Immunological Reset to Enable Access to Hla-compatible Kidney Transplantation in Highly Sensitized Patients (RESET)

NCT07607197 | Recruiting Phase 1 DMC

• 1 other identifier: 2023-506478-11-01
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Kidney Failure, Chronic; Kidney Transplantation; Alloimmunization; HLA Sensitization; End Stage Cronic Kidney Disease; Highly Sensitized Patients Awaiting Kidney Transplant

Keywords

Autologous Hematopoietic Stem Cell Transplantation; AHSCT; Kidney Transplantation; Highly sensitized; Hyperimmunized; Desensitization; Anti-HLA Antibodies; CD34+ Cells; Transplant Immunology; End-Stage Kidney Disease; Immune Reset

Outcome Measures

Primary Outcomes (2)

• 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.

  Baseline compared to 6 months post-AHSCT (at the time of re-listing).

• 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).

  From baseline up to 12 months post-AHSCT.

Secondary Outcomes (1)

• Rate of Successful Kidney Transplantation

  Up to 12 months post-AHSCT

Study Arms (1)

Autologous Hematopoietic Stem Cell Transplantation (AHSCT)

EXPERIMENTAL

Participants undergo a non-myeloablative conditioning regimen for intense lymphodepletion consisting of intravenous Rituximab, Cyclophosphamide (adjusted for end-stage renal disease), and Thymoglobulin (rATG). This is followed by peripheral blood stem cell collection via leukapheresis, CD34+ immunomagnetic selection, and the reinfusion of purified autologous CD34+ progenitors (target dose \>= 3 x 10⁶ cells/kg). At 6 months post-AHSCT, patients are reactivated on the deceased-donor kidney transplant waiting list.

Biological: Autologous Hematopoietic Stem Cell Transplantation

Interventions

Autologous Hematopoietic Stem Cell Transplantation BIOLOGICAL

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.

Also known as: AHSCT, Autologous CD34+ stem cell infusion

Autologous Hematopoietic Stem Cell Transplantation (AHSCT)

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hospital Universitari Vall d'Hebron Research Institute: lead
• Hospital Clinic of Barcelona: collaborator

Study Sites (1)

Hospital Universitari Vall d'Hebron

Barcelona, Catalonia, 08035, Spain

RECRUITING

MeSH Terms

Conditions

Kidney Failure, Chronic

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Oriol Bestard

  Hospital Vall d'Hebron

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Oriol Bestard, Nephrologist

CONTACT

34932607400; oriol.bestard@vallhebron.cat

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a single-arm, open-label pilot study with a two-stage sequential design focused on safety monitoring. The trial initially enrolls a cohort of 4 patients in Phase 1 to evaluate safety over 12 months. Upon confirming an optimal safety profile, the trial proceeds to Phase 2 to enroll the remaining 6 patients. All 10 participants undergo the identical conditioning regimen and autologous hematopoietic stem cell transplantation protocol.

Study Record Dates

• First Submitted: May 19, 2026
• First Posted: May 26, 2026
• Study Start: February 1, 2024
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): June 1, 2028
• Last Updated: June 4, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)