Phase I Study of T Cells Expressing an Anti-CD19 Chimeric Receptor in Children and Young Adults With B Cell Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 53
- 试验地点
- 2
- 主要终点
- Number of Participants in Which the Prescribed Dose of Cluster of Differentiation (CD)19-Chimeric Antigen Receptor (CAR): CD19 CAR T-cells Were Successfully Manufactured
研究概览
简要总结
Background:
- Although progress has been made in treating children with B-cell cancers such as leukemia or lymphoma, many children do not respond to the standard treatments. One possible treatment involves collecting white blood cells called T cells from the person with cancer and modifying the cells to attack the B-cell cancer. The cells can then be given back to the participant. This study will use T cells that have been modified to attack the cluster of differentiation 19 (CD19) protein, which is found on the surface of some B-cell cancers.
Objectives:
- To see if anti-CD19 modified white blood cells are a safe and effective treatment for children and young adults with advanced B-cell cancer.
Eligibility:
- Children and young adults between 1 and 30 years of age who have B-cell cancer (leukemia or lymphoma) that has not responded to standard treatments.
- The leukemia or the lymphoma must have the CD19 protein.
- There must be adequate organ function.
Design:
- Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. Imaging studies or bone marrow biopsies may be performed depending on the type of cancer.
- Participants will undergo a process where white blood cells are collected, called apheresis. These cells will be modified to contain the anti-CD19 gene.
- Participants will have 3 days of chemotherapy to prepare their immune system to accept the modified cells.
- Participants will receive an infusion of their own modified white blood cells. They will remain in the hospital until they have recovered from the treatment.
- Participants will have frequent follow-up visits to monitor the outcome of the treatment.
- If the participant benefits from the treatment, then he/she may have the option for another round of treatment.
详细描述
Background:
Chimeric antigen receptors (CAR) that recognize the cluster of differentiation 19(CD19) antigen have been constructed and are in clinical trials at several institutions. In this trial, the Pediatric Oncology Branch (POB) will utilize a chimeric receptor containing the signaling domains of cluster of differentiation 28 (CD28) and cluster of differentiation 3 (CD3)-zeta, currently under study in the Center for Cancer Research (CCR) in adults, for children and young adults with CD19 expressing malignancies.
In co-cultures with CD19-expressing acute lymphoblastic leukemia cells, anti-CD19-CAR-transduced T cells show robust killing, and in xenograft models, can rapidly clear CD19- expressing ALL cell lines.
Objectives:
- Primary: To determine the safety and feasibility of administering escalating doses of anti-CD19-CAR engineered peripheral blood lymphocytes in two strata (prior allogeneic stem cell transplant [SCT] vs. no prior SCT) of children and young adults with B cell malignancies following a cyclophosphamide/fludarabine preparative regimen. COMPLETED March 2014.
- Primary: To determine the safety of administering cells in two groups of children and young adults with B-cell malignancies expressing CD19:
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
- 1 Year 至 30 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
结局指标
主要结局
Number of Participants in Which the Prescribed Dose of Cluster of Differentiation (CD)19-Chimeric Antigen Receptor (CAR): CD19 CAR T-cells Were Successfully Manufactured
时间窗: Apheresis through completion of CAR manufacturing process, approximately 2 weeks
Participants who had T-cells collected by apheresis and subsequently had the amount of CAR T-cells manufactured as prescribed by the dose level they were enrolled in.
Number of Participants Who Received Preparative Chemotherapy Followed by Cluster of Differentiation (CD)19-Chimeric Antigen Receptor (CAR): CD19 CAR T-cells With < Grade 4 Cytokine Release Syndrome
时间窗: Beginning of preparative regimen through Day 28 after CD19 CAR infusion
Participants with B cell malignancies who received preparative chemotherapy followed by CD19 CAR T-cells with \< Grade 4 cytokine release syndrome.
次要结局
- Number of Patients With a Complete Response (CR)(Day 28 (+/- 4 days) after CD19 CAR infusion)
- Number of Participants With Serious and Non-Serious Adverse Events(Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.)
- Number of Participants Who Were Administered Intensive Chemotherapy Prior to Cluster of Differentiation (CD)19-Chimeric Antigen Receptor (CAR): CD19 CAR Infusion(21 days of target date)
- Mean Percentage Cluster of Differentiation 19 (CD19) - Chimeric Antigen-Receptor (CAR) T-Cells in Blood, Bone Marrow (BM) and Cerebrospinal Fluid (CSF)(28 days (+/- 4 days) after infusion of CD19 CAR T-cells)
- Number of Participants With Grade 4 Cytokine Release Syndrome (CRS)(Day 28 (+/- 4 days) after CD19 CAR infusion.)
研究者
Nirali N. Shah, M.D.
Principal Investigator
National Cancer Institute (NCI)