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

Not Applicable

Recruiting

• Conditions: Kidney Disease; Kidney Transplant; Kidney Transplant Candidates

• Registration Number: NCT06809075
• Lead Sponsor: Hospital Universitari Vall d'Hebron Research Institute

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2024-04-05
• Study First Submitted: 2024-10-03
• Status Verified: 2025-02
• Study First Submitted QC: 2025-02-04
• Study First Posted: 2025-02-05
• Last Update Submitted: 2025-02-10
• Last Update Posted: 2025-02-12
• Primary Completion: 2026-12-01
• Study Completion: 2026-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 10

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
To evaluate the impact of autologous hematopoietic stem cell transplantation (aHSCT)	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.
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	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 Outcome Measures

Name	Time	Method
Adverse reactions related to aHSCT	from enrolment to 12 months post-aHSCT	Mesure the number of adverse reactions related to aHSCT
Total number of HLA antibodies eliminated	from enrolment to 6 months post-aHSCT	Total number of HLA antibodies eliminated
Average number of HLA antibodies eliminated	from enrolment to 6 months post-aHSCT	Average number of HLA antibodies eliminated
Changes in the clonal and phenotypic repertoire of B and T cells.	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
Mean reduction in MFI of immunodominant HLA antibody, class I and class II	from enrolment to 6 months post-aHSCT	Mean reduction in MFI of immunodominant HLA antibody, class I and class II
Proportion of patients transplanted with a compatible donor	from enrolment to 12 months post-aHSCT	Proportion of patients transplanted with a compatible donor
Incidence of opportunistic infections	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
Incidence of clinical and/or subclinical rejection mediated by antibodies in the first year after kidney transplantation	from kidney trasplantation to 12 months after	Incidence of clinical and/or subclinical rejection mediated by antibodies in the first year after kidney transplantation
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	Proportion of patients free of DSA and/or donor-specific memory B cells at 1 year after kidney transplant

Trial Locations

Locations (1)

Hospital Universitari Vall d'Hebron; 🇪🇸 Barcelona, Spain