Ex Vivo CD45RA-depleted DLI for the Treatment of Refractory/Persistent Viral Infections After Transplantation: a Prospective, Multicenter, Single-arm, Pragmatic Clinical Study
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Percentage of Participants Achieving Overall Response of Viral Infection Based on Quantitative PCR and Clinical Response Criteria
研究概览
简要总结
The goal of this clinical trial is to learn whether giving patients special donor immune cells (called "CD45RA Depleted DLI") can help treat viral infections that have not improved with standard antiviral drugs. These infections occur after a stem cell transplant. The study will also look at the safety of this treatment.
详细描述
Due to delayed immune reconstitution and long-term use of immunosuppressants after allogeneic hematopoietic stem cell transplantation, patients remain in a state of prolonged immunocompromise and are prone to various infections, which is one of the leading causes of death after transplantation. The overall response rate of various antiviral drugs ranges from 60% to 80%, meaning 20-40% of patients cannot be effectively treated. Moreover, most antiviral agents have significant toxicities that patients often cannot tolerate. Therefore, finding appropriate and effective antiviral therapeutic strategies is urgently needed for transplant recipients.
Previous studies have indicated that adoptive donor lymphocyte infusion (DLI) can help reconstitute immunity; however, the CD45RA-positive naïve T cells contained in DLI are a major cause of graft-versus-host disease (GVHD). By ex vivo selection to deplete naïve T cells from donor lymphocytes while retaining donor memory T cells (Tm), it may be possible to promote immune reconstitution, clear viral infections, improve the cure rate of viral infections, and reduce the incidence of GVHD. This study is planned as a prospective, multicenter, single-arm, pragmatic clinical trial. We intend to use the CliniMACS® cell selection system to selectively deplete CD45RA-positive T cells ex vivo and infuse the selected donor lymphocytes (DLI) to treat viral infections that are refractory to first-line therapy after hematopoietic stem cell transplantation. We will evaluate the efficacy and safety of this treatment for post-transplant viral infections, as well as its impact on immune reconstitution after transplantation.
Study Objectives:
Primary objective: To evaluate the efficacy and safety of CD45RA Depleted DLI for the treatment of refractory/persistent viral infections after transplantation.
Secondary objective: To evaluate the effect of CD45RA Depleted DLI on the reconstitution of virus-specific T cell (VST) immunity after transplantation.
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
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must meet all of the following criteria:
- •Patients who have undergone hematopoietic stem cell transplantation.
- •Presence of viremia and/or viral infection-related disease caused by a single virus or multiple viruses among the following: CMV, EBV, ADV, BK, B19, JC, HHV-6B, HSV1, or HSV
- •Patients who, after ≥2 weeks of first-line therapy, have persistent viral positivity, no relief or worsening of clinical symptoms, or re-infection with the same pathogen after viral clearance.
- •Availability of a suitable lymphocyte donor.
- •Adequate organ function, meeting the following laboratory criteria:
- •Liver function: ALT and AST ≤ 10 × upper limit of normal (ULN), TBIL ≤ 5 × ULN.
- •Renal function: BUN and Cr ≤ 1.25 × ULN.
- •No cardiac insufficiency on electrocardiogram (ECG) or echocardiogram.
- •Pulmonary function: oxygen saturation > 90% on room air.
- •Willingness and ability of the patient or their legal guardian to receive treatment, comply with the treatment plan, follow-up schedule, and laboratory examinations, and provision of signed informed consent before any study-specific procedure.
排除标准
- •Patients meeting any of the following criteria will be excluded from this study:
- •Active grade II-IV acute graft-versus-host disease (aGVHD).
- •Prednisone or equivalent corticosteroid dose > 0.5 mg/kg/day.
- •Receipt of anti-thymocyte globulin (ATG), alemtuzumab (Campath), or other T-cell immunosuppressive monoclonal antibodies within 28 days before enrollment.
- •Less than 28 days after allogeneic transplantation, or receipt of donor lymphocyte infusion (DLI) or virus-specific T cell (VST) therapy within 28 days before enrollment.
- •Uncontrolled or relapsed malignancy.
- •Presence of other serious acute or chronic physical or psychiatric conditions, or laboratory abnormalities, that may compromise patient safety or compliance, or that may interfere with informed consent, study participation, follow-up, or interpretation of study results.
研究组 & 干预措施
Treatment Group
CD45RA Depleted DLI
干预措施: CD45RA depleted donor lymphocyte infusion (DLI) (Biological)
结局指标
主要结局
Percentage of Participants Achieving Overall Response of Viral Infection Based on Quantitative PCR and Clinical Response Criteria
时间窗: 90 days after the first CD45RA-depleted donor lymphocyte infusion
Overall response rate is defined as the percentage of participants who achieve complete response or partial response after CD45RA-depleted DLI. Complete response is defined as negative viral PCR together with disappearance of all virus-related clinical signs and symptoms. Partial response is defined as at least a 50% reduction in viral load from baseline together with at least 1-grade improvement in clinical symptoms. Overall response rate will be calculated as the number of participants with complete response or partial response divided by the total number of evaluable participants.
次要结局
- Virus-specific T-cell Response(90 days after the first CD45RA-depleted DLI)
- Grade III-IV Acute Graft-versus-Host Disease(90 days after the first CD45RA-depleted DLI)
- Chronic Graft-versus-Host Disease(Up to 1 years after CD45RA-depleted DLI)