Clinical trial NCT06809075: Immunological Reset to Allow Access to HLA Compatible Transplantation in Highly Sensitized Kidney Transplant Candidates Through Non-myeloablative Autologous Stemm Cell Transplantation
Official 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Kidney Disease
Kidney Transplant
Kidney Transplant Candidates
Keywords: HLA
TPHa
Kidney transplant
hypersensitized patient
cPRA
immunosuppression
DSA
aHSCT
Lead sponsor: Hospital Universitari Vall d'Hebron Research Institute
Sponsor class: OTHER
First posted: 2025-02-05
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: To evaluate the impact of autologous hematopoietic stem cell transplantation (aHSCT)
timeFrame: from enrolment to 12 months post-TPHa
measure: 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
timeFrame: from enrolment to 12 months post-aHSCT
Secondary outcomes:
measure: Total number of HLA antibodies eliminated
timeFrame: from enrolment to 6 months post-aHSCT
measure: Average number of HLA antibodies eliminated
timeFrame: from enrolment to 6 months post-aHSCT
measure: Mean reduction in MFI of immunodominant HLA antibody, class I and class II
timeFrame: from enrolment to 6 months post-aHSCT
measure: Proportion of patients transplanted with a compatible donor
timeFrame: from enrolment to 12 months post-aHSCT
measure: Adverse reactions related to aHSCT
timeFrame: from enrolment to 12 months post-aHSCT
measure: Incidence of opportunistic infections
timeFrame: From aHSCT to 12 months after aHSCT or 12 months after kidney transplant (if it's occurs)
measure: Incidence of clinical and/or subclinical rejection mediated by antibodies in the first year after kidney transplantation
timeFrame: from kidney trasplantation to 12 months after
measure: Proportion of patients free of DSA and/or donor-specific memory B cells at 1 year after kidney transplant
timeFrame: from kidney transplant to 1 year post kidney transplant
measure: Changes in the clonal and phenotypic repertoire of B and T cells.
timeFrame: From aHSCT to 12 months after aHSCT or 12 months after kidney transplant (if it's occurs)
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
Study officials:
References: