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

Grenoble Alpes University Hospital Center (CHU)

Status: Terminated

Conditions: Kidney Transplantation; Hla-incompatible Kidney Transplant Candidates; End-stage Renal Disease

Treatments: Drug: Rituximab 375 mg/m2 at Day-15 (only for donors living); Drug: Rituximab 375 mg/m2 at Day-30; Other: Transplant Day-0; Drug: visits of tocilizumab injection (every 4 weeks, up to 5 visits)

Study type: Interventional

Funder types: Other

Identifiers

NCT03507348

38RC17.247

Details and patient eligibility

About

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.

Enrollment: 8 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Other

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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8 participants in 2 patient groups

Desensitization with Tocilizumab and rituximab (MFI >15000)

Other group

Treatment:

Other: Transplant Day-0

Drug: Rituximab 375 mg/m2 at Day-15 (only for donors living)

Drug: visits of tocilizumab injection (every 4 weeks, up to 5 visits)

Drug: Rituximab 375 mg/m2 at Day-30

Desensitization with Rituximab only (MFI<15000)

Other group

Treatment:

Other: Transplant Day-0

Drug: Rituximab 375 mg/m2 at Day-15 (only for donors living)

Drug: Rituximab 375 mg/m2 at Day-30