Infusion of Allogeneic, 3rd Party CD19-specific T Cells for Patients With Refractory CD19+ B-Lineage Lymphoid Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 主要终点
- Maximum Tolerated Dose (MTD) of CD19-Specific T Cells
研究概览
简要总结
The goal of this clinical research study is to learn if researchers can successfully and safely give patients who have had a stem cell transplant an infusion of white blood cells (called T-cells) that have been collected from an unrelated person, and that have been genetically changed. The process of changing the DNA (genetic material) of these T-cells is called "gene transfer." The gene transfer involves drawing blood from an unrelated donor, separating out T cells using a machine, changing the cells' DNA in the laboratory, and returning the genetically changed cells back to the body. T-cells are a type of white blood cell that fight infection. The type of gene transfer being used in this study is designed to help your T-cells to better fight cancer by targeting a chemical marker that is found on certain cancer cells.
Researchers want to learn if these genetically-changed T-cells can help to control B-cell leukemia or lymphoma after a stem cell transplant.
Researchers want to find out the highest tolerable dose of these T-cells that can be given to patients with relapsed leukemia or lymphoma.
详细描述
Study Plan:
This study has 2 steps: chemotherapy and gene transfer.
The chemotherapy combination in this study (fludarabine and cyclophosphamide) is given to try to help the T-cells work better.
Study Groups:
If the participant is found to be eligible to take part in this study, the participant will be assigned to a dose level of T-cells based on when the participant joined this study. The first group of 3 participants will receive the lowest dose of T-cells. Each new group will receive a higher dose of T-cells than the group before it, if no intolerable side effects were seen. Up to 6 dose levels of T-cells will be tested.
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
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with a history of refractory B-cell lymphoid malignancies: 1) acute lymphoblastic leukemia (ALL), CD19+, 2) biphenotypic leukemia CD19+, 3) non-Hodgkin's Lymphoma (NHL), which includes diffuse large B-cell lymphoma, small lymphocytic lymphoma, follicular lymphoma, mantle cell lymphoma, or chronic lymphocytic leukemia (CLL).
- •Age 18 to 70 years.
- •Zubrod performance 0-2 or Karnofsky greater than or equal to 60%.
- •Patient or patient's legal representative able to provide written informed consent.
- •Patient or patient's legal representative able to provide written informed consent for the long-term follow-up gene therapy study.
- •Patients must be a minimum of 3 months from last hematopoietic stem cell transplant (HSCT) and 3 weeks from last systemic chemotherapy.
排除标准
- •Patients with known allergy to bovine or murine products.
- •Clinically significant acute or chronic GVHD requiring systemic immunosuppression, including methylprednisolone >/= 1 mg/kg/day.
- •Systemic corticosteroid use within 72 hours of treatment initiation.
- •Antibody to HLA expressed on 3rd party T cells.
- •Experiencing any new Grade >2 (CTC version 4) adverse neurologic, pulmonary, cardiac, gastrointestinal, renal or hepatic (excluding albumin) event within 24 hours prior to treatment initiation.
- •Active infection defined as positive culture, if available, for bacteria, fungus, or virus within a 3-day period prior to treatment initiation and/or fever greater than 38°C within 24 hours prior to treatment initiation.
- •Positive beta HCG by qualitative pregnancy test in female of child-bearing potential defined as not post menopausal for 12 months or absence of previous surgical sterilization.
研究组 & 干预措施
T-Cell Administration
Cyclophosphamide 60 mg/kg by vein for 2 consecutive days, followed by Fludarabine at 25 mg/m2/day by vein for 5 consecutive days. Fludarabine dose calculated per adjusted ideal body weight.
T-cell product divided into 2 portions. Up to 25% of the genetically modified cells given on first day, with plan to infuse up to 75% of the remaining T-cell dose no sooner than 24 hours after completion of first portion. Second portion should not be given later than 72 hours after first portion. First group of 3 participants receive lowest dose of T-cells. Each new group receive a higher dose of T-cells than the group before it, if no intolerable side effects were seen. Up to 6 dose levels of T-cells will be tested.
干预措施: Cyclophosphamide (Drug)
T-Cell Administration
Cyclophosphamide 60 mg/kg by vein for 2 consecutive days, followed by Fludarabine at 25 mg/m2/day by vein for 5 consecutive days. Fludarabine dose calculated per adjusted ideal body weight.
T-cell product divided into 2 portions. Up to 25% of the genetically modified cells given on first day, with plan to infuse up to 75% of the remaining T-cell dose no sooner than 24 hours after completion of first portion. Second portion should not be given later than 72 hours after first portion. First group of 3 participants receive lowest dose of T-cells. Each new group receive a higher dose of T-cells than the group before it, if no intolerable side effects were seen. Up to 6 dose levels of T-cells will be tested.
干预措施: Fludarabine (Drug)
T-Cell Administration
Cyclophosphamide 60 mg/kg by vein for 2 consecutive days, followed by Fludarabine at 25 mg/m2/day by vein for 5 consecutive days. Fludarabine dose calculated per adjusted ideal body weight.
T-cell product divided into 2 portions. Up to 25% of the genetically modified cells given on first day, with plan to infuse up to 75% of the remaining T-cell dose no sooner than 24 hours after completion of first portion. Second portion should not be given later than 72 hours after first portion. First group of 3 participants receive lowest dose of T-cells. Each new group receive a higher dose of T-cells than the group before it, if no intolerable side effects were seen. Up to 6 dose levels of T-cells will be tested.
干预措施: T-Cell Infusion (Procedure)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of CD19-Specific T Cells
时间窗: 12 hours
Maximum tolerated dose (MTD) is highest dose level 6 patients treated, with at most 2 experiencing dose limiting toxicity (DLT). DLT defined as new adverse event attributable to CD19-specific T cells of grade \>3 that lasts for more than 3 days, and related to CD19-specific T cells within 30 days of an infusion. Grade 3/4 graft versus host disease (GVHD) occurring within 6 weeks of CD19-specific T cells administration, also a DLT. Graft failure following CD19-specific T cells administration considered DLT.
次要结局
未报告次要终点