Administration of Rapidly Generated Multipathogen-specific T-Lymphocytes for the Treatment of AdV, CMV, EBV, BKV and Aspergillus Fumigatus Infections Post Allogeneic Stem Cell Transplant
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- Acute GvHD
研究概览
简要总结
The purpose of the study is to determine the feasibility, safety and efficacy of administering rapidly-generated donor-derived pentavalent-specific T cells (Penta-STs) to mediate antiviral and antifungal activity in hematopoietic stem cell transplant (HSCT) recipients with AdV, EBV, CMV, BKV or Aspergillus fumigatus (AF) infection/ reactivation or with active disease.
详细描述
Reconstitution of anti-viral and antifungal immunity by donor-derived antigen-specific T cells has shown promise in preventing and treating infections with CMV, or/and EBV, or/and AdV or/and BKV, HHV6 or/and AF post-transplant. However, the broader implementation of T cell immunotherapy using conventional protocols is limited and until today it was practically impossible for Greece by the cost, the complexity and the time required for virus-specific T cells (VSTs) production and by the antigenic competition between different antigens, which limits the spectrum of viruses that can be targeted in a single T cell product.
In this trial, the investigators will evaluate the feasibility, safety and efficacy of donor-derived Penta-STs infusion to allogeneic HSCT recipients with confirmed AdV, EBV, CMV, BKV and AF infection.
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 64 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Received prior myeoloablative or nonmyeloablative allogeneic hematopoietic stem cell transplant.
- •Cells administered as treatment for single or multiple infections/reactivations of one or more of the following pathogens: AdV, CMV, EBV, ΒΚV and AF.
- •Karnofsky/Lansky score of ≥
- •ANC > 500/μl.
- •Bilirubin ≤ 2x*, AST < 3x*, Serum creatinine ≤ 2x*, Hemoglobin > 8.0 g/dl.
- •Pulse oximetry of > 90% on room air.
- •Available pentavalent-specific T cells.
- •Negative pregnancy test (if female of childbearing potential)
- •Patient capable of providing informed consent.
排除标准
- •Received ATG, or Campath or other T cell immunosuppressive monoclonal antibodies in the last 28 days.
- •Steroids > 0.5 mg/kg/day prednisone.
- •Received donor lymphocyte infusion in last 28 days.
- •GVHD ≥ grade
- •Active and uncontrolled relapse of malignancy.
- •Patients with other uncontrolled infections
研究组 & 干预措施
Penta-STs
Patients will receive penta-STs in a single infusion. If they have a partial response or receive therapy post-infusion which could ablate the infused T cells they are eligible to receive up to 2 additional doses from 28 days after their first dose.
干预措施: Pentavalent-specific T cells (penta-STs) (Biological)
结局指标
主要结局
Acute GvHD
时间窗: Within 6 weeks post the last dose of penta-STs
The safety of cell therapy with penta-STs will be assessed according to acute and chronic GvHD grades III-IV
Chronic GvHD
时间窗: Within 6 months post the last dose of penta-STs
The safety of cell therapy with penta-STs will be assessed according to acute and chronic GvHD grades III-IV
Infusion-related adverse events
时间窗: Within 30 days of the last dose of penta-STs
The safety of cell therapy with penta-STs will be assessed according to grades ≥3 infusion-related adverse events
Non hematological, adverse events
时间窗: Within 30 days of the last dose of penta-STs
The safety of cell therapy with penta-STs will be assessed according to grades ≥3 non hematological, adverse events within 30 days of the last penta-ST dose, which are not due to the preexisting infection/comorbidities or the original malignancy
Resolution of infection - 1
时间窗: 12 weeks post the last dose of penta-STs
The efficacy of penta-STs will be determined based on the reduction/elimination of pathogen load in patients with infections
Resolution of infection - 2
时间窗: 12 weeks post the last dose of penta-STs
The efficacy of penta-STs will be determined based on the amelioration/elimination of clinical symptoms in patients with viral disease
Antiviral immunity
时间窗: 12 weeks post the last dose of penta-STs
The efficacy of penta-STs will be determined based on the reconstitution of antiviral immunity (determination of virus-specific T cells)
Antifungal immunity
时间窗: 12 weeks post the last dose of penta-STs
The efficacy of penta-STs will be determined based on reconstitution of antifungal immunity (determination of Aspergillus fumigatus-specific T cells)
Viral reactivations or recurrence of AF infection
时间窗: 6 months post the last dose of penta-STs
The efficacy of penta-STs will be determined by the absence of viral reactivations or recurrence of AF infection post penta-STs infusion
次要结局
未报告次要终点
研究者
Evangelia Yannaki
PI, Director of the Gene and Cell Therapy Center, Hematology-HCT Unit
George Papanicolaou Hospital