Cytotoxic T-Lymphocytes for EBV-positive Lymphoma, GRALE
关键词
抽象
描述
Subjects (or their syngeneic donor) will give blood for investigators to make EBV-specific (GRALE) T cells in the lab. These cells will be grown and frozen for the subject.
The GRALE T cells will then be thawed and injected into the subject over 1-10 minutes. Initially, two doses of GRALE T cells will be given 2 weeks apart.
If after the 2nd infusion there is a reduction in the size of the lymphoma on CT or MRI scan as assessed by a radiologist, the subject can receive additional doses of the GRALE T cells if they wish (up to 6 times). Follow up testing will be collected just like after the 1st infusion.
All of the treatments will be given by the Center for Cell and Gene Therapy at Texas Children's Hospital or Houston Methodist Hospital.
We will follow the subjects after the injections. They will either be seen in the clinic or the subject will be contacted by a research nurse yearly for 5 years.
If they receive additional doses of the GRALE T cells as described above, they will be followed until 5 years after the last dose of GRALE T-cells.
日期
| 最后验证: | 11/30/2019 |
| 首次提交: | 03/12/2012 |
| 提交的预估入学人数: | 03/14/2012 |
| 首次发布: | 03/15/2012 |
| 上次提交的更新: | 12/26/2019 |
| 最近更新发布: | 01/01/2020 |
| 实际学习开始日期: | 12/31/2012 |
| 预计主要完成日期: | 11/30/2020 |
| 预计完成日期: | 06/30/2022 |
状况或疾病
干预/治疗
Biological: EBV-specific T cells: A
Biological: EBV-specific T cells: B
相
手臂组
| 臂 | 干预/治疗 |
|---|---|
| Experimental: EBV-specific T cells: A Group A: Patients in second or subsequent relapse (or first relapse or with active disease if immunosuppressive chemotherapy contraindicated or multiple relapsed patients in remission who are at a high risk of relapse)** or any patient with primary disease or in first or subsequent remission if immunosuppressive chemotherapy is contraindicated.
Patients will be treated at Dose Level 3. Each patient will receive 2 injections, 14 days apart, according to the following dosing schedule:
Day 0: 1 x 10^8 cells/m2
Day 14: 2 x 10^8 cells/m2
** Patients with relapsed or refractory lymphoma that are eligible for a stem cell transplant will not be treated on this study as an alternative to transplant. | Biological: EBV-specific T cells: A Dose Level 3: 1 x 10^8 cells/m2 + 2 x 10^8 cells/m2 |
| Experimental: EBV-specific T cells: B Group B: Patients in remission or with minimal residual disease (MRD) status after autologous or syngeneic SCT.
Patients will be treated at Dose Level 3. Each patient will receive 2 injections, 14 days apart, according to the following dosing schedule:
Day 0: 1 x 10^8 cells/m2
Day 14: 2 x 10^8 cells/m2 | Biological: EBV-specific T cells: B Dose Level 3: 1 x 10^8 cells/m2 + 2 x 10^8 cells/m2 |
资格标准
| 有资格学习的性别 | All |
| 接受健康志愿者 | 是 |
| 标准 | Inclusion Criteria at time of Procurement 1. Any patient, regardless of age or sex, with EBV-positive Hodgkin's or non-Hodgkin's Lymphoma, (regardless of the histological subtype) or EBV (associated)-T/NK-lymphoproliferative disease or Severe Chronic Active EBV (CAEBV) who may subsequently be eligible for the treatment component 2. EBV positive tumor (can be pending at this time) 3. Weighs at least 12kg 4. Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent. Inclusion Criteria at time of Infusion 1. Any patient, regardless of age or sex, with EBV-positive Hodgkin's or non-Hodgkin's Lymphoma (regardless of histologic subtype), or EBV (associated)-T/NK-lymphoproliferative disease or Severe Chronic Active EBV (CAEBV)* and In second or subsequent relapse (or first relapse or with active disease if immunosuppressive chemotherapy contraindicated or multiply relapsed patients in remission who have a high risk of relapse)** OR any patient with primary disease or in first remission if immunosuppressive chemotherapy is contraindicated, e.g. patients who develop Hodgkin disease after solid organ transplantation or if the Lymphoma is a second malignancy e.g. a Richter's transformation of CLL. (Group A) OR In remission or with minimal residual disease status after autologous or syngeneic SCT. (Group B) 2. EBV positive tumor 3. Patients with life expectancy greater than or equal 6 weeks. 4. Patients with bilirubin less than or equal to 3x upper limit of normal, AST less than or equal 5x upper limit of normal, and hemoglobin greater than or equal to 7.0 (may be a transfused value). 5. Patients with a creatinine less than or equal to 2x upper limit of normal for age 6. Pulse oximetry of > 90% on room air 7. Patients should have been off other investigational therapy for 4 weeks prior to entry in this study. PD1/PDL inhibitors will be allowed if medically indicated. 8. Patients with a Karnofsky/Lansky score of greater than or equal to 50 9. Sexually active patients must be willing to utilize one of the more effective birth control methods during the study and for 6 months after the study is concluded. The male partner should use a condom. 10. Informed consent explained to, understood and signed by patient/guardian. Patient/guardian given copy of informed consent. - CAEBV is defined as patients with high EBV viral load in plasma or PBMC (> 4000 genomes per ug PBMC DNA) and/or biopsy tissue positive for EBV - Patients with relapsed or refractory lymphoma that are eligible for a stem cell transplant will not be treated on this study as an alternative to transplant. Exclusion Criteria at Time of Procurement 1. Active infection with HIV, HTLV, HBV, HCV (can be pending at this time) Exclusion Criteria at Time of Infusion 1. Pregnant or lactating 2. Severe intercurrent infection. 3. Current use of systemic corticosteroids > 0.5 mg/kg/day |
结果
主要结果指标
1. Assessment of toxicity of escalating doses of LMP, BARF1 and EBNA1 T lymphocytes [8 weeks]
次要成果指标
1. Determine survival and immune function of LMP/BARF1/EBNA1-specific cytotoxic T-lymphocyte lines [1 year]
2. Assess anti-viral and anti-tumor effects of LMP/BARF1/EBNA1-specific EBVST [1 year]
