A Pilot Study of Adoptive Cellular Immunotherapy for Progressive Multifocal Leukoencephalopathy With Ex Vivo Generated Polyomavirus-Specific T-cells
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Characterization of the safety and feasibility of PyVST infusion for the treatment of PML based on development of Treatment Limiting Toxicity
研究概览
简要总结
Background:
Progressive Multifocal Leukoencephalopathy (PML) is a brain infection in people with a weakened immune system. Researchers think polyoma virus specific T cells (PyVST) therapy can treat PML. The PyVST cells are made from blood cells of a healthy relative. They are grown in a lab to expand the virus-killing cells, then given to the person with PML.
Objective:
To test whether PyVST safely treats PML.
Eligibility:
-
Adults ages 18 and older with PML
-
Healthy adults ages 18 and older who have:
-
Been screened under protocol 97-H-0041
-
A sibling, parent, or child with PML and matching cells
Design:
-
Participants will be screened with:
-
Medical history
-
Physical exam
-
Blood and urine tests
-
PML participants will also be screened with:
-
Cerebrospinal fluid removed by needle in the back.
-
MRI: A dye is injected in a vein. They lie on a table that slides into a cylinder.
-
Questionnaires
Healthy participants will have apheresis: Blood flows through a needle in one arm into machine that separates blood cells needed for donation. The rest of the blood is returned by needle to the other arm. Some participants may have a central line placed in a vein instead. They can have apheresis up to 3 times, at least 28 days apart.
Participants with PML will receive the PyVST cells by needle in the arm. They will stay in the hospital 1 week. They can do this up to 3 times, at least 28 days apart. After each infusion, they will have weekly visits for 1 month. Then they will have 4 visits over 1 year. Visits include repeats of screening tests.
详细描述
Objective
This pilot clinical trial will aim to determine the feasibility and potential toxicities associated with treating patients with progressive multifocal leukoencephalopathy (PML) with polyomavirus (PyV)-specific partially matched polyclonal allogeneic T cells. It will further provide initial efficacy data for this indication.
Study Population
Up to 18 subjects with definite PML, defined as clinical signs and MRI compatible with active PML and the presence of JCV by PCR in CSF. Subjects must be 18 years of age or older and must have a first degree, partially HLA- matched relative able and willing to act as a donor of lymphocytes. Subjects with underlying reversible immunosuppression (i.e.- HIV or MS status post treatment with natalizumab), or subjects with uncontrolled malignancy will be excluded. Subjects with evidence of active CNS inflammation as determined by presence of significant contrast enhancement within the PML lesions by MRI will also be excluded because it is assumed such patients are already mounting an adequate immune response against the infection.
Design
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
- •INCLUSION CRITERIA - PATIENT:
- •Clinically definite PML, defined as clinical signs and MRI compatible with active PML and the presence of JCV by PCR in CSF
- •Modified Rankin Scale 1-4, inclusive
- •Age 18 or older
- •Patient medically stable and able to tolerate travel to NIH
- •Available PyVST
- •Subjects of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while they are being treated on this study
- •Willing and able to participate in all aspects of trial design and follow-up
- •Able to provide informed consent at the time of study enrollment (not required for reinfusions).
排除标准
- •Patients with human immunodeficiency virus (HIV infection)
- •Patients who have been treated with natalizumab
- •Patients with readily reversible immunosuppressive state
- •Patients receiving immunosuppressive or immunomodulatory therapies within 28 days of screening for enrollment that could interfere with PyVST function
- •Patients with other uncontrolled infections. For bacterial infections, patients must be receiving definitive therapy and have no signs of progressing infection for 72 hours prior to enrollment. For fungal infections, patients must be receiving definitive systemic anti-fungal therapy and have no signs of progressing infection for 1 week prior to enrollment.
- •Patients who have received donor lymphocyte infusion (DLI) within 28 days
- •Uncontrolled relapse of malignancy
- •Patients with any other associated CNS disease that might confound outcomes
- •Patients with contraindication to MRI (including cardiac pacemakers and some infusion pumps, other metallic implants, metallic foreign objects)
- •MRI findings consistent with immune system reconstitution inflammatory syndrome (IRIS) and determined to be mounting an adequate immune response to the infection
- •Patients with medical contraindication to LP
- •For subjects who have previously received PyVST infusions, any treatment-limiting toxicity (defined in Section 8.3) to previous infusions
- •Subjects with a positive pregnancy test or who are nursing.
- •INCLUSION CRITERIA - DONOR:
- •Ability to provide informed consent at the time of enrollment
- •First degree relative of patient (sibling, parent/child)
- •Age 18 or older
- •EXCLUSION CRITERIA - DONOR:
- •Sickling hemoglobinopathies including HbSS and HbSC by history and peripheral blood smear; donors with HbAS are acceptable
- •HbsAg, anti-HBc, anti-HCV, anti-HIV, anti-HTLV, and RPR
- •Cardiovascular instability, severe anemia, inadequate venous access, severe coagulation disorder or any other medical condition that the Principal Investigator or Apheresis Unit staff considers a contraindication to the apheresis procedure or research blood draw.
- •Positive pregnancy test
研究组 & 干预措施
Treatment Arm
ex vivo generated polyomavirus-specific T cells from HLA-matched donor
干预措施: PyVST (Biological)
结局指标
主要结局
Characterization of the safety and feasibility of PyVST infusion for the treatment of PML based on development of Treatment Limiting Toxicity
时间窗: ongoing
Characterization of the safety and feasibility of PyVST infusion for the treatment of PML based on development of Treatment Limiting Toxicity
次要结局
- PML lesion volume(change from baseline to day 28)
- Gadolinium enhancement(Change in pattern of gadolinium enhancement from baseline to day 3, day 7, day 14, and day 28)
- Modified Rankin Score(Change from baseline to day 28)
- JC viral load in CSF(Change from baseline to day 28)