Pilot Study of Autologous Anti-CD19 4-1BB CAR T Cells With Cell-intrinsic PD1 Inhibition in Relapsed or Refractory B-cell Lymphoma
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- safety of infusion of iPD1 CD19 eCAR T cells as assessed by the incidents of treatment related adverse events per NCI CTCAE V4.0
研究概览
简要总结
PD1 pathway is critical in determining the response to CAR T cell therapy. Emerging data suggested that Inhibition of PD1 could enhance the efficacy of CAR T cell therapy. iPD1 CD19 eCAR T cells is an enhanced version of the classical 2nd generation anti-CD19 4-1BB-costimulatory chimeric antigen receptor engineered T cells with cell-intrinsic PD1 inhibition by incorporation of a PD1 shRNA-expressing cassette in the CAR lentivector. This design will enhance the anti-tumor activities of CAR T cells by inhibiting PD1 induction after CAR T cell activation. This pilot, single arm, one center, dose-escalation, open label study is to determine the safety and efficacy of iPD1 CD19 eCAR T cells in relapsed or refractory CD19 positive lymphoma.
Subjects will be given a lymphodepletion chemotherapy comprised of Fludarabine and cyclophosphamide prior to CAR T cell infusion. The chemotherapy is completed 1 to 4 days before the first dost of iPD1 CD19 eCAR T cells.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •CD19+ B cell lymphoma,verified by IHC or flow cytometry.
- •a prior history of at least one standard care of medication.
- •ineligible for allogeneic transplantation or relapsed after transplantation.
- •patients are 18 years older.
- •life expectancy > 3months.
- •satisfactory major organ functions: adequate heart function with LVEF≥50%; pulse oximetry of ≥ 90%; cockcroft-gault creatinine clearance≥40 ml/min; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3ULN; Bilirubin ≤2.0 mg/dl .
- •Blood: Hgb ≥ 80 g/L, ANC ≥ 1×10^9/L, PLT ≥ 50×10^9/L.
- •women of reproductive potential must have a negative pregnancy test. Male and female of reproductive potential must agree to use birth control during the study and one year post study.
- •measurable tumors.
排除标准
- •using immunosuppressive drugs or systemic steroids within one week of enrollment.
- •active infection.
- •HIV positive.
- •active hepatitis B virus infection or hepatitis C virus infection.
- •breastfeeding or pregnant women.
- •patients refuse to practice birth control during study and one year post study.
- •patients with a prior history of other malignances will be excluded from this study, but patients who have been cured from skin basal cell carcinoma or cervical cancer, or who have had their tumors removed by surgical resection but without further therapies and have more than 5 years of progression-free survival, can be included into the study.
- •currently enrolled in other study.
- •patients, in the opinion of investigators, may not be eligible or are not able to comply with the study.
研究组 & 干预措施
iPD1 CD19 eCAR T cells
patients will receive a lymphodepletion chemotherapy prior to CAR T cell infusion
干预措施: iPD1 CD19 eCAR T cells (Biological)
iPD1 CD19 eCAR T cells
patients will receive a lymphodepletion chemotherapy prior to CAR T cell infusion
干预措施: Fludarabine and cyclophosphamide (Drug)
结局指标
主要结局
safety of infusion of iPD1 CD19 eCAR T cells as assessed by the incidents of treatment related adverse events per NCI CTCAE V4.0
时间窗: 2 years
incidents of treatment related adverse events per NCI CTCAE V4.0
次要结局
- treatment response(6 months)
- overall survival(3 years)
- progression-free survival(2 years)
研究者
Jun Zhu
Professor
Peking University