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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Kidney Disease; Kidney Transplant; Kidney Transplant Candidates
• Intervention / Treatment: Procedure: hematopoietic precursor transplantation (TPHa)

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Oriol Bestard, MD, PhD; Phone Number: 4661 932746000; Email: oriol.betsard@vallhebron.cat
• Study Contact Backup: Name: Delphine Kervella, MD, PhD; Phone Number: 4661 932746000; Email: delphine.kervella@vallhebron.cat

Study Locations

• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Universitari Vall d'Hebron
    • Contact: Oriol Bestard, MD, PhD; Phone Number: 932746000; Email: oriol.bestard@vallhebron.cat

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. The patient must be able to understand and give written consent.
2. Women and men between 18 and 65 years old.
3. Patients with chronic kidney disease who are on renal therapy replacement with dialysis.
4. 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.
5. cPRA calculated of more than 97% and having been in the program of prioritization for more than 3 years
6. Positive IgG serologies for Cytomegalovirus and Epstein Barr.
7. 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.).
8. Patients vaccinated against tetanus, influenza, pneumococcus and herpes zoster

Exclusion Criteria:

1. Current known infection, recurrent bacteria, virus, fungus or fungus bacteria, or other infections (such as HIV, hepatitis B, hepatitis C, or zoster).
2. Concomitant serious uncontrolled major organ disease.
3. 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.
4. Patients with primary or secondary immunodeficiencies.
5. Patient with an active history of tuberculosis (even if treated) or patients with untreated latent tuberculosis.
6. Malignancy during the 5 years prior to screening, except for carcinoma of the basal cell or squamous cell carcinoma properly removed.
7. Known abuse of alcohol, drugs or chemicals within 1 year prior to screening.
8. Patients with complicated peripheral venous access
9. Neutropenia (ANC <1000/uL) or thrombocytopenia (platelet count <100,000/uL) during the 4 weeks prior to screening.
10. Severe allergic or anaphylactic reactions to human monoclonal antibodies, humanized or murine.
11. Treatment with any investigational agent during the 4 weeks (or 5 half-lives of the investigational drug, whichever is longer) prior to screening.
12. Immunization with live vaccine during the 2 months prior to screening.
13. Pregnant or breastfeeding women.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: hypersensitive patients undergoing aHSCT; hypersensitive patients undergoing aHSCT. All patients in this study participate in this arm.	Procedure: hematopoietic precursor transplantation (TPHa); 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the impact of autologous hematopoietic stem cell transplantation (aHSCT)	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.	from enrolment to 12 months post-TPHa
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	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	from enrolment to 12 months post-aHSCT

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total number of HLA antibodies eliminated	Total number of HLA antibodies eliminated	from enrolment to 6 months post-aHSCT
Average number of HLA antibodies eliminated	Average number of HLA antibodies eliminated	from enrolment to 6 months post-aHSCT
Mean reduction in MFI of immunodominant HLA antibody, class I and class II	Mean reduction in MFI of immunodominant HLA antibody, class I and class II	from enrolment to 6 months post-aHSCT
Proportion of patients transplanted with a compatible donor	Proportion of patients transplanted with a compatible donor	from enrolment to 12 months post-aHSCT
Adverse reactions related to aHSCT	Mesure the number of adverse reactions related to aHSCT	from enrolment to 12 months post-aHSCT
Incidence of opportunistic infections	Mesure the Incidence of opportunistic infections in treated patients	From aHSCT to 12 months after aHSCT or 12 months after kidney transplant (if it's occurs)
Incidence of clinical and/or subclinical rejection mediated by antibodies in the first year after kidney transplantation	Incidence of clinical and/or subclinical rejection mediated by antibodies in the first year after kidney transplantation	from kidney trasplantation to 12 months after
Proportion of patients free of DSA and/or donor-specific memory B cells at 1 year after kidney transplant	Proportion of patients free of DSA and/or donor-specific memory B cells at 1 year after kidney transplant	from kidney transplant to 1 year post kidney transplant
Changes in the clonal and phenotypic repertoire of B and T cells.	Changes in the clonal and phenotypic repertoire of B and T cells mesure with cytometry	From aHSCT to 12 months after aHSCT or 12 months after kidney transplant (if it's occurs)

Collaborators and Investigators

• Sponsor: Hospital Universitari Vall d'Hebron Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): April 5, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: October 3, 2024
• First Submitted That Met QC Criteria: February 4, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 10, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: immunosuppression; Kidney transplant; HLA; DSA; aHSCT; cPRA; TPHa; hypersensitized patient
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Kidney Diseases
• Other Study ID Numbers: RESET (Alias Study Number); 2023-506478-11-01 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No