood pregnancy test positive) or lactating women;
- •Planned pregnancy during treatment or within 1 year after treatment, or a male subject whose partner plans pregnancy within 1 year of their cell transfusion;
- •Patients cannot guarantee effective contraception (condom or contraceptives, etc.) within 1 year after enrollment;
- •Active or uncontrollable infection within four weeks prior to enrollment;
- •Patients with active hepatitis B/C;
- •HIV-infected patients;
- •Severe autoimmune or immunodeficiency disorders;
- •Patients are allergic to macromolecule drugs such as antigens or cytokines;
- •Subjects participated in other clinical trials within 6 weeks before enrollment;
- •Systematic use of hormones within 4 weeks prior to enrollment (except for inhaled hormones);
- •Mental illness;
- •Drug abuse/addiction;
- •The investigators consider other conditions unsuitable for enrollment.
研究组 & 干预措施
Anti-CD19 CAR-T Cells Injection
Dosage form：injection Dosage:1-5x10^6/kg, 70ml/time, The CAR-T cells will be administered by i.v. injection over 20-30 minutes Frequency: total one time
干预措施: Anti-CD19 CAR-T Cells Injection (Biological)
结局指标
主要结局
Number of Participants with severe cytokine release syndrome(CRS) as a Measure of Safety and Tolerability.
时间窗: 0 to 14 days post infusion
The severe CRS post KD-019 CAR-T cells treatment will be evaluated and the maximum tolerated dose will be determined.
Copies numbers of CAR in peripheral blood (PB)
时间窗: 1 year post infusion
Copies numbers of CAR in peripheral blood (PB)
次要结局
- Overall survival(2 years post infusion)
- Duration of Response after administration(2 years post infusion)
- Progress Free Survival after administration(2 years post infusion)