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?
Tutkimuksen yleiskatsaus
Tila
Interventio / Hoito
Yksityiskohtainen kuvaus
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.
Opintotyyppi
Ilmoittautuminen (Arvioitu)
Vaihe
- Vaihe 1
Yhteystiedot ja paikat
Opiskelupaikat
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SH
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Shanghai, SH, Kiina, 200025
- Ruijin Hospital
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Ottaa yhteyttä:
- Xiaoxia Hu, MD, PhD
- Puhelinnumero: 008613795437259
- Sähköposti: hu_xiaoxia@126.com
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Osallistumiskriteerit
Kelpoisuusvaatimukset
Opintokelpoiset iät
- Lapsi
- Aikuinen
Hyväksyy terveitä vapaaehtoisia
Kuvaus
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.
Opintosuunnitelma
Miten tutkimus on suunniteltu?
Suunnittelun yksityiskohdat
- Ensisijainen käyttötarkoitus: Ennaltaehkäisy
- Jako: Ei käytössä
- Inventiomalli: Yksittäinen ryhmätehtävä
- Naamiointi: Ei mitään (avoin tarra)
Aseet ja interventiot
Osallistujaryhmä / Arm |
Interventio / Hoito |
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Kokeellinen: 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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Mitä tutkimuksessa mitataan?
Ensisijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
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Cumulative Incidence of Overall Viral Infection After CD45RA-Depleted DLI
Aikaikkuna: 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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Toissijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
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Cumulative Incidence of Virus-Specific Infections After CD45RA-Depleted DLI
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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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Yhteistyökumppanit ja tutkijat
Sponsori
Yhteistyökumppanit
Opintojen ennätyspäivät
Opi tärkeimmät päivämäärät
Opiskelun aloitus (Arvioitu)
Ensisijainen valmistuminen (Arvioitu)
Opintojen valmistuminen (Arvioitu)
Opintoihin ilmoittautumispäivät
Ensimmäinen lähetetty
Ensimmäinen toimitettu, joka täytti QC-kriteerit
Ensimmäinen Lähetetty (Todellinen)
Tutkimustietojen päivitykset
Viimeisin päivitys julkaistu (Todellinen)
Viimeisin lähetetty päivitys, joka täytti QC-kriteerit
Viimeksi vahvistettu
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