CurePML - Allogeneic HPyV-2-specific T-cell Therapy in Patients With Progressive Multifocal Leukoencephalopathy
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 23
- 试验地点
- 6
- 主要终点
- Demonstrate efficacy of treatment
研究概览
简要总结
There is no approved standard treatment für progressive multifocal leukoencephalopathy (PML). The sponsor of the study is developing a new treatment. For this reason, the investigational medicinal product (IMP) called 'human allogenic HPyV-2-specific T cells' is to be tested in this study. The sponsor wants to find out whether the IMP is safe, influences the neurological status and improves the quality of the life of patients . It is to be investigated whether the IMP can be used to treat the disease and whether it could have an advantage over the standard therapy in terms of survival rate.
详细描述
Progressive multifocal leukoencephalopathy (PML) is a severe infection of the central nervous system (CNS) caused by reactivation of human polyoma virus 2 (HPyV-2). HPyV-2 usually produces asymptomatic, lifelong persistent or latent infection in the general population. However, in patients with long lasting and profound impairment of cellular immunity, HPyV-2 can reactivate from latency leading to lytic infection of CNS glial cells and thus to encephalitis PML. PML is usually fatal or at least associated with severe disability which makes it a relevant target for the search of appropriate therapeutic options.
The investigational medicinal products (IMPs) under test are fresh and cryopreserved allogeneic HPyV-2-specific T-lymphocyte apheresis concentrates.
Each patient will receive one HPyV-2-specific T-lymphocyte fresh product and two additional cryopreserved products from the same manufacture with the same dose 2 and 6 weeks after baseline, respectively.
This is the first controlled clinical trial to treat patients suffering from PML with this specific methodology of T-cell therapy. The currently available evidence of safety and efficacy is only based on a small series of individual cases treated on a compassionate use basis. This study aims to generate data on safety and first evidence of efficacy within a standardized clinical trial protocol complying to ICH-GCP principles.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults* aged ≥ 18 years with PML (diagnosed ≤ 60 days before screening) associated with one or more of the following risk factors: lymphoproliferative diseases, immunosuppressive therapy, or lymphopenia
- •Signed written informed consent from subject and/or legal representative
- •HPyV-2 detection in CSF by PCR analysis or in brain biopsy
排除标准
- •PML caused by HIV
- •PML caused by natalizumab
- •PML occurring within five 5 years after hematopoietic stem-cell transplantation or CAR T cell therapy, or resulting from chronic lymphocytic leukemia (CLL)
- •Patients who are unable to follow the study protocol, either on their own or with the support of a reliable representative, will be excluded
- •Pregnancy or breastfeeding
- •Currently receiving chemotherapy
- •Present (within 2 weeks before screening visit) and continuous treatment with immune checkpoint inhibition therapy
- •Severe infections other than PML (e.g. sepsis, pneumonia)
- •Hypersensitivity to any of the components of the medications used
- •Inability to undergo MRI examination (e.g. implanted incompatible medical devices, claustrophobia)
- •Participation in another clinical trial (other investigational drugs or devices at the time of enrolment or within 30 days prior to enrolment)
研究组 & 干预措施
Intervention
Study participants receive complete or partially HLA-matched, allogeneic HPyV-2-specific T-lymphocytes
干预措施: Application of T-lymphocytes (Drug)
结局指标
主要结局
Demonstrate efficacy of treatment
时间窗: 6 months after diagnosis
Determine proportion of patients surviving 6 months (overall survival) since diagnosis.
次要结局
- Safety assessment(At 12 months from baseline)
- Safety assessment of potential electrolyte imbalance(During 6 months from baseline)
- Rate of development of IRIS(During 6 months from baseline)
- Assessment of neurological status by Modified Rankin Scale (mRS)(Change from baseline after 6 months)
- Assessment of neurological status by Karnofsky Performance Status Index(Change from baseline after 6 months)
- Assessment of neurological status by Montreal Cognitive Assessment (MoCA)(Change from baseline after 6 months)
- Determine change in viral load(Change from baseline after 6 months)
- Evaluation of quality of life improvements by quality of life questionnaire (EQ-5D-5L)(Change from baseline after 6 months)
- Analysis of immunological response(Change from baseline after 6 months)
- Determine lesion volume(Change from baseline after 6 months)
- Evaluation of survival(At month 12)
- Assessment of potential inflammatory safety concerns(During 6 months from baseline)
- Safety assessment of potential renal dysfunction(During 6 months from baseline)
- Safety assessment of potential liver dysfunction(During 6 months from baseline)
- Safety assessment of potential coagulation disorder(During 6 months from baseline)
- Safety assessment(During 12 months from baseline)