Kidney Disease, Kidney Transplant, Kidney Transplant Candidates
Conditions
Keywords
HLA, TPHa, Kidney transplant, hypersensitized patient, cPRA, immunosuppression, DSA, aHSCT
Brief summary
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
PROCEDUREhematopoietic 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.
Sponsors
Hospital Universitari Vall d'Hebron Research Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. The patient must be able to understand and give written consent. 2. Women and men between 18 and 65 years old. 3. Patients with chronic kidney disease who are on renal therapy replacement with dialysis. 4. 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. 5. cPRA calculated of more than 97% and having been in the program of prioritization for more than 3 years 6. Positive IgG serologies for Cytomegalovirus and Epstein Barr. 7. 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.). 8. Patients vaccinated against tetanus, influenza, pneumococcus and herpes zoster
Exclusion criteria
1. Current known infection, recurrent bacteria, virus, fungus or fungus bacteria, or other infections (such as HIV, hepatitis B, hepatitis C, or zoster). 2. Concomitant serious uncontrolled major organ disease. 3. 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. 4. Patients with primary or secondary immunodeficiencies. 5. Patient with an active history of tuberculosis (even if treated) or patients with untreated latent tuberculosis. 6. Malignancy during the 5 years prior to screening, except for carcinoma of the basal cell or squamous cell carcinoma properly removed. 7. Known abuse of alcohol, drugs or chemicals within 1 year prior to screening. 8. Patients with complicated peripheral venous access 9. Neutropenia (ANC \<1000/uL) or thrombocytopenia (platelet count \<100,000/uL) during the 4 weeks prior to screening. 10. Severe allergic or anaphylactic reactions to human monoclonal antibodies, humanized or murine. 11. Treatment with any investigational agent during the 4 weeks (or 5 half-lives of the investigational drug, whichever is longer) prior to screening. 12. Immunization with live vaccine during the 2 months prior to screening. 13. Pregnant or breastfeeding women.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate the impact of autologous hematopoietic stem cell transplantation (aHSCT) | from enrolment to 12 months post-TPHa | Variable composed with the proportion of patients in whom ≥10 HLA, class I or class II antibodies are eliminated (undetectable or \<1000 MFI) or the percentage of baseline cPRA is decreased at 6 months after aHSCT, in the absence of severe undesirable effects related to the treatment. |
| 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 | from enrolment to 12 months post-aHSCT | 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 * Elimination/reduction of HLA antibody-secreting plasma cells in the bone marrow * Absence/reduction of HLA-specific memory B cells in circulation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients transplanted with a compatible donor | from enrolment to 12 months post-aHSCT | Proportion of patients transplanted with a compatible donor |
| Total number of HLA antibodies eliminated | from enrolment to 6 months post-aHSCT | Total number of HLA antibodies eliminated |
| Adverse reactions related to aHSCT | from enrolment to 12 months post-aHSCT | Mesure the number of adverse reactions related to aHSCT |
| Average number of HLA antibodies eliminated | from enrolment to 6 months post-aHSCT | Average number of HLA antibodies eliminated |
| Incidence of clinical and/or subclinical rejection mediated by antibodies in the first year after kidney transplantation | from kidney trasplantation to 12 months after | Incidence of clinical and/or subclinical rejection mediated by antibodies in the first year after kidney transplantation |
| Proportion of patients free of DSA and/or donor-specific memory B cells at 1 year after kidney transplant | from kidney transplant to 1 year post kidney transplant | Proportion of patients free of DSA and/or donor-specific memory B cells at 1 year after kidney transplant |
| Changes in the clonal and phenotypic repertoire of B and T cells. | From aHSCT to 12 months after aHSCT or 12 months after kidney transplant (if it's occurs) | Changes in the clonal and phenotypic repertoire of B and T cells mesure with cytometry |
| Incidence of opportunistic infections | From aHSCT to 12 months after aHSCT or 12 months after kidney transplant (if it's occurs) | Mesure the Incidence of opportunistic infections in treated patients |
| Mean reduction in MFI of immunodominant HLA antibody, class I and class II | from enrolment to 6 months post-aHSCT | Mean reduction in MFI of immunodominant HLA antibody, class I and class II |
Countries
Spain
Contacts
Primary ContactOriol Bestard, MD, PhD
Backup ContactDelphine Kervella, MD, PhD
Outcome results
None listed