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NCT Number: NCT06809075

Immunological Reset to Allow Access to HLA Compatible Transplantation in Highly Sensitized Kidney Transplant Candidates Through Non-myeloablative Autologous Stemm Cell Transplantation

This is a study for hypersensitized patients who have been waiting for more than 3 years for an offer for a kidney transplant. The objective is to perform a transplant of autologous hematopoietic precursors with the aim of producing what we call an immunological reset to make the maximum number of anti-HLA antibodies disappear and thus increase the chances of the patient receiving an offer for a kidney transplant.

Recruiting

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Key information

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location status: Recruiting

Location contact

Oriol Bestard, MD, PhD

CONTACT

[email protected]

932746000

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • The patient must be able to understand and give written consent.
  • Women and men between 18 and 65 years old.
  • Patients with chronic kidney disease who are on renal therapy replacement with dialysis.
  • Patient who is on the waiting list for kidney transplant from a death donor and who has not received an offer for a compatible transplant in the last 3 years within the national PATHI prioritization program.
  • cPRA calculated of more than 97% and having been in the program of prioritization for more than 3 years
  • Positive IgG serologies for Cytomegalovirus and Epstein Barr.
  • Women of childbearing potential must have a negative pregnancy test upon entry to the study and must agree to use safe contraceptive methods according to the guideline CTFG recommendations on contraception in clinical trials during duration of the study (condoms are considered safe methods male and female, oral contraceptives, etc.).
  • Patients vaccinated against tetanus, influenza, pneumococcus and herpes zoster

Exclusion criteria

  • Current known infection, recurrent bacteria, virus, fungus or fungus bacteria, or other infections (such as HIV, hepatitis B, hepatitis C, or zoster).
  • Concomitant serious uncontrolled major organ disease.
  • Any infection that requires hospitalization and intravenous treatment with antibiotics during the 4 weeks prior to screening, or oral treatment with antibiotics the previous 2 weeks.
  • Patients with primary or secondary immunodeficiencies.
  • Patient with an active history of tuberculosis (even if treated) or patients with untreated latent tuberculosis.
  • Malignancy during the 5 years prior to screening, except for carcinoma of the basal cell or squamous cell carcinoma properly removed.
  • Known abuse of alcohol, drugs or chemicals within 1 year prior to screening.
  • Patients with complicated peripheral venous access
  • Neutropenia (ANC <1000/uL) or thrombocytopenia (platelet count <100,000/uL) during the 4 weeks prior to screening.
  • Severe allergic or anaphylactic reactions to human monoclonal antibodies, humanized or murine.
  • Treatment with any investigational agent during the 4 weeks (or 5 half-lives of the investigational drug, whichever is longer) prior to screening.
  • Immunization with live vaccine during the 2 months prior to screening.
  • Pregnant or breastfeeding women.

Treatment and study plan

hematopoietic precursor transplantation (TPHa)

Procedure

An apheresis is performed on the patients and a selection of CD34 hematopoietic progenitors is performed. Subsequently, conditioning is performed with cyclophosphamide, thymoglobulin, corticosteroids and rituximab to subsequently infuse the hematopoietic precursors.

Primary outcomes

  1. To evaluate the impact of autologous hematopoietic stem cell transplantation (aHSCT)

    Time frame: from enrolment to 12 months post-TPHa

    Variable composed with the proportion of patients in whom ≥10 HLA, class I or class II antibodies are eliminated (undetectable or <1000 MFI) or the percentage of baseline cPRA is decreased at 6 months after aHSCT, in the absence of severe undesirable effects related to the treatment.

  2. Proportion of patients achieving all of the following items at 6 months post-aHSCT or at the time of kidney transplant, if a compatible offer is received

    Time frame: from enrolment to 12 months post-aHSCT

    Proportion of patients achieving all of the following items at 6 months post-aHSCT or at the time of kidney transplant, if a compatible offer is received

    • Elimination/reduction of HLA antibody-secreting plasma cells in the bone marrow
    • Absence/reduction of HLA-specific memory B cells in circulation

Secondary outcomes

  1. Total number of HLA antibodies eliminated

    Time frame: from enrolment to 6 months post-aHSCT

    Total number of HLA antibodies eliminated

  2. Average number of HLA antibodies eliminated

    Time frame: from enrolment to 6 months post-aHSCT

    Average number of HLA antibodies eliminated

  3. Mean reduction in MFI of immunodominant HLA antibody, class I and class II

    Time frame: from enrolment to 6 months post-aHSCT

    Mean reduction in MFI of immunodominant HLA antibody, class I and class II

  4. Proportion of patients transplanted with a compatible donor

    Time frame: from enrolment to 12 months post-aHSCT

    Proportion of patients transplanted with a compatible donor

  5. Adverse reactions related to aHSCT

    Time frame: from enrolment to 12 months post-aHSCT

    Mesure the number of adverse reactions related to aHSCT

  6. Incidence of opportunistic infections

    Time frame: From aHSCT to 12 months after aHSCT or 12 months after kidney transplant (if it's occurs)

    Mesure the Incidence of opportunistic infections in treated patients

  7. Incidence of clinical and/or subclinical rejection mediated by antibodies in the first year after kidney transplantation

    Time frame: from kidney trasplantation to 12 months after

    Incidence of clinical and/or subclinical rejection mediated by antibodies in the first year after kidney transplantation

  8. Proportion of patients free of DSA and/or donor-specific memory B cells at 1 year after kidney transplant

    Time frame: from kidney transplant to 1 year post kidney transplant

    Proportion of patients free of DSA and/or donor-specific memory B cells at 1 year after kidney transplant

  9. Changes in the clonal and phenotypic repertoire of B and T cells.

    Time frame: From aHSCT to 12 months after aHSCT or 12 months after kidney transplant (if it's occurs)

    Changes in the clonal and phenotypic repertoire of B and T cells mesure with cytometry

Study contacts

Contact information is provided by the study sponsor or research team.

Delphine Kervella, MD, PhD

CONTACT

[email protected]

932746000 ext. 4661

Oriol Bestard, MD, PhD

CONTACT

[email protected]

932746000 ext. 4661

Sponsors and collaborators

Lead sponsor

Hospital Universitari Vall d'Hebron Research Institute

Other

Registry information

Official study title

Immunological Reset to Allow Access to HLA Compatible Transplantation in Highly Sensitized Kidney Transplant Candidates Through Non-myeloablative Autologous Stemm Cell Transplantation (RESET TRIAL)

Acronym: RESET

Important dates

Study start
2024
Primary completion
2026
Study completion
2026
First posted
Feb 5, 2025
Registry last updated
Feb 12, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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