CD19-Specific T Cell Infusion in Patients With B-Lineage Lymphoid Malignancies After Allogeneic Hematopoietic Stem Cell Transplantation
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 95
- 试验地点
- 2
- 主要终点
- Maximum Tolerated dose (MTD) of Donor Lymphocyte Infusion (DLI)
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 HSCT patients an infusion of white blood cells (called T-cells) that have been genetically changed. The process of changing the DNA (the genetic material in cells) of these T-cells is called "gene transfer." Researchers want to learn if these genetically-changed T-cells are effective in attacking cancer cells in patients with advanced B-cell lymphoma or leukemia, after they have received standard allogeneic HSCT. Researchers want to find out the highest dose of these special T-cells that can be given safely to leukemia and lymphoma patients. Researchers also want to learn how long the changed T-cells stay in your body, and if adding them to standard transplant can improve how you respond to treatment.
详细描述
Gene Transfer:
Gene transfer involves drawing blood from a transplant donor, and then separating out the T-cells using a machine. Researchers then perform a gene transfer to change the T-cells' DNA, and then inject the changed T-cells into the body of the patient receiving the transplant. This process is called a modified donor lymphocyte infusion (DLI).
Study Groups:
If you are found to be eligible to take part in this study, you will be assigned to 1 of 4 study arms, based on your age, treatment schedule, and disease status:
- Participants in Arm 1 will receive the T-cells by vein about 6-12 weeks after the stem cell transplant. (Adults participants only)
- Participants in Arm 2 will receive the T-cells by vein if, at any point, the disease comes back after stem cell transplant. Your doctor may decide that you need to receive chemotherapy before you are given the T-cells, in order to clear out the T-cells that are in your body already. This may help the infused T-cells work better. If more chemotherapy is needed, you will sign another informed consent document, which will the chemotherapy and its risks in detail. (Pediatric and adult participants eligible)
- Participants in Arm 3 will receive the T-cells by vein about 6-12 weeks after the stem cell transplant. (Pediatric participants [ages 1-17] only)
- Participants in Arm 4 will be given the T-cells as a scheduled infusion or if the disease comes back. This group is also scheduled to receive a stem cell transplant from a mismatched family member donor. (Pediatric and adult participants eligible)
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with a history of CD19+ lymphoid malignancies that are primary refractory to treatment (do not achieve complete remission after first course of therapy) or are beyond first remission including second or greater remission or active disease. Patients in first remission are eligible if they are considered high risk, defined as any of the following detected at any time:1) Acute Lymphoblastic Leukemia (ALL) with translocations 9;22 or 4;11, hypodiploidy, complex karyotype, secondary leukemia developing after cytotoxic drug exposure,and/or evidence of minimal residual disease, 2) acute biphenotypic leukemia, or 3) double hit nonHodgkin's lymphoma. Non-Hodgkin's Lymphoma (NHL) in second or third complete remission, or relapse (including relapse post autologous hematopoietic stem cell transplant). Double hit lymphomas in first remission or more advanced disease. Small Lymphocytic Lymphoma (SLL), or Chronic Lymphocytic Leukemia (CLL) with progressive disease following standard therapy.
- •Age 1 to 65 years old.
- •Lansky performance score >/= 60% for patients </= 16 years of age, or Zubrod performance 0-1 or Karnofsky greater than or equal to 80% for patients > 16 years of age.
- •Patient or patient's legal representative, parent(s) or guardian able to provide written informed consent.
- •Patient or patient's legal representative, parent(s) or guardian able to provide written informed consent for the long-term follow-up gene therapy study.
- •Patient is planning to receive or has received an HLA-identical matched family, related haploidentical donor (</= 7/8 allele match), or at least 8/8 matched unrelated allogeneic HSCT.
排除标准
- •Patients with known allergy to bovine or murine products.
- •Active grade 2-4 acute GVHD at time of DLI.
- •Systemic corticosteroid use within 72 hours of DLI unless required for physiologic replacement.
- •Less than 80% donor chimerism from peripheral blood within 30 days of DLI administration, if T cells are made from allogeneic donor.
- •Experiencing any new Grade >2 (CTC version 4) adverse neurologic, pulmonary, cardiac, gastrointestinal, renal or hepatic (excluding albumin) event within 24 hours prior to DLI.
- •Currently using an investigational agent at time of DLI.
- •Active infection defined as positive culture, if available, for bacteria, fungus, or virus within a 3-day period prior to DLI and/or fever greater than 38°C within 24 hours prior to DLI.
- •Positive beta HCG in female of child-bearing potential defined as not post menopausal for 12 months or absence of previous surgical sterilization.
- •Active CNS disease in patient with history of CNS malignancy.
- •Positive serology for HIV.
结局指标
主要结局
Maximum Tolerated dose (MTD) of Donor Lymphocyte Infusion (DLI)
时间窗: 3 months
MTD is highest dose level where 2 of 6 treated participants have dose limiting toxicity (DLT). DLT defined as new adverse event attributable to donor lymphocyte infusion (DLI) grade 3 or \> involving cardiopulmonary, gastrointestinal, hepatic (excluding albumin), neurological, or renal common toxicity criteria (CTC) version 4 parameters, lasts \> 3 days and possibly related to DLI within 30 days of infusion.
次要结局
未报告次要终点