Phase 1 Dose Escalation Study of CD19/CD22 Chimeric Antigen Receptor (CAR) T Cells in Children and Young Adults With Recurrent or Refractory CD19/CD22-expressing B Cell Malignancies

National Cancer Institute (NCI)1 个研究点分布在 1 个国家目标入组 54 人开始时间: 2018年3月26日最近更新: 2025年6月4日

适应症

干预措施

试验速览

阶段: 1 期
状态: 已完成
发起方: National Cancer Institute (NCI)
入组人数: 54
试验地点: 1
主要终点: Grades of Toxicity by Type of Toxicity

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

Background:

B-cell leukemias and lymphomas are cancers that are often difficult to treat. The primary objective of this study is to determine the ability to take a patient's own cells (T lymphocytes) and grow them in the laboratory with the cluster of differentiation 19 (CD19/cluster of differentiation 22-chimeric antigen receptor (CD22-CAR) gene through a process called 'lentiviral transduction (also considered gene therapy) and growing them to large numbers to use as a treatment for hematologic cancers in children and young adults.. Researchers want to see if giving modified CD19/CD22-CAR T cells to people with these cancers can attack cancer cells. In addition, the safety of giving these gene modified cells to humans will be tested at different cell doses. Additional objectives are to determine if this therapy can cause regression of B cell cancers and to measure if the gene modified cells survive in patients' blood.

Objective:

To study the safety and effects of giving CD19/CD22-CAR T cells to children and young adults with B-cell cancer.

Eligibility:

People ages 3-39 with certain cancers that have not been cured by standard therapy. Their cancer tissue must express the CD19 protein.

Design:

A sample of participants blood or bone marrow will be sent to National Institutes of Health (NIH) and tested for leukemia.

Participants will be screened with:

Medical history

Physical exam

Urine and blood tests (including for human immunodeficiency virus (HIV)

Heart and eye tests

Neurologic assessment and symptom checklist.

Scans, bone marrow biopsy, and/or spinal tap

Some participants will have lung tests.

Participants will repeat these tests throughout the study and follow-up.

Participants will have leukapheresis. Blood will be drawn from a plastic tube (intravenous (IV) or needle in one arm then go through a machine that removes lymphocytes. The remaining blood will be returned to the participant's other arm.

Participants will stay in the hospital about 2 weeks. There they will get:

Two chemotherapy drugs by IV

Their changed cells by IV

Standard drugs for side effects

Participants will have frequent follow-up visits for 1 year, then 5 visits for the next 4 years. Then they will answer questions and have blood tests every year for 15 years.

...

详细描述

Background:

Acute lymphoblastic leukemia (ALL) accounts for approximately 25% of childhood cancer. Survival rates have improved, but outcomes for some subgroups, including infants and young adults remain poor, and survival for patients who relapse is < 50%, despite allogeneic stem cell transplant following second remission.
Cluster of differentiation 19 (CD19 immune escape has been observed by several groups following CD19-chimeric antigen receptor (CAR) therapy for B-ALL. Investigation of this phenomenon reveals a complex biology responsible for loss or downregulation of CD19 expression observed in these cases.
Sequential therapy using cluster of differentiation 22 (CD22)-CARs to treat CD19 dim/lo escape is associated with rapid development of resistance due to CD22 downregulation. This trial will test whether simultaneous targeting of CD19 and CD22 using a novel bivalent CD19/22-CAR is safe and feasible.

Objectives:

-Assess the safety of administering escalating doses of autologous CD19/CD22-CAR engineered T cells that meet established release specifications in children and young adults with CD19+CD22+ B cell ALL, isolated central nervous system (CNS) ALL, or lymphoma following a cyclophosphamide/fludarabine conditioning regimen.

Eligibility:

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: 3 Years 至 39 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