Administration of Rapidly Generated EBV-Specific Cytotoxic T-Lymphocytes To Patients With EBV-Positive Lymphoma
概览
- 阶段
- 1 期
- 干预措施
- EBV-specific T cells: A
- 疾病 / 适应症
- Hodgkin's Disease
- 发起方
- Baylor College of Medicine
- 入组人数
- 136
- 试验地点
- 5
- 主要终点
- Assessment of toxicity of escalating doses of LMP, BARF1 and EBNA1 T lymphocytes
- 状态
- 招募中
- 最后更新
- 2个月前
概览
简要总结
Subjects have a type of lymph gland disease called Hodgkin or non-Hodgkin Lymphoma or T/NK-lymphoproliferative disease or severe chronic active Epstein Barr Virus (CAEBV) which has come back, is at risk of coming back, or has not gone away after treatment, including the best treatment investigators know for these diseases.
Some of these patients show signs of virus that is called Epstein Barr virus (EBV) that causes mononucleosis or glandular fever ("mono" or the "kissing disease") before or at the time of their diagnosis. EBV is found in the cancer cells of up to half the patients with HD and NHL, suggesting that it may play a role in causing Lymphoma. The cancer cells and some immune system cells infected by EBV are able to hide from the body's immune system and escape destruction. Investigators want to see if special white blood cells, called GRALE T cells, that have been trained to kill EBV infected cells can survive in the blood and affect the tumor.
Investigators have used this sort of therapy to treat a different type of cancer called post transplant lymphoma. In this type of cancer the tumor cells have 9 proteins made by EBV on their surface. Investigators grew T cells in the lab that recognized all 9 proteins and were able to successfully prevent and treat post transplant lymphoma. However, in HD and NHL, T/NK-lymphoproliferative disease, and CAEBV, the tumor cells and B cells only express 4 EBV proteins. In a previous study, the investigators made T cells that recognized all 9 proteins and gave them to patients with HD. Some patients had a partial response to this therapy but no patients had a complete response. The investigators then did follow up studies where investigators made T cells that recognized the 2 EBV proteins seen in patients with lymphoma, T/NK-lymphoproliferative disease and CAEBV. Investigators have treated over 50 people on those studies. About 60% of those patients who had disease at the time they got the cells had responses including some patients with complete responses. This study will expand on those results and the investigators will try and make the T cells in the lab in a simpler faster way. These cells are called GRALE T cells. These GRALE T cells are an investigational product not approved by the FDA.
The purpose of this study is to find the largest safe dose of LMP-specific cytotoxic GRALE T cells created using this new manufacturing technique. Investigators will learn what the side effects are and to see whether this therapy might help patients with HD or NHL or EBV associated T/NK-lymphoproliferative disease or CAEBV.
详细描述
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. In this study, patients may also receive cyclophosphamide and fludarabine. These two drugs are standard chemotherapy medicines and may be given before the T cells to make space in the blood for the T cells to grow after receiving them. These drugs will be given intravenously daily over three days. 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 demonstrated partial response or stable disease 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. Investigators 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. For patients who receive more than one infusion, follow up will continue every 3 months until 12 months after the last infusion, then yearly thereafter for 5 years.
研究者
Helen Heslop
Professor
Baylor College of Medicine
入排标准
入选标准
- •at time of Procurement
- •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
- •EBV positive tumor (can be pending at this time)
- •Weighs at least 12kg
- •Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent.
- •Inclusion Criteria at time of Infusion
- •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)
- •In remission or with minimal residual disease status after autologous or syngeneic SCT. (Group B)
- •EBV positive tumor
排除标准
- •at Time of Procurement
- •1\. Active infection with HIV, HTLV, HBV, HCV (can be pending at this time)
- •Exclusion Criteria at Time of Infusion
- •Pregnant or lactating
- •Severe intercurrent infection.
- •Current use of systemic corticosteroids \> 0.5 mg/kg/day
研究组 & 干预措施
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 may receive cells with or without lymphodepletion. 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.
干预措施: EBV-specific T cells: A
EBV-specific T cells: B
Group B: Patients in remission or with minimal residual disease (MRD) status after autologous or syngeneic SCT. Patients may receive cells with or without lymphodepletion. 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
干预措施: EBV-specific T cells: B
结局指标
主要结局
Assessment of toxicity of escalating doses of LMP, BARF1 and EBNA1 T lymphocytes
时间窗: 8 weeks
To determine the safety of escalating doses of 2 intravenous injections of autologous or syngeneic rapid LMP, BARF1 and EBNA1 specific T-lymphocytes (VSTs) in patients with EBV-associated Hodgkin's Disease or non-Hodgkin's lymphoma or T/NK-lymphoproliferative disease and CAEBV.
次要结局
- Assess anti-viral and anti-tumor effects of LMP/BARF1/EBNA1-specific EBVST(1 year)
- Determine survival and immune function of LMP/BARF1/EBNA1-specific cytotoxic T-lymphocyte lines(1 year)