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

2 juni 2026 bijgewerkt door: 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.

Studie Overzicht

Toestand

Werving

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

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.

Studietype

Ingrijpend

Inschrijving (Geschat)

10

Fase

  • Fase 2
  • Fase 1

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studiecontact

Studie Locaties

  • Spanje
    • Catalonia
      • Barcelona, Catalonia, Spanje, 08035
        • Werving
        • Hospital Universitari Vall d'Hebron
        • Contact:
        • Hoofdonderzoeker:
          • Oriol Bestard, Nephrologist

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

  • Volwassen

Accepteert gezonde vrijwilligers

Nee

Beschrijving

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.

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: NVT
  • Interventioneel model: Opdracht voor een enkele groep
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: 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.
Biologisch: 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.
Andere namen:
  • AHSCT
  • Autologous CD34+ stem cell infusion

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Incidence of Treatment-Emergent Adverse Events (Safety Profile)
Tijdsspanne: 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
Tijdsspanne: 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).

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Rate of Successful Kidney Transplantation
Tijdsspanne: 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

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Hospital Universitari Vall d'Hebron Research Institute

Medewerkers

Hospital Clinic of Barcelona

Onderzoekers

  • Hoofdonderzoeker: Oriol Bestard, Hospital Vall d'hebrón

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Werkelijk)

1 februari 2024

Primaire voltooiing (Geschat)

1 mei 2027

Studie voltooiing (Geschat)

1 juni 2028

Studieregistratiedata

Eerst ingediend

19 mei 2026

Eerst ingediend dat voldeed aan de QC-criteria

19 mei 2026

Eerst geplaatst (Werkelijk)

26 mei 2026

Updates van studierecords

Laatste update geplaatst (Werkelijk)

4 juni 2026

Laatste update ingediend die voldeed aan QC-criteria

2 juni 2026

Laatst geverifieerd

1 mei 2026

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • 2023-506478-11-01 (Ctis)

Plan Individuele Deelnemersgegevens (IPD)

Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?

NEE

Beschrijving IPD-plan

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.

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Nee

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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