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

NCT03507348 | Terminated

• 1 other identifier: 38RC17.247
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

Anti-HLA alloantibodies; Desensitization therapy; Tocilizumab; Rituximab

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Desensitization efficacy with regards to DSA decrease and kidney transplantation

  Day-198, at day-30 Graft, at day-15, at day0 of Graft,

• impairment of DSA synthesis

  Day-198, at day-30 Graft, at day-15, at day0 of Graft,

• Impairment of immune response

  Day-198, at day-30 Graft, at day-15, at day0 of Graft,

• Incidence of treatment desensitization protocols, emergent adverse events (safety and Tolerability)

  Day-198, at day-30 Graft, at day-15

Study Arms (2)

Desensitization with Tocilizumab and rituximab (MFI >15000)

OTHER

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

Desensitization with Rituximab only (MFI<15000)

OTHER

Drug: Rituximab 375 mg/m2 at Day-30; Drug: Rituximab 375 mg/m2 at Day-15 (only for donors living); Other: Transplant Day-0

Interventions

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

every 4 weeks, up to 5 visits (D-170, D-142, D-114, D-86, D-58).

Desensitization with Tocilizumab and rituximab (MFI >15000)

Rituximab 375 mg/m2 at Day-30 DRUG

Rituximab 375 mg/m2 at Day-30

Desensitization with Rituximab only (MFI<15000); Desensitization with Tocilizumab and rituximab (MFI >15000)

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

Rituximab 375 mg/m2 at Day-15

Desensitization with Rituximab only (MFI<15000); Desensitization with Tocilizumab and rituximab (MFI >15000)

Transplant Day-0 OTHER

TRANSPLANTATION

Desensitization with Rituximab only (MFI<15000); Desensitization with Tocilizumab and rituximab (MFI >15000)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Active underlying infections or neoplasia
• Pregnant women, parturient or breastfeeding
• 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.

Sponsors & Collaborators

• University Hospital, Grenoble: lead

Study Sites (1)

Grenoble Alpes University Hospital

La Tronche, France

Location

Related Publications (7)

• 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.

  PMID: 27468073 RESULT

• 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.

  PMID: 21793744 RESULT

• 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.

  PMID: 24770617 RESULT

• 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.

  PMID: 27529314 RESULT

• 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.

  PMID: 23357165 RESULT

• 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.

  PMID: 25894148 RESULT

• 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.

  PMID: 26730981 RESULT

MeSH Terms

Conditions

Kidney Failure, Chronic

Interventions

Rituximab; Single Person

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Marital Status; Family Characteristics; Demography; Population Characteristics; Socioeconomic Factors

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2018
• First Posted: April 25, 2018
• Study Start: July 1, 2018
• Primary Completion: November 21, 2019
• Study Completion: November 21, 2019
• Last Updated: March 30, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)