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)

Overview

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.

Interventions

• 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.

Primary outcome measures

• To evaluate the impact of autologous hematopoietic stem cell transplantation (aHSCT) [Time frame: 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 [Time frame: from enrolment to 12 months post-aHSCT]

Secondary outcome measures (9)

• Total number of HLA antibodies eliminated [Time frame: from enrolment to 6 months post-aHSCT]
• Average number of HLA antibodies eliminated [Time frame: from enrolment to 6 months post-aHSCT]
• Mean reduction in MFI of immunodominant HLA antibody, class I and class II [Time frame: from enrolment to 6 months post-aHSCT]
• Proportion of patients transplanted with a compatible donor [Time frame: from enrolment to 12 months post-aHSCT]
• Adverse reactions related to aHSCT [Time frame: from enrolment to 12 months post-aHSCT]
• Incidence of opportunistic infections [Time frame: 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 [Time frame: 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 [Time frame: from kidney transplant to 1 year post kidney transplant]
• 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)]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Spain · 1 center

• Hospital Universitari Vall d'Hebron — Barcelona

Identifiers

NCT: NCT06809075 · RESET · 2023-506478-11-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗