Clinical trial NCT03507348: Evaluation of Desensitization Protocols in HLA-incompatible Kidney-transplant Candidates
Official title: Evaluation of Desensitization Protocols in HLA-incompatible Kidney-transplant Candidates
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: End-stage Renal Disease
Kidney Transplantation
Hla-incompatible Kidney Transplant Candidates
Keywords: Anti-HLA alloantibodies
Desensitization therapy
Tocilizumab
Rituximab
Lead sponsor: University Hospital, Grenoble
Sponsor class: OTHER
First posted: 2018-04-25
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief 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.


Eligibility 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.

Primary outcomes:
measure: Description of the results of the strategy of desensitization in patients who will access to kidney transplantation from deceased or living donors.
timeFrame: at day 1 start of desensitization, at day 0 of Graft
Secondary outcomes:
measure: Desensitization efficacy with regards to DSA decrease and kidney transplantation
timeFrame: Day-198, at day-30 Graft, at day-15, at day0 of Graft,
measure: impairment of DSA synthesis
timeFrame: Day-198, at day-30 Graft, at day-15, at day0 of Graft,
measure: Impairment of immune response
timeFrame: Day-198, at day-30 Graft, at day-15, at day0 of Graft,
measure: Incidence of treatment desensitization protocols, emergent adverse events (safety and Tolerability)
timeFrame: Day-198, at day-30 Graft, at day-15
Other outcomes:
Locations:
city: La Tronche
country: France
facility: Grenoble Alpes University Hospital
Study officials:
References:
citation: Orandi BJ, Montgomery RA, Segev DL. Kidney Transplants from HLA-Incompatible Live Donors and Survival. N Engl J Med. 2016 Jul 21;375(3):288-9. doi: 10.1056/NEJMc1604523. No abstract available.
citation: Montgomery RA, Lonze BE, King KE, Kraus ES, Kucirka LM, Locke JE, Warren DS, Simpkins CE, Dagher NN, Singer AL, Zachary AA, Segev DL. Desensitization in HLA-incompatible kidney recipients and survival. N Engl J Med. 2011 Jul 28;365(4):318-26. doi: 10.1056/NEJMoa1012376.
citation: Vo AA, Choi J, Cisneros K, Reinsmoen N, Haas M, Ge S, Toyoda M, Kahwaji J, Peng A, Villicana R, Jordan SC. Benefits of rituximab combined with intravenous immunoglobulin for desensitization in kidney transplant recipients. Transplantation. 2014 Aug 15;98(3):312-9. doi: 10.1097/TP.0000000000000064.
citation: Kahwaji J, Jordan SC, Najjar R, Wongsaroj P, Choi J, Peng A, Villicana R, Vo A. Six-year outcomes in broadly HLA-sensitized living donor transplant recipients desensitized with intravenous immunoglobulin and rituximab. Transpl Int. 2016 Dec;29(12):1276-1285. doi: 10.1111/tri.12832. Epub 2016 Oct 24.
citation: Klein K, Susal C, Schafer SM, Becker LE, Beimler J, Schwenger V, Zeier M, Schemmer P, Macher-Goeppinger S, Scherer S, Opelz G, Morath C. Living donor kidney transplantation in patients with donor-specific HLA antibodies enabled by anti-CD20 therapy and peritransplant apheresis. Atheroscler Suppl. 2013 Jan;14(1):199-202. doi: 10.1016/j.atherosclerosissup.2012.10.030.
citation: Rostaing L, Maggioni S, Hecht C, Hermelin M, Faudel E, Kamar N, Sallusto F, Doumerc N, Allal A. Efficacy and safety of tandem hemodialysis and immunoadsorption to desensitize kidney transplant candidates. Exp Clin Transplant. 2015 Apr;13 Suppl 1:165-9.
citation: Kauke T, Klimaschewski S, Schoenermarck U, Fischereder M, Dick A, Guba M, Stangl M, Werner J, Meiser B, Habicht A. Outcome after Desensitization in HLA or ABO-Incompatible Kidney Transplant Recipients: A Single Center Experience. PLoS One. 2016 Jan 5;11(1):e0146075. doi: 10.1371/journal.pone.0146075. eCollection 2016.