Viral Specific T-Lymphocytes by Cytokine Capture System (CCS) to Treat Infection With Adenovirus, Cytomegalovirus or Epstein-Barr Virus After Hematopoietic Cell Transplantation or Solid Organ Transplantation and in Patients With Compromised Immunity
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 25
- 试验地点
- 2
- 主要终点
- Grade III-IV Acute Graft versus host disease
研究概览
简要总结
The primary purpose of this phase I/II study is to evaluate whether partially matched, ≥2/6 HLA-matched, viral specific T cells have efficacy against adenovirus, CMV, and EBV, in subjects who have previously received any type of allogeneic HCT or solid organ transplant (SOT), or have compromised immunity. Reconstitution of anti-viral immunity by donor-derived cytotoxic T lymphocytes has shown promise in preventing and treating infections with adenovirus, CMV, and EBV. However, the weeks taken to prepare patient-specific products, and cost associated with products that may not be used limits their value. In this trial, we will evaluate viral specific T cells generated by gamma capture technology. Eligible patients will include HCT and/or SOT recipients, and/or patients with compromised immunity who have adenovirus, CMV, or EBV infection or refractory viremia that is persistent despite standard therapy. Infusion of the cellular product will be assessed for safety and efficacy.
详细描述
If a subject shows a partial response, defined as a decrease in viral load of at least 50% from baseline or 50% improvement of clinical signs and symptoms, or no response, they are eligible to receive up to 4 additional cellular infusions from the same donor, at a minimum of 14-day intervals. If the same donor is no longer available, eligible, or appropriate, another donor may be considered for a maximum of 4 total cellular infusions at the discretion of the study PI and treating physician. A subject will not exceed a maximum of 5 total infusions from 2 donors.
Subjects are followed for 6 months post initial viral-specific T cell infusion. If subjects receive additional infusion(s), GvHD and adverse events will be followed for an additional 90 days from last infusion. Data may be abstracted from subjects' medical charts for an additional 1 year after most recent viral-specific T cell infusion.
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
- 1 Month 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Received ATG or Alemtuzumab within 21 days of viral-specific T cell infusion and a lack of evidence of T cell survival, defined by <10 CD3+ T cells/uL (in unique situations, plasmapheresis may be considered).
- •Active acute GVHD grades II-IV.
- •Active severe chronic GVHD.
- •Received donor lymphocyte infusion, with the exception of a fraction of an umbilical cord blood, within 21 days of planned viral-specific T cell infusion. Subjects receiving a fraction of an umbilical cord blood within 21 days of the viral-specific T cell infusion will not be excluded.
- •Active and uncontrolled relapse of malignancy (other than EBV+ post-transplant lymphoproliferative disorder or lymphoma).
- •Anticipated initiation of new lymphotoxic therapy within 4 weeks of viral-specific T cell infusion.
- •Patients who are pregnant or lactating.
- •Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, or concomitant medications, which, in the opinion of the investigator, may pose additional risks to participation in the study, may interfere with the participant's ability to comply with study requirements, or that may impact the quality or interpretation of the data obtained from the study.
- •Donor Inclusion Criteria
- •Able to understand and sign the consent/assent to the procedure
- •Partial (2/6 or more) HLA match to the recipient
- •A pediatric donor could be selected as a donor only if a suitable adult donor is not available (as attested by the research team) or is ineligible according to FACT requirements. For pediatric donors:
- •Related to the recipient
- •Apheresis does not need a blood prime before the procedure
- •Adequate peripheral venous access
- •Explicit evaluation of the donors' willingness to donate cells, as attested by the research team
- •Must have understanding that they are helping their ill relative, as attested by the research team
- •Will gain emotional/psychological benefit from their ability to help and want to donate for a relative, as attested by the research team
- •Inclusion of minor donors that are not relatives of the recipient will need to be evaluated on a case-by-case basis for the IRB to evaluate the potential benefit to these participants (whether they will receive an emotional and psychological boost from helping the recipient) *If the only suitable donor is less than 12 years old, a single patient exception to this inclusion criteria will be submitted and approved by the IRB before obtaining the donor's assent and their LAR consent.
- •Donor Exclusion Criteria
- •Donor is pregnant
- •Donor is HIV positive
- •Donor is positive for hepatitis B and/or hepatitis C
- •Deemed to be a high-risk donor based on responses to donor risk questionnaire
- •Deemed high risk due to preexisting medical condition or abnormal lab results
研究组 & 干预措施
Viral Specific T-Lymphocytes
Peripheral blood mononuclear cells will be collected from the donor and loaded onto our Miltenyi Biotec CliniMACS® Plus where they will be stimulated in vitro with viral-specific antigen(s). The cells are then immunomagnetically labeled with interferon gamma via the cytokine capture system. By this method, viral specific, gamma-secreting T cells, are captured in a closed, sterile system.
干预措施: Adenovirus Specific T- Lymphocytes (Biological)
Viral Specific T-Lymphocytes
Peripheral blood mononuclear cells will be collected from the donor and loaded onto our Miltenyi Biotec CliniMACS® Plus where they will be stimulated in vitro with viral-specific antigen(s). The cells are then immunomagnetically labeled with interferon gamma via the cytokine capture system. By this method, viral specific, gamma-secreting T cells, are captured in a closed, sterile system.
干预措施: Cytomegalovirus Specific T-Lymphocytes (Biological)
Viral Specific T-Lymphocytes
Peripheral blood mononuclear cells will be collected from the donor and loaded onto our Miltenyi Biotec CliniMACS® Plus where they will be stimulated in vitro with viral-specific antigen(s). The cells are then immunomagnetically labeled with interferon gamma via the cytokine capture system. By this method, viral specific, gamma-secreting T cells, are captured in a closed, sterile system.
干预措施: Epstein-Barr Virus Specific T-Lymphocytes (Biological)
结局指标
主要结局
Grade III-IV Acute Graft versus host disease
时间窗: Day 0 through 90 days after last cellular infusion
The number of patients who develop Grade III-IV acute graft versus host disease (GVHD) attributed to the viral specific T cells.
CTCAE Grade 4/5 Adverse Events
时间窗: Day 0 through 30 days from last cellular infusion
The incidence of patients who develop CTCAE Grade 4/5 Adverse events related to infusion
次要结局
- Number of patients achieving 6-month survival (dichotomous)(First cellular infusion to 6 months post first cellular infusion)
- Viral load from Respiratory Viral Panel (RVP)(Baseline and 14 days, 1 month, 3 months, and 6 months after cellular infusion)
- Viral load from Stool(Baseline and 14 days, 1 month, 3 months, and 6 months after cellular infusion)
- Number of patient who require antiviral agents(Baseline and 14 days, 1 month, 3 months, and 6 months after cellular infusion)
- Viral load by Polymerase Chain Reaction (PCR)(Baseline and 14 days, 1 month, 3 months, and 6 months after cellular infusion)
- Viral load from Bronchoalveolar lavage (BAL)(Baseline and 14 days, 1 month, 3 months, and 6 months after cellular infusion)
- Viral load from fluid/tissue(Baseline and 14 days, 1 month, 3 months, and 6 months after cellular infusion)
- Viral load from Urine(Baseline and 14 days, 1 month, 3 months, and 6 months after cellular infusion)
- Clinical response to viral specific infusion(Baseline and 14 days, 1 month, 3 months, and 6 months after cellular infusion)
研究者
Jessie L. Alexander
Clinical Associate Professor of Pediatrics
Stanford University