Kidney Failure, ChronicPhase 1/2HIPER-RESETNCT07607197
Immunological Reset to Enable Access to Hla-compatible Kidney Transplantation in Highly Sensitized Patients (RESET)
A Phase 1/2 study testing Autologous Hematopoietic Stem Cell Transplantation in people with Kidney Failure, Chronic and Kidney Transplantation, run by Hospital Universitari Vall d'Hebron Research Institute at 1 site in Spain.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Kidney Failure, Chronic, Kidney Transplantation, Alloimmunization
- What is being tested?
- Autologous Hematopoietic Stem Cell Transplantation
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteSpain
- Study dates
- 1 Feb 2024to Jun 2028
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Spain1 site, 1 recruiting
- Recruiting
Hospital Universitari Vall d'Hebron
Barcelona, Catalonia, 08035
Oriol Bestard, Nephrologist, 34932607400 ext. 4661, oriol.bestard@vallhebron.cat
Oriol Bestard, Nephrologist
About this study
Official title: Immune Reset to Allow Access to Hla-compatible Kidney Transplantation in Hyperimmunized Patients
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.
Read more
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.
Read the detailed description
This single-center, open-label, non-randomized phase Ib/II pilot study will evaluate the safety, feasibility, and immunological effects of autologous hematopoietic stem cell transplantation (AHSCT) in highly sensitized patients awaiting kidney transplantation.
A total of 10 hyperimmunized patients on the kidney transplant waiting list will be enrolled in two sequential phases. In Phase 1, four participants will undergo AHSCT with close safety monitoring during a 12-month follow-up period. In the absence of severe adverse events, participants will be reactivated on the deceased-donor kidney transplant waiting list at 6 months post-AHSCT. Following safety evaluation of the initial cohort, an additional six participants will be enrolled in Phase 2 to further assess the efficacy and safety of the strategy.
The intervention includes a non-myeloablative lymphodepletion and stem cell mobilization regimen followed by collection, CD34+ selection, and reinfusion of autologous hematopoietic progenitor cells. After AHSCT, eligible participants may undergo deceased-donor kidney transplantation following confirmation of HLA compatibility by standard crossmatch techniques.
Kidney transplant recipients will receive standard-of-care induction and maintenance immunosuppressive therapy according to institutional clinical practice.
The study also includes longitudinal immunological monitoring to characterize adaptive immune reconstitution and anti-HLA responses after AHSCT and kidney transplantation. Peripheral blood and bone marrow samples will be collected at predefined time points to evaluate T- and B-cell memory compartments, donor-specific antibodies, and pathogen-specific immune responses.
Primary objectives include assessment of safety and feasibility, as well as evaluation of changes in sensitization status and access to HLA-compatible kidney transplantation following AHSCT.
- Conditions
- Kidney Failure, Chronic, Kidney Transplantation, Alloimmunization, HLA Sensitization, End Stage Cronic Kidney Disease, Highly Sensitized Patients Awaiting Kidney Transplant
- Being tested
- Autologous Hematopoietic Stem Cell Transplantation
- 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
- Medical subject headings
- Kidney Failure, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Autologous Hematopoietic Stem Cell TransplantationBiological
Also called AHSCT, Autologous CD34+ stem cell infusion
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Biological: Autologous Hematopoietic Stem Cell Transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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).
Measured: From baseline up to 12 months post-AHSCT.
Secondary outcomes (1)
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.
Measured: Up to 12 months post-AHSCT
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 May 2026
- Study start1 Feb 2024
- Primary completionMay 2027 (estimated)
- Study completionJun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Kidney Failure, ChronicStudies of the same condition, open and under way.
- More trials run by Hospital Universitari Vall d'Hebron Research InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Hospital Clinic of Barcelona
- Responsible party
- Sponsor
- Investigators
- Oriol Bestard, Principal investigator, Hospital Vall d'Hebron
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07607197
- Sponsor's protocol ID
- 2023-506478-11-01
- Other IDs
- 2023-506478-11-01, 2023
- Acronym
- HIPER-RESET
- Status last verified
- May 2026
- First submitted
- 19 May 2026
- Last updated
- 4 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data will not be shared to protect patient privacy and maintain confidentiality, in accordance with institutional data protection policies and the small sample size of this pilot study.
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immune Reset to Allow Access to Hla-compatible Kidney Transplantation in Hyperimmunized Patients
- ClinicalTrials.gov ID
- NCT07607197
- Acronym / sponsor ID
- HIPER-RESET / 2023-506478-11-01
- 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
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Hospital Universitari Vall d'Hebron Research InstituteUniversity, hospital or other
- Collaborators
- Hospital Clinic of Barcelona
- Study start
- 1 Feb 2024 (actual)
- Primary completion
- May 2027 (estimated)
- Study completion
- Jun 2028 (estimated)
- First posted
- 26 May 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This single-center, open-label, non-randomized phase Ib/II pilot study will evaluate the safety, feasibility, and immunological effects of autologous hematopoietic stem cell transplantation (AHSCT) in highly sensitized patients awaiting kidney transplantation.
A total of 10 hyperimmunized patients on the kidney transplant waiting list will be enrolled in two sequential phases. In Phase 1, four participants will undergo AHSCT with close safety monitoring during a 12-month follow-up period. In the absence of severe adverse events, participants will be reactivated on the deceased-donor kidney transplant waiting list at 6 months post-AHSCT. Following safety evaluation of the initial cohort, an additional six participants will be enrolled in Phase 2 to further assess the efficacy and safety of the strategy.
The intervention includes a non-myeloablative lymphodepletion and stem cell mobilization regimen followed by collection, CD34+ selection, and reinfusion of autologous hematopoietic progenitor cells. After AHSCT, eligible participants may undergo deceased-donor kidney transplantation following confirmation of HLA compatibility by standard crossmatch techniques.
Kidney transplant recipients will receive standard-of-care induction and maintenance immunosuppressive therapy according to institutional clinical practice.
The study also includes longitudinal immunological monitoring to characterize adaptive immune reconstitution and anti-HLA responses after AHSCT and kidney transplantation. Peripheral blood and bone marrow samples will be collected at predefined time points to evaluate T- and B-cell memory compartments, donor-specific antibodies, and pathogen-specific immune responses.
Primary objectives include assessment of safety and feasibility, as well as evaluation of changes in sensitization status and access to HLA-compatible kidney transplantation following AHSCT.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Autologous Hematopoietic Stem Cell Transplantation (AHSCT) | Experimental | Biological: Autologous Hematopoietic Stem Cell TransplantationParticipants 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. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Autologous Hematopoietic Stem Cell TransplantationAlso: AHSCT, Autologous CD34+ stem cell infusionA 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. | Biological | Autologous Hematopoietic Stem Cell Transplantation (AHSCT) |
Primary outcome
Change in Calculated Panel Reactive Antibody (cPRA) Levels
Time frame: Baseline compared to 6 months post-AHSCT (at the time of re-listing).
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)
Time frame: From baseline up to 12 months post-AHSCT.
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).
1 secondary outcome
Rate of Successful Kidney Transplantation
Time frame: Up to 12 months post-AHSCT
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2026.
- Individual participant dataSharing planned: No. Individual participant data will not be shared to protect patient privacy and maintain confidentiality, in accordance with institutional data protection policies and the small sample size of this pilot study.
Related trials for Kidney Failure, Chronic
Active, not recruitingPhase 2
Safety and Efficacy of Empagliflozin in Hemodialysis
End Stage Renal Disease
RecruitingPhase 3
Study to Assess the Efficacy, Pharmacokinetics, Safety and Tolerability of Atrasentan in Pediatric Patients With Primary IgAN
Berger Disease, Bergers Disease
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)
Not yet recruiting
Hypothermic Kidney Machine Perfusion With Omnisol
End Stage Renal Disease (ESRD), Kidney Transplant
Not yet recruiting
An Individuation Intervention to Reduce Socioeconomic Disparities in Chronic Kidney Disease Care
Chronic Kidney Diseases
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Oriol Bestard principal investigator
Hospital Vall d'Hebron
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Autologous Hematopoietic Stem Cell Transplantation in people with Kidney Failure, Chronic and Kidney Transplantation, run by Hospital Universitari Vall d'Hebron Research Institute at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 4 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Oriol Bestard, Nephrologist (34932607400 ext. 4661, oriol.bestard@vallhebron.cat), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Calculated Panel Reactive Antibody (cPRA) Levels (time frame: Baseline compared to 6 months post-AHSCT (at the time of re-listing).). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2026.