CD45RA-depleted DLI for the Treatment of Refractory/Persistent Viral Infections After Haploidentical Transplantation (CD45RADLITx)
Ex Vivo CD45RA-depleted DLI for the Treatment of Refractory/Persistent Viral Infections After Transplantation: a Prospective, Multicenter, Single-arm, Pragmatic Clinical Study
연구 개요
상태
상태
정황
정황
개입 / 치료
개입 / 치료
상세 설명
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.
연구 유형
연구 유형
등록 (추정된)
등록
단계
단계
- 2 단계
- 1단계
연락처 및 위치
연구 연락처
연구 연락처
- 이름: Xiaoxia Hu, MD, PhD
- 전화번호: 008613795437259
- 이메일: hu_xiaoxia@126.com
연구 장소
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SH
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Shanghai, SH, 중국, 200025
- 모병
- Ruijin Hospital
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연락하다:
- Xiaoxia Hu, MD, PhD
- 전화번호: 008613795437259
- 이메일: hu_xiaoxia@126.com
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-
참여기준
자격 기준
자격 기준
공부할 수 있는 나이
- 어린이
- 성인
- 고령자
건강한 자원 봉사자를 받아들입니다
설명
Inclusion Criteria:
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 HSV2.
- 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.
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).
- 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.
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 해당 없음
- 중재 모델: 단일 그룹 할당
- 마스킹: 없음(오픈 라벨)
팔의 수
무기와 개입
참가자 그룹 / 팔참가자 그룹 / 팔 |
개입 / 치료개입 / 치료 |
|---|---|
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실험적: Treatment Group
CD45RA Depleted DLI
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CD45RA depleted donor lymphocyte infusion (DLI) admission with escalated dose
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연구는 무엇을 측정합니까?
주요 결과 측정
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Percentage of Participants Achieving Overall Response of Viral Infection Based on Quantitative PCR and Clinical Response Criteria
기간: 90 days after the first CD45RA-depleted donor lymphocyte infusion
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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. |
90 days after the first CD45RA-depleted donor lymphocyte infusion
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2차 결과 측정
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Virus-specific T-cell Response
기간: 90 days after the first CD45RA-depleted DLI
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Virus-specific T-cell response will be assessed in peripheral blood using the protocol-specified virus-specific T-cell assay.
The assessment may include virus-specific T-cell responses against clinically relevant protocol-specified viruses, including CMV, EBV, adenovirus, BK virus, B19, HHV-6, and JC virus, as applicable to each participant's viral infection.
The outcome will summarize the change from baseline in virus-specific T-cell response after CD45RA-depleted DLI.
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90 days after the first CD45RA-depleted DLI
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Grade III-IV Acute Graft-versus-Host Disease
기간: 90 days after the first CD45RA-depleted DLI
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This outcome will measure the percentage of participants who develop new-onset Grade III-IV acute graft-versus-host disease after CD45RA-depleted DLI.
Acute GVHD will be assessed and graded according to MAGIC criteria.
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90 days after the first CD45RA-depleted DLI
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Chronic Graft-versus-Host Disease
기간: Up to 1 years after CD45RA-depleted DLI
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This outcome will measure the percentage of participants who develop chronic graft-versus-host disease after CD45RA-depleted DLI.
Chronic GVHD will be assessed and graded according to NIH 2014 criteria, including mild, moderate, and severe chronic GVHD.
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Up to 1 years after CD45RA-depleted DLI
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공동 작업자 및 조사자
협력자
협력자
연구 기록 날짜
연구 주요 날짜
연구 시작 (추정된)
연구 시작
기본 완료 (추정된)
기본 완료
연구 완료 (추정된)
연구 완료
연구 등록 날짜
최초 제출
최초 제출
QC 기준을 충족하는 최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
처음 게시됨
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
마지막 업데이트 게시됨
QC 기준을 충족하는 마지막 업데이트 제출
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
기타 연구 ID 번호
기타 연구 ID 번호
- RJ-BMT-Infection 1.0
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
IPD 계획 설명
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
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