A Phase 1 / 2 Single Arm Study of T-cells Expressing Anti-CD19 Chimeric Antigen Receptor in Pediatric and Young Adult Patients With B-cell Malignancies
试验速览
- 阶段
- 1 期
- 入组人数
- 300
- 试验地点
- 1
- 主要终点
- Overall Response Rate
研究概览
简要总结
This phase 1 / 2 study will evaluate the response of B-cell malignancies expressing CD19 to autologous T cells transduced with a second generation anti-CD19 chimeric antigen receptor in children and young adults.
详细描述
Autologous T cells transduced with chimeric antigen receptors (CAR) that recognize the CD19 antigen (CD19-CAR T cells) have been used in multiple clinical trials at several institutions worldwide. We established an in-house manufacturing process for CD19-CAR T cells with a CD28 (cluster of differentiation 28) costimulatory domain.
Primary Objectives:
- To study the safety of administration of CAR T cell at the Sheba Medical Center
- To determine the feasibility and efficacy of administering anti-CD19-CAR T cells in children and young adults with B cell malignancies.
Secondary Objectives
- To study in vivo and in vitro behavior of CAR T cell in patients, including persistence, expansion, cytotoxic potential and exhaustion.
- To study the cytokine milieu in CAR treated patients.
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
- 1 Year 至 50 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient with relapsed or refractory B-cell malignancy
- •Age 1-50 years
- •CD19 expression shown by flow cytometry or immunohistochemistry on at least 70% of leukemic blasts / lymphoma cells
- •Adequate CD3 count (above 250 CD3+ cells per microliter blood)
- •Clinical performance status: Patients > 10 years of age: Karnofsky ≥ 50%; Patients ≤ 10 years of age: Lansky scale ≥ 50%. Exception for neurologic symptoms (e.g. paralysis) that are explained by the malignancy.
- •Females of child-bearing potential must have a negative pregnancy test
- •Cardiac function: Left ventricular ejection fraction >45% or shortening fraction >28%
- •For patients following allogeneic bone marrow transplantation - at least 100 days post BMT with no signs or symptoms of active graft-versus-host disease.
排除标准
- •Hyperleukocytosis (WBC>50,000) or rapidly progressive disease
- •Pregnant or breast-feeding females
- •Hepatic dysfunction, defined as bilirubin > x2 upper normal limit (except when explained by hemolysis or Gilbert) or serum glutamate oxaloacetate transaminase > x25 upper normal limit.
- •Hepatitis B, Hepatitis C or HIV infection.
- •Anti-neoplastic treatment given in the 2 weeks prior to apheresis, with the exception of intrathecal chemotherapy.
- •Active immunosuppressive therapy
结局指标
主要结局
Overall Response Rate
时间窗: 28 days
Overall response rate = complete response (CR) + partial response (PR) + complete response with incomplete count recovery (CRi) in leukemia patients; Assessment using bone marrow evaluation for patients with leukemia, and imaging (CT / PET CT) for patients with lymphoma
Number of patients with treatment related adverse events as assessed by CTCAE v4.
时间窗: 2 years
Feasibility of CD19 CAR T cell production as defined by number of products successfully meeting release criteria
时间窗: 12 days
For each participant, the feasibility of generating sufficient autologous CAR T cells within 12 days will be evaluated.
次要结局
- Cytokine levels in the peripheral blood of the patients(30 days)
- CAR T cell persistence as measured by enumeration of CAR T cells in the blood and bone marrow of participants(1 year)
- T cell activity and exhaustion profile as measured by flow cytometry(3 months)