Anti-CD19:TCRζ Chimeric Antigen Receptor-T Cells in the Treatment for Chemotherapy-resistant or Refractory CD19+B Cell Lymphoma:a Double-arm, Single Center, Open-label Clinical Trial
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- overall survival
研究概览
简要总结
This study aims to evaluate the safety, efficacy and duration of response of CD19 Chimeric Antigen Receptor (CAR) redirected allogeneic T-cells in patients with chemotherapy-resistant or refractory CD19+ B cell lymphoma.
详细描述
This is a single-centre, randomised, open label Phase I clinical trial of CD19 Chimeric Antigen Receptor (CAR) T-cells (CD19 CAR T-cells) in patients with chemotherapy-resistant or refractory CD19+ B cell lymphoma. Following informed consent and registration to the trial, Patients will receive the allogeneic CD19 CAR T-cells following lymphodepleting chemotherapy. The study will evaluate the safety, efficacy and duration of response of the CD19 CAR T-cells in patients with chemotherapy-resistant or refractory CD19+ B cell lymphoma.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Enrollment for enough male or female patients with CD19+ hematological malignancies, without regimens for cure (autologous or allogeneic stem cell transplantation), and having a poor prognosis (several months to 2 years) under current optional regimens
- •Age ranges from 18 to 70 years old
- •Expected survival time longer than 12 weeks
- •Performance status score 0-2
- •Pathologically confirmed CD19+ lymphoma (CD19+ follicular lymphoma, Mantle cell lymphoma, diffuse large B cell lymphoma) and meets at least one of follows:
- •having received at least 2-4 cycles of combined chemotherapy (excluding monoclonal antibody monotherapy, such as rituximab) but do not reach a complete response; recurrent disease; not applicable for conventional stem cell transplantation; being partial responsible or stable but not complete responsible after the latest therapy
- •recurrence develops after stem cell transplantation
- •diagnosis confirmed but refusing to receive conventional therapy
- •Creatinine<2.5 mg/dl；
- •alanine aminotransferase/aspartate aminotransferase lower than 3 folds of normal range
- •Bilirubin<2.0 mg/dl；
- •Venous channel available and no contraindications for leukocyte collection
- •Reliable contraception from the beginning to 30 days after discontinuation of therapy
- •Informed consent signed
排除标准
- •Central nerve system invasion with symptoms
- •Other concurrent uncontrolled malignancies
- •Hepatitis B infection or active period of hepatitis C, HIV infection
- •Other uncontrolled diseases hampering the intervention in the study
- •Coronary heart disease, angina, myocardial infarction, arrhythmia, cerebral thrombosis, cerebral hemorrhage and other serious cardiovascular or cerebrovascular diseases.
- •Grade 2-3 or uncontrolled hypertension
- •History of uncontrolled mental disease
- •Not suitable for participation judged by researchers
- •Immunosuppressive agents administered due to organ transplantation, not including recent or current inhaled corticosteroid
- •Medical history of mental diseases or abnormities of lab tests might increase the risks of participation in study or drug administration, or interfering the results
- •Screening suggesting transfection efficiency of targeting cells lower than 30% or cell expansion deficiency under CD3/CD28 (cluster of differentiation 3,CD3)stimulation (less than 5 folds)
- •Unstable pulmonary embolism, deep venous thromboembolism or other major arterial/venous thromboembolism events develop in 30 days before the randomization. If anti-coagulation therapy is received, the treatment dose should reach stability before the randomization.
- •Pregnancy or lactation, or pregnancy planned during the study or in 2 months after the study
- •Reliable contraception not accepted during the study or in 2 months after the study. Female subjects are required to provide negative results from serum or urine pregnancy test 48 hours before therapy
- •Systematic active or uncontrolled infection (excluding infection of urinary tract or upper respiratory tract infection) in 14 days before the randomization
- •Informed consent not signed or study rules violated
研究组 & 干预措施
IL-2 pre-treated CD19 cells
Initial therapy: IL-2 (interleukin,IL)stimulated, CD28-ζ-vector (cluster of differentiation 28,CD28)transfected T cells(TCRζ chimeric antigen receptor-T cell)， were administered at 1×106/kg by single infusion
干预措施: IL-2 pre-treated CD19 cells (Biological)
IL-7/IL-15 pre-treated CD19 cells
Initial therapy: IL-7/IL-15 stimulated, CD28-ζ-vector transfected T cells(TCRζ chimeric antigen receptor-T cell)， were administered at 1×106/kg by single infusion
干预措施: IL-7/IL-15 pre-treated CD19 cells (Biological)
结局指标
主要结局
overall survival
时间窗: 5 year
次要结局
- progression-free survival(56 day)
- Objective Response Rate(56 day)
研究者
jiangjingting
Professor
The First People's Hospital of Changzhou