Pediatric and Young Adult Leukemia Adoptive Therapy (PLAT)-03: A Pilot Feasibility and Safety Study of CD19t T-Antigen Presenting Cells (T-APCs) Following CAR T Cell Immunotherapy for CD19+ Leukemia
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- The adverse events associated with one or multiple CD19t T-APC product infusions will be assessed.
研究概览
简要总结
Patients with relapsed or refractory CD 19+ leukemia who have achieved remission after CD19 CAR-T cell treatment sometimes relapse because the CD 19 CAR-T cells decrease in number over time. Study PLAT-03 will test whether administering T cell antigen presenting cells (T-APCs) at intervals following treatment with CAR-T cells improves CD 19 CAR-T cell persistence and reduces the incidence of leukemia relapse.
详细描述
This pilot study seeks to examine the feasibility and safety of administering T cell antigen presenting cells (T-APCs) designed to reactivate and numerically expand CD19-specific CAR T cells. The underlying hypothesis to be examined is that after remission is achieved with CAR T cell treatment, the duration, magnitude, and activation state of persisting memory CAR T cells impact on the potential for durable leukemia eradication. This is of particular relevance in two groups of patients we have identified: those who are predicted to lose persistence of their CAR T cells before Day 63, and those who have definitively lost persistence of CAR T cells prior to 6 months. By providing these patients with episodic exposure to T-APCs capable of activating CD19-specific CAR T cells for proliferation and redistribution to tissue beds where tumor cells of ALL seed, ideally over several months following remission induction, it is posited that the incidence of disease relapse will be diminished.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Year 至 30 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of recurrent or refractory CD19+ leukemia
- •Adequate performance status
- •Able to tolerate apheresis, including placement of temporary apheresis line if required
- •Adequate renal, liver, cardiac, and respiratory function
- •Adequate absolute lymphocyte count
- •HIV negative; Hepatitis B and C negative within 3 months prior to enrollment.
排除标准
- •Evidence of active clinically significant CNS dysfunction
- •Evidence of active malignancy other than CD19+ malignancy
- •Evidence of active GVHD, or on immunosuppressive GVHD therapy within 4 weeks prior to enrollment
研究组 & 干预措施
Cohort C
Participants will receive CD19-targeting CAR T cells. Participants for whom laboratory testing shows loss of CAR T cells within 6 months will be assigned to Cohort C. They will receive another CAR T cell infusion followed by up to 6 T-APC treatments.
干预措施: T-cell Antigen Presenting Cells expressing truncated CD19 (T-APC) (Biological)
Cohort A
Participants will receive CD19-targeting CAR T cells. Participants who have a total CD19 antigen load in bone marrow of <15% will be assigned to Cohort A, to receive up to 6 T-APC treatments.
干预措施: T-cell Antigen Presenting Cells expressing truncated CD19 (T-APC) (Biological)
Cohort D
Participants will receive CD19-targeting CAR T cells. Participants who do not meet assignment rules for Cohorts A, B, or C will be followed after CAR T cell infusion in Cohort D.
干预措施: T-cell Antigen Presenting Cells expressing truncated CD19 (T-APC) (Biological)
Cohort B
Participants will receive CD19-targeting CAR T cells. Participants for whom laboratory testing on Study Day 14 indicates they are at risk for early loss of CAR T cells will be assigned to Cohort B to receive up to 6 T-APC treatments. If laboratory testing prior to planned T-APC treatment indicates loss of CAR-T cells, participants may move to Cohort C.
干预措施: T-cell Antigen Presenting Cells expressing truncated CD19 (T-APC) (Biological)
结局指标
主要结局
The adverse events associated with one or multiple CD19t T-APC product infusions will be assessed.
时间窗: up to 6 months
Type, frequency, severity, and duration of adverse events will be summarized
Determine the feasibility of deriving and administering a CD19t T-APC product
时间窗: 28 days
Proportion of products successfully manufactured and infused
次要结局
- Quantification of changes in the number of CAR T cells in peripheral blood before and after receiving CD19t T-APCs(6 months)
- Duration of B cell aplasia in CD19t T-APC treated patients(up to 5 years)
研究者
Colleen Annesley
Medical Director, Seattle Children's Therapeutics
Seattle Children's Hospital