Evaluation of Desensitization Protocols in HLA-incompatible Kidney-transplant Candidates

• Status: Terminated
• Trial end date: 2019-11-21
• Target enrollment: 0
• Participant gender: All

Summary

Kidney transplantation is the best renal-replacement in the setting of end-stage renal disease. However, some transplant candidates have developed anti-HLA alloantibodies (human leukocyte antigen). When they are numerous and when their strength assessed by mean fluorescence intensity (MFI) is high it is very complicated to find-out a suitable kidney allograft against which the recipient has a negative cross-match. In such a case the only hope for the patient is desensitization therapy, whereby the treatment will decrease anti-HLA alloantibodies below a threshold, i.e. MFI < 3,000, enabling kidney transplantation without risking antibody-mediated rejection. Desensitization relies on i) apheresis technics in order to withdraw circulating anti-HLA antibodies, and ii) immunosuppression, i.e. rituximab or tocilizumab, targeting B-lymphocytes, and tacrolimus/mycophenolic acid/steroids targeting T-cells. The type of apheresis is guided by the pre-desensitization MFI of anti-HLA alloantibodies, e.g. double filtration plasmapheresis or semispecific immunoadsorption. Likely the choice between rituximab and tocilizumab depends also on predesensitization anti-HLA antibody MFIs. At the end of the desensitization process, the patient will be able to get a kidney transplant either from a live-donor or from a deceased donor.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University Hospital, Grenoble
• Treatments: Rituximab

Criteria

Inclusion Criteria:

• Patients on the kidney transplant list, waiting for a first or repeat transplant

• Presence of anti HLA antibodies either class I and/or II

• Sensitized against a potential living donor or have been on the waiting list for at least 3 years and having no potential live-donor

• Patients eligible for desensitization will receive either rituximab alone, or rituximab plus apheresis, or tocilizumab before rituximab

• Normal recent (<6 months) cardiac workup

• Vaccinated against pneumococcus and meningococcus B and C

• Willingness of the patient to undergo the desensitization process and Express consent of the patient

• for women of childbearing age, effective contraception or abstinence

• Affiliated to a social security scheme or of such a scheme

Exclusion Criteria:

• Active underlying infections or neoplasia

• Pregnant women, parturient or breastfeeding

• Subject in exclusion period of another study

• Subject under administrative or judicial control

• Subject who cannot be contacted in an emergency

• Rituximab contra indication: hypersensitivity (to active substance or murine protein), active and severe infections, patients in a severely immunocompromised state, severe heart failure or severe, uncontrolled cardiac disease.

• Tocilizumab contra indication: hypersensitivity, active and severe infections. Apheresis contra indication: active and severe infection, untreated or instable coagulation disorders, unstable coronary disease, recent stroke, hemodynamic instability.