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Immunological Reset to Enable Access to Hla-compatible Kidney Transplantation in Highly Sensitized Patients (RESET) (HIPER-RESET)

2 juin 2026 mis à jour par: Hospital Universitari Vall d'Hebron Research Institute

Immune Reset to Allow Access to Hla-compatible Kidney Transplantation in Hyperimmunized Patients

The purpose of this clinical trial is to evaluate whether a temporary reprogramming of the immune system can help highly sensitized (hyperimmunized) patients with end-stage kidney disease safely receive a compatible kidney transplant.

Patients who are highly sensitized have developed an extremely high level of antibodies against human leukocyte antigens (HLA), often due to previous transplants, pregnancies, or blood transfusions. This condition makes it nearly impossible for them to find a compatible organ donor, leaving them stuck on dialysis indefinitely.

This study tests an innovative strategy using Autologous Hematopoietic Stem Cell Transplantation (AHSCT). The procedure involves an intensive conditioning regimen using a combination of medications (cyclophosphamide, thymoglobulin, and rituximab) to deeply clear out the patient's existing mature immune cells. This is followed by the reinfusion of the patient's own previously collected and purified blood stem cells (CD34+ cells) to rebuild the immune system from scratch.

The investigators hypothesize that this procedure will eliminate the "immunological memory" cells responsible for producing the problematic anti-HLA antibodies, resetting the immune system to a "naive" or inactive state. This immune reset is expected to eliminate or significantly lower circulating HLA antibodies, creating a critical window of opportunity for these patients to successfully receive a compatible kidney transplant from the deceased-donor waiting list.

Aperçu de l'étude

Statut

Recrutement

Les conditions

Intervention / Traitement

Description détaillée

This single-center, open-label, non-randomized phase Ib/II pilot study will evaluate the safety, feasibility, and immunological effects of autologous hematopoietic stem cell transplantation (AHSCT) in highly sensitized patients awaiting kidney transplantation.

A total of 10 hyperimmunized patients on the kidney transplant waiting list will be enrolled in two sequential phases. In Phase 1, four participants will undergo AHSCT with close safety monitoring during a 12-month follow-up period. In the absence of severe adverse events, participants will be reactivated on the deceased-donor kidney transplant waiting list at 6 months post-AHSCT. Following safety evaluation of the initial cohort, an additional six participants will be enrolled in Phase 2 to further assess the efficacy and safety of the strategy.

The intervention includes a non-myeloablative lymphodepletion and stem cell mobilization regimen followed by collection, CD34+ selection, and reinfusion of autologous hematopoietic progenitor cells. After AHSCT, eligible participants may undergo deceased-donor kidney transplantation following confirmation of HLA compatibility by standard crossmatch techniques.

Kidney transplant recipients will receive standard-of-care induction and maintenance immunosuppressive therapy according to institutional clinical practice.

The study also includes longitudinal immunological monitoring to characterize adaptive immune reconstitution and anti-HLA responses after AHSCT and kidney transplantation. Peripheral blood and bone marrow samples will be collected at predefined time points to evaluate T- and B-cell memory compartments, donor-specific antibodies, and pathogen-specific immune responses.

Primary objectives include assessment of safety and feasibility, as well as evaluation of changes in sensitization status and access to HLA-compatible kidney transplantation following AHSCT.

Type d'étude

Interventionnel

Inscription (Estimé)

10

Phase

  • Phase 2
  • La phase 1

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Coordonnées de l'étude

Lieux d'étude

  • Espagne
    • Catalonia
      • Barcelona, Catalonia, Espagne, 08035
        • Recrutement
        • Hospital Universitari Vall d'Hebron
        • Contact:
        • Chercheur principal:
          • Oriol Bestard, Nephrologist

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

  • Adulte

Accepte les volontaires sains

Non

La description

Inclusion Criteria:

  • Patients aged between 18 and 60 years.
  • Diagnosis of end-stage kidney disease (ESRD) currently maintained on chronic dialysis.
  • Highly sensitized/hyperimmunized status, defined by a high calculated Panel Reactive Antibody (cPRA) level (e.g., >= 95%).
  • Active status on the deceased-donor kidney transplant waiting list.
  • Adequate bone marrow, hepatic, cardiac, and pulmonary function to safely undergo the conditioning regimen and AHSCT.
  • Capable of understanding the study requirements and providing written informed consent.

Exclusion Criteria:

  • Contraindications to the conditioning regimen medications (rituximab, cyclophosphamide, or rATG).
  • Active, uncontrolled systemic infection, or chronic active infection (including HIV, active Hepatitis B or C, or active tuberculosis).
  • Significant cardiac dysfunction (e.g., Left Ventricular Ejection Fraction < 50%) or severe underlying pulmonary disease.
  • History of malignant neoplasm within the past 5 years, excluding successfully treated non-melanoma skin cancer or carcinoma in situ.
  • Previous autologous or allogeneic hematopoietic stem cell transplantation.
  • Pregnancy or breastfeeding.
  • Any psychiatric, medical, or geographical condition that, in the investigator's opinion, prevents compliance with the protocol and long-term follow-up.

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: N / A
  • Modèle interventionnel: Affectation à un seul groupe
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: Autologous Hematopoietic Stem Cell Transplantation (AHSCT)
Participants undergo a non-myeloablative conditioning regimen for intense lymphodepletion consisting of intravenous Rituximab, Cyclophosphamide (adjusted for end-stage renal disease), and Thymoglobulin (rATG). This is followed by peripheral blood stem cell collection via leukapheresis, CD34+ immunomagnetic selection, and the reinfusion of purified autologous CD34+ progenitors (target dose >= 3 x 10⁶ cells/kg). At 6 months post-AHSCT, patients are reactivated on the deceased-donor kidney transplant waiting list.
Biologique: Autologous Hematopoietic Stem Cell Transplantation
A comprehensive cell therapy protocol involving intense non-myeloablative lymphodepletion followed by stem cell rescue. The intervention includes sequential intravenous administration of Rituximab, Cyclophosphamide (specifically dose-adjusted for end-stage renal disease), and rabbit Thymoglobulin (rATG). Following conditioning, participants receive an intravenous reinfusion of purified autologous CD34+ hematopoietic progenitor cells collected via peripheral blood leukapheresis at a target dose of >= 3 x 10⁶ cells/kg, with a cryopreserved backup aliquot maintained for safety.
Autres noms:
  • AHSCT
  • Autologous CD34+ stem cell infusion

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Incidence of Treatment-Emergent Adverse Events (Safety Profile)
Délai: From baseline up to 12 months post-AHSCT.
Evaluation of the safety and tolerability of the intense conditioning regimen and autologous hematopoietic stem cell transplantation (AHSCT). This includes monitoring the number, severity, and type of serious and non-serious adverse events, evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE).
From baseline up to 12 months post-AHSCT.
Change in Calculated Panel Reactive Antibody (cPRA) Levels
Délai: Baseline compared to 6 months post-AHSCT (at the time of re-listing).
Assessment of changes in circulating anti-HLA antibodies following the AHSCT protocol, measured by calculated Panel Reactive Antibody (cPRA) levels compared to baseline. Changes in cPRA levels may influence the patient's likelihood of identifying a compatible organ donor.
Baseline compared to 6 months post-AHSCT (at the time of re-listing).

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Rate of Successful Kidney Transplantation
Délai: Up to 12 months post-AHSCT
The proportion of highly sensitized patients who successfully receive an HLA-compatible deceased-donor kidney transplant after being reactivated on the waiting list following the immune reset.
Up to 12 months post-AHSCT

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Hospital Universitari Vall d'Hebron Research Institute

Collaborateurs

Hospital Clinic of Barcelona

Les enquêteurs

  • Chercheur principal: Oriol Bestard, Hospital Vall d'hebrón

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

1 février 2024

Achèvement primaire (Estimé)

1 mai 2027

Achèvement de l'étude (Estimé)

1 juin 2028

Dates d'inscription aux études

Première soumission

19 mai 2026

Première soumission répondant aux critères de contrôle qualité

19 mai 2026

Première publication (Réel)

26 mai 2026

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

4 juin 2026

Dernière mise à jour soumise répondant aux critères de contrôle qualité

2 juin 2026

Dernière vérification

1 mai 2026

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • 2023-506478-11-01 (Ctis)

Plan pour les données individuelles des participants (IPD)

Prévoyez-vous de partager les données individuelles des participants (DPI) ?

NON

Description du régime IPD

Individual participant data will not be shared to protect patient privacy and maintain confidentiality, in accordance with institutional data protection policies and the small sample size of this pilot study.

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Non

Étudie un produit d'appareil réglementé par la FDA américaine

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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