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

Kidney Transplantation Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03507348
• Other study ID #: 38RC17.247
• Status: Terminated
• Phase: N/A
• Start date: July 1, 2018
• Est. completion date: November 21, 2019

Study information

• Verified date: March 2020
• Source: University Hospital, Grenoble
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 8
• Est. completion date: November 21, 2019
• Est. primary completion date: November 21, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• End-stage Renal Disease
• Hla-incompatible Kidney Transplant Candidates
• Kidney Failure, Chronic
• Kidney Transplantation

Intervention

Drug:
• visits of tocilizumab injection (every 4 weeks, up to 5 visits)
every 4 weeks, up to 5 visits (D-170, D-142, D-114, D-86, D-58).
• Rituximab 375 mg/m2 at Day-30
Rituximab 375 mg/m2 at Day-30
• Rituximab 375 mg/m2 at Day-15 (only for donors living)
Rituximab 375 mg/m2 at Day-15

Other:
• Transplant Day-0
TRANSPLANTATION

Locations

Country	Name	City	State
France	Grenoble Alpes University Hospital	La Tronche

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Grenoble

Country where clinical trial is conducted

France, 

References & Publications (7)

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):1276-12 — View 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 — View Citation

Klein K, Süsal C, Schäfer 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 pe — View 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 — View 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. — View 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. — View 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( — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Description of the results of the strategy of desensitization in patients who will access to kidney transplantation from deceased or living donors.	Decrease of MFI for highest donor-specific alloantibody (DSA) between start and end of desensitization for every patient in each category	at day 1 start of desensitization, at day 0 of Graft
Secondary	Desensitization efficacy with regards to DSA decrease and kidney transplantation	MFI for highest DSAs for each group	Day-198, at day-30 Graft, at day-15, at day0 of Graft,
Secondary	impairment of DSA synthesis	Decrease in peripheral plasma cells and plasmablasts of >50%	Day-198, at day-30 Graft, at day-15, at day0 of Graft,
Secondary	Impairment of immune response	Decrease in complement factors of >25%	Day-198, at day-30 Graft, at day-15, at day0 of Graft,
Secondary	Incidence of treatment desensitization protocols, emergent adverse events (safety and Tolerability)	Emergent adverse events to the desensitization therapy will be carefully monitored during the treatment period and within the following three months.	Day-198, at day-30 Graft, at day-15