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
Přehled studie
Postavení
Intervence / Léčba
Detailní popis
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.
Typ studie
Zápis (Odhadovaný)
Fáze
- Fáze 2
- Fáze 1
Kontakty a umístění
Studijní kontakt
- Jméno: Xiaoxia Hu, MD, PhD
- Telefonní číslo: 008613795437259
- E-mail: hu_xiaoxia@126.com
Studijní místa
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SH
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Shanghai, SH, Čína, 200025
- Nábor
- Ruijin Hospital
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Kontakt:
- Xiaoxia Hu, MD, PhD
- Telefonní číslo: 008613795437259
- E-mail: hu_xiaoxia@126.com
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-
Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
- Dítě
- Dospělý
- Starší dospělý
Přijímá zdravé dobrovolníky
Popis
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.
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: N/A
- Intervenční model: Přiřazení jedné skupiny
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
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Experimentální: Treatment Group
CD45RA Depleted DLI
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CD45RA depleted donor lymphocyte infusion (DLI) admission with escalated dose
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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Percentage of Participants Achieving Overall Response of Viral Infection Based on Quantitative PCR and Clinical Response Criteria
Časové okno: 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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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Virus-specific T-cell Response
Časové okno: 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
Časové okno: 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
Časové okno: 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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Spolupracovníci a vyšetřovatelé
Sponzor
Spolupracovníci
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Odhadovaný)
Primární dokončení (Odhadovaný)
Dokončení studie (Odhadovaný)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Další relevantní podmínky MeSH
Další identifikační čísla studie
- RJ-BMT-Infection 1.0
Plán pro data jednotlivých účastníků (IPD)
Plánujete sdílet data jednotlivých účastníků (IPD)?
Popis plánu IPD
Informace o lécích a zařízeních, studijní dokumenty
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Studuje produkt zařízení regulovaný americkým úřadem FDA
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