Immunological Reset to Enable Access to Hla-compatible Kidney Transplantation in Highly Sensitized Patients (RESET)
Immune Reset to Allow Access to Hla-compatible Kidney Transplantation in Hyperimmunized Patients
Hospital Universitari Vall d'Hebron Research Institute
10 participants
Feb 1, 2024
INTERVENTIONAL
Conditions
Summary
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.
Eligibility
Inclusion Criteria6
- 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.
- Adequate bone marrow, hepatic, cardiac, and pulmonary function to safely undergo the conditioning regimen and AHSCT.
- Capable of understanding the study requirements and providing written informed consent.
Exclusion Criteria7
- 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.
- Previous autologous or allogeneic hematopoietic stem cell transplantation.
- Pregnancy or breastfeeding.
- Any psychiatric, medical, or geographical condition that, in the investigator's opinion, prevents compliance with the protocol and long-term follow-up.
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Interventions
A 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.
Locations(1)
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NCT07607197