CD45RA-depleted DLI for the Prevention of Viral Infections in High-risk Patients After Haploidentical Transplantation (CD45RADLIPx)
CD45RA-depleted DLI for the Prevention of Viral Infections in High-risk Patients After Transplantation: a Prospective, Multicenter, Single-arm, Pragmatic Clinical Study
The goal of this clinical trial is to learn whether giving patients a special type of donor immune cells (called CD45RA Depleted DLI) can help prevent viral infections after a stem cell transplant. It will also learn about the safety of this treatment. The main questions it aims to answer are:
Does this treatment lower the chance of getting serious viral infections after transplant? What medical problems do patients have when receiving this treatment?
研究概览
详细说明
Following allogeneic hematopoietic stem cell transplantation (allo-HSCT), delayed immune reconstitution and long-term use of immunosuppressants leave patients in a prolonged immunocompromised state, predisposing them to various infections, which represent a leading cause of transplant-related mortality. Conventional antiviral agents such as ganciclovir and valganciclovir are associated with hematologic toxicities, including neutropenia and anemia, potentially complicating post-transplant management. Meanwhile, newer antivirals such as cidofovir have not yet been approved in China, limiting patient access. Antiviral cell therapies, represented by virus-specific T cells (VSTs), are expensive and require prolonged culture periods. Therefore, there is an urgent need to identify effective strategies to prevent viral infections after HSCT, especially in high-risk patients.
Previous studies suggest that adoptive donor lymphocyte infusion (DLI) can facilitate immune reconstitution; however, the CD45RA-positive naïve T cells contained in conventional DLI are a major cause of graft-versus-host disease (GvHD). By depleting naïve T cells from donor lymphocytes ex vivo while retaining donor memory T cells (Tm), it is possible to promote post-transplant immune reconstitution without increasing the risk of GvHD. This study plans to conduct a prospective, multicenter, single-arm pragmatic clinical trial. Using the CliniMACS® cell selection system, we will selectively deplete CD45RA-positive T cells ex vivo and infuse the CD45RA-depleted donor lymphocytes (i.e., CD45RA Depleted DLI) to prevent viral infections in high-risk patients after transplantation. The efficacy, safety, and impact on post-transplant immune reconstitution of this regimen will be evaluated.
Primary objective: To evaluate the efficacy and safety of CD45RA Depleted DLI in preventing viral infections in high-risk patients after transplantation.
Secondary objective: To evaluate the impact of CD45RA Depleted DLI on immune reconstitution after transplantation.
研究类型
注册 (估计的)
阶段
- 阶段1
联系人和位置
学习地点
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SH
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Shanghai、SH、中国、200025
- Ruijin Hospital
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接触：
- Xiaoxia Hu, MD, PhD
- 电话号码：008613795437259
- 邮箱：hu_xiaoxia@126.com
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参与标准
资格标准
适合学习的年龄
- 孩子
- 成人
接受健康志愿者
描述
Inclusion Criteria:
Participants must meet all of the following criteria:
- Patients undergoing allogeneic hematopoietic stem cell transplantation (any conditioning regimen or graft source is allowed).
- Presence of at least one high-risk factor for post-transplant viral infection (any of the following):
- Age ≥50 years or ≤14 years
- Non-sibling matched transplantation
- In vivo or ex vivo T-cell depletion
- Myeloablative conditioning
- Conditioning containing radiotherapy
- Second transplantation
- CMV IgG or EBV IgG donor/recipient mismatch (donor positive, recipient negative)
- History of grade II or higher acute graft-versus-host disease (aGVHD) after transplantation and use of high-dose corticosteroids (prednisone equivalent ≥1 mg/kg/day)
- Availability of a suitable lymphocyte donor (see "Donor Selection Criteria").
- Adequate organ function meeting the following laboratory criteria:
- Liver function: ALT and AST ≤10× upper limit of normal (ULN); total bilirubin ≤5× ULN
- Renal function: BUN and creatinine ≤1.25× ULN
- No cardiac dysfunction on electrocardiogram or echocardiogram
- Pulmonary function: oxygen saturation >90% without supplemental oxygen
- The patient or legal guardian has the desire and request to receive treatment, signs the informed consent form before treatment, and is willing to comply with the treatment plan, follow-up schedule, and laboratory tests.
Exclusion Criteria:
Patients meeting any of the following criteria will be excluded from this study:
- Active grade II-IV acute graft-versus-host disease (aGVHD)
- Active aGVHD requiring prednisone or equivalent corticosteroid >0.5 mg/kg/day
- Active viral infection
- Uncontrolled or relapsed malignancy
- Other serious acute or chronic physical or psychiatric conditions, or laboratory abnormalities, that may compromise patient safety or compliance, or affect informed consent, study participation, follow-up, or interpretation of results.
学习计划
研究是如何设计的？
设计细节
- 主要用途：预防
- 分配：不适用
- 介入模型：单组作业
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
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实验性的：Prevention Group
Prophylactic CD45RA-depleted DLI
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CD45RA Depleted DLI by ex vivo CliniMACS® prepared from mononuclear cell leukapheresis
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Cumulative Incidence of Overall Viral Infection After CD45RA-Depleted DLI
大体时间：Up to 3 months after the first CD45RA-depleted DLI, assessed at Days 14, 28, 60, and 90.
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Overall viral infection is defined as the first occurrence of any qualifying viral infection or reactivation detected by quantitative PCR after the first CD45RA-DLI infusion. Viruses assessed include CMV, EBV, ADV, BKV, HHV6, JCV, and B19. A participant will be considered to have a qualifying viral event if any of the following thresholds are met: CMV DNA ≥250 IU/mL, EBV DNA ≥250 IU/mL, ADV DNA ≥1,000 copies/mL, BKV DNA ≥5,000 copies/mL, HHV6 DNA ≥1,000 copies/mL, JCV DNA ≥1,000 copies/mL, or B19 DNA ≥1,000 copies/mL. The outcome will be reported as the cumulative incidence, expressed as the percentage of participants with at least one qualifying viral infection or reactivation event during the assessment period. |
Up to 3 months after the first CD45RA-depleted DLI, assessed at Days 14, 28, 60, and 90.
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Cumulative Incidence of Virus-Specific Infections After CD45RA-Depleted DLI
大体时间：Up to 3 months after first infusion
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Report cumulative incidence separately for CMV, EBV, ADV, BKV, HHV6, JCV, and B19 using the protocol-defined PCR thresholds.
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Up to 3 months after first infusion
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Absolute Counts of Peripheral Blood Lymphocyte Subsets as Measured by Flow Cytometry
大体时间：Up to 1 year after the first CD45RA-depleted DLI
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Immune reconstitution will be assessed by flow cytometric enumeration of peripheral blood lymphocyte subsets, including CD3+ T cells, CD4+ T cells, CD8+ T cells, CD19+ B cells, CD56+ NK cells, and CD4+CD25+CD127- regulatory T cells.
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Up to 1 year after the first CD45RA-depleted DLI
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Virus-Specific T-Cell Immune Responses After CD45RA-Depleted DLI
大体时间：Up to 3 months after the first CD45RA-depleted DLI, assessed at Days 14, 28, 60, and 90.
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Virus-specific immune reconstitution will be assessed by measuring virus-specific T-cell responses against CMV, EBV, ADV, BKV, B19, HHV6, and JCV using the protocol-defined virus-specific T-cell assay.
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Up to 3 months after the first CD45RA-depleted DLI, assessed at Days 14, 28, 60, and 90.
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合作者和调查者
研究记录日期
研究主要日期
学习开始 (估计的)
初级完成 (估计的)
研究完成 (估计的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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