Safety and Feasibility Study of CD19 Chimeric Antigen Receptor (CAR) T Cells in Children with Relapsed or Refractory CD19 Positive Acute Lymphoblastic Leukemia or Lymphoma
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Complete response rate (CRR) for ALL and Overall response rate (ORR) for lymphoma
研究概览
简要总结
This study seeks to examine the efficacy and safety of the administration of autologous T cells that have been modified through the introduction of a chimeric antigen receptor (CAR) targeting the B cell surface antigen CD19 following administration of chemotherapy lymphodepletion regimen in children with relapsed or refractory acute lymphoblastic leukemia (ALL) or lymphoma. The overall goal of this study is to validate the safety profile of administration CD19-CAR T cells and describe the response rate in children with relapsed/refractory ALL or lymphoma.
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 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects must have relapsed or refractory ALL or lymphoma treated with at least two lines of therapy. Disease must have either progressed after the last regimen or presented failure to achieve partial or complete remission with the last regimen.
- •The patient's disease must be CD19 positive, either by immunohistochemistry or flow cytometry analysis on the last biopsy available.
- •Age 1-17 years.
- •Performance status: Subjects > 10 years of age: Karnofsky ≥ 50%; Subjects ≤ 10 years of age: Lansky scale ≥ 50%.
- •Normal organ function.
- •Total bilirubin ≤ 3 times upper limit of normal
- •AST (SGOT) ≤ 5 times upper limit of normal
- •ALT (SGPT) ≤ 5 times upper limit of normal
- •Serum Creatinine ≤ 2 times upper limit of normal
- •Subjects must have the following hematologic function parameters: Hemoglobin (Hb) level > 8 g/dL; Absolute Lymphocyte Count > 0.1x10^9/L; Platelet > 50x10^9/L
- •Prior therapy wash-out. At least 2 weeks or 5 half lives, whichever is shorter, must have elapsed since any prior systemic therapy at the time the subject is planned for leukapheresis.
- •Subjects' parent or legal guardian must have the ability to understand and the willingness to sign a written informed consent document.
排除标准
- •Autologous transplant within 6 weeks of planned CAR T cell infusion.
- •Recipient of CAR-T cell therapy outside of this protocol.
- •Active central nervous system (CNS) or meningeal involvement by tumor.
- •History of additional active malignancy other than non-melanoma skin cancer, carcinoma in situ (e.g. cervix, bladder, breast).
- •Active human immunodeficiency virus (HIV) infection.
- •Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, pulmonary abnormalities or psychiatric illness/social situations that would limit compliance with study requirements.
- •Pregnant or breastfeeding women.
- •Evidence of myelodysplasia or cytogenetic abnormality indicative of myelodysplasia on any bone marrow biopsy prior to initiation of therapy.
- •Serologic status reflecting active hepatitis B or C infection.
研究组 & 干预措施
CAR-T cell therapy
CAR-T cell infusion intravenously once
干预措施: CAR-T (Biological)
结局指标
主要结局
Complete response rate (CRR) for ALL and Overall response rate (ORR) for lymphoma
时间窗: 1 month for subjects with ALL, and 3 months for subjects with lymphoma
Complete response for ALL was defined as leukemic cells \<5% in bone marrow. Overall response for lymphoma was defined as complete response plus partial response defined by Lugano criteria.
Incidence and severity of adverse events
时间窗: through study completion, an average of 6 months
Severity of adverse events are graded according to CTCAEv5.0.
次要结局
- Frequency of minimal residual disease for ALL(1 month)
- Overall survival(1 year)
- Event-free survival(1 year)
- Proportion of products successfully manufactured(at the time of CAR-T cell infusion)
研究者
Cheuk Ka Leung Daniel
Consultant
Hong Kong Children's Hospital