The purpose of this clinical trial is to evaluate whether a temporary reprogramming of the immune system can help highly sensitized (hyperimmunized) patients with end-stage kidney disease safely receive a compatible kidney transplant.
Patients who are highly sensitized have developed an extremely high level of antibodies against human leukocyte antigens (HLA), often due to previous transplants, pregnancies, or blood transfusions. This condition makes it nearly impossible for them to find a compatible organ donor, leaving them stuck on dialysis indefinitely.
This study tests an innovative strategy using Autologous Hematopoietic Stem Cell Transplantation (AHSCT). The procedure involves an intensive conditioning regimen using a combination of medications (cyclophosphamide, thymoglobulin, and rituximab) to deeply clear out the patient's existing mature immune cells. This is followed by the reinfusion of the patient's own previously collected and purified blood stem cells (CD34+ cells) to rebuild the immune system from scratch.
The investigators hypothesize that this procedure will eliminate the "immunological memory" cells responsible for producing the problematic anti-HLA antibodies, resetting the immune system to a "naive" or inactive state. This immune reset is expected to eliminate or significantly lower circulating HLA antibodies, creating a critical window of opportunity for these patients to successfully receive a compatible kidney transplant from the deceased-donor waiting list.
Patients aged between 18 and 60 years.
Diagnosis of end-stage kidney disease (ESRD) currently maintained on chronic dialysis.
Highly sensitized/hyperimmunized status, defined by a high calculated Panel Reactive Antibody (cPRA) level (e.g., >= 95%).
Active status on the deceased-donor kidney transplant waiting list.
Contraindications to the conditioning regimen medications (rituximab, cyclophosphamide, or rATG).
Active, uncontrolled systemic infection, or chronic active infection (including HIV, active Hepatitis B or C, or active tuberculosis).
Significant cardiac dysfunction (e.g., Left Ventricular Ejection Fraction < 50%) or severe underlying pulmonary disease.
History of malignant neoplasm within the past 5 years, excluding successfully treated non-melanoma skin cancer or carcinoma in situ.
Single group
Autologous Hematopoietic Stem Cell Transplantation
Biological/VaccineA comprehensive cell therapy protocol involving intense non-myeloablative lymphodepletion followed by stem cell rescue. The intervention includes sequential intravenous administration of Rituximab, Cyclophosphamide (specifically dose-adjusted for end-stage renal disease), and rabbit Thymoglobulin (rATG). Following conditioning, participants receive an intravenous reinfusion of purified autologous CD34+ hematopoietic progenitor cells collected via peripheral blood leukapheresis at a target dose of \>= 3 x 10⁶ cells/kg, with a cryopreserved backup aliquot maintained for safety.
Change in Calculated Panel Reactive Antibody (cPRA) Levels
Assessment of changes in circulating anti-HLA antibodies following the AHSCT protocol, measured by calculated Panel Reactive Antibody (cPRA) levels compared to baseline. Changes in cPRA levels may influence the patient's likelihood of identifying a compatible organ donor.
Incidence of Treatment-Emergent Adverse Events (Safety Profile)
Evaluation of the safety and tolerability of the intense conditioning regimen and autologous hematopoietic stem cell transplantation (AHSCT). This includes monitoring the number, severity, and type of serious and non-serious adverse events, evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE).
Rate of Successful Kidney Transplantation
The proportion of highly sensitized patients who successfully receive an HLA-compatible deceased-donor kidney transplant after being reactivated on the waiting list following the immune reset.
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Hospital Universitari Vall d'Hebron Research Institute
Lead sponsor
Hospital Clinic of Barcelona
Collaborator
