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

NCT06809075 | Recruiting DMC

• 2 other identifiers: RESET2023-506478-11-01
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Kidney Disease; Kidney Transplant; Kidney Transplant Candidates

Keywords

HLA; TPHa; Kidney transplant; hypersensitized patient; cPRA; immunosuppression; DSA; aHSCT

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (9)

• Total number of HLA antibodies eliminated

  from enrolment to 6 months post-aHSCT

• 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

  from enrolment to 6 months post-aHSCT

• Proportion of patients transplanted with a compatible donor

  from enrolment to 12 months post-aHSCT

• Adverse reactions related to aHSCT

  from enrolment to 12 months post-aHSCT

Study Arms (1)

hypersensitive patients undergoing aHSCT

EXPERIMENTAL

hypersensitive patients undergoing aHSCT. All patients in this study participate in this arm.

Procedure: hematopoietic precursor transplantation (TPHa)

Interventions

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.

hypersensitive patients undergoing aHSCT

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hospital Universitari Vall d'Hebron Research Institute: lead

Study Sites (1)

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

RECRUITING

MeSH Terms

Conditions

Kidney Diseases

Condition Hierarchy (Ancestors)

Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Central Study Contacts

Oriol Bestard, MD, PhD

CONTACT

932746000; oriol.betsard@vallhebron.cat

Delphine Kervella, MD, PhD

CONTACT

932746000; delphine.kervella@vallhebron.cat

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 3, 2024
• First Posted: February 5, 2025
• Study Start: April 5, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: February 12, 2025

Record last verified: 2025-02

Locations

ES (1)