A Phase I Trial Evaluating the Safety of Consolidative Infusions of CD19-Specific Chimeric Antigen Receptor (CAR) T Cells Following T-cell Depleted Allogeneic Transplantation for High Risk B-cell Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Maximum tolerated dose (MTD)
研究概览
简要总结
The purposed of this study is to determine whether an infusion with specialized 'modified T cells' (or CD19 chimeric antigen T cells, also called CD19 CAR T cells) that target the B cell marker will reduce the risk of relapse after transplant.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The following criteria must be met prior to the allogenic transplantation:
- •ALL in second remission or greater (≥ CR2)
- •Please refer to section 3.0 for more discussion of ALL in CR1 versus CR2
- •High risk in any remission status as defined by 17p deletion or Richter's transformation, or
- •All other patients eligible after at least 2 lines of standard or investigational chemotherapy
- •Refractory or stable disease to last line of therapy per ICML
- •Patients should have at least 2 lines of prior therapy.
- •Relapsed disease in patients who are not candidates for autologous transplant
- •Patient's age is ≥ 18 and ≤
- •Patients must have CD19 expression (by any detection method) demonstrated on their malignant cells at the time of enrollment on the protocol.
- •Patients relapsed after prior CD19 CAR T cell or blinatumomab are eligible for enrollment as long as CD19 expression is still prese on the malignant cells.
- •Patients who have a matched related donor willing to donate HSC for allograft and PBMC for CAR T cell generation
- •Patients must have adequate organ function measured by:
- •Cardiac: asymptomatic or if symptomatic then LVEF at rest must be > 50%
- •Hepatic: < 3x ULN ALT and < 1.5 total serum bilirubin, unless there is congenital benign hyperbilirubinemia.
- •Renal: serum creatinine <1.3 mg/dl or if serum creatinine is outside the normal range, then CrCl > 60 ml/min (measured or calculated/estimated)
- •Pulmonary: asymptomatic or if symptomatic, DLCO > 50% of predicted (corrected for hemoglobin)
- •Negative serum pregnancy test for women of child-bearing potential is required
排除标准
- •Active and uncontrolled infection at time of transplantation. Please note that patients being actively treated for a viral reactivation may be enrolled on the protocol at the discretion of the investigators.
- •Patients who have undergone a prior allogeneic or autologous stem cell transplant within the previous six months.
- •Pregnant or breast feeding
- •HIV infection
- •Progressive disease at time of transplant
- •Patients with known autoimmune disease.
- •Patients with active or clinically significant neurological disorders, such as seizure disorders.
研究组 & 干预措施
Cohort -1
Cohorts of 3-6 patients each will be treated with escalating doses of consolidative modified T cells at Day 30 (+/- 5 days) post allo-HSCT
Total T-Cell Dose: 1 x 10^4 cells/kg
干预措施: CAR T-Cell Infusion (Biological)
Cohort 1
Cohorts of 3-6 patients each will be treated with escalating doses of consolidative modified T cells at Day 30 (+/- 5 days) post allo-HSCT
Total T-Cell Dose: 1 x 10^5 cells/kg
干预措施: CAR T-Cell Infusion (Biological)
Cohort II
Cohorts of 3-6 patients each will be treated with escalating doses of consolidative modified T cells at Day 30 (+/- 5 days) post allo-HSCT
Total T-Cell Dose: 2 x 10^5 cells/kg
干预措施: CAR T-Cell Infusion (Biological)
Cohort III
Cohorts of 3-6 patients each will be treated with escalating doses of consolidative modified T cells at Day 30 (+/- 5 days) post allo-HSCT
Total T-Cell Dose: 4 x 10^5 cells/kg
干预措施: CAR T-Cell Infusion (Biological)
结局指标
主要结局
Maximum tolerated dose (MTD)
时间窗: 24 month
To determine maximum tolerated dose (MTD) of intravenously administered allogeneic, donor-derived 19-28z CAR T cells administered following TCD allo-HSCT for patients with high-risk CD19+ malignancies
次要结局
未报告次要终点