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

Primary Purpose

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

Status

Terminated

Phase

Not Applicable

Locations

France

Study Type

Interventional

Intervention

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

Rituximab 375 mg/m2 at Day-30

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

Transplant Day-0

About this trial

This is an interventional other trial for End-stage Renal Disease focused on measuring Anti-HLA alloantibodies, Desensitization therapy, Tocilizumab, Rituximab

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

Grenoble Alpes University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Arm Label

Desensitization with Tocilizumab and rituximab (MFI >15000)

Desensitization with Rituximab only (MFI<15000)

Arm Description

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Desensitization efficacy with regards to DSA decrease and kidney transplantation

MFI for highest DSAs for each group

impairment of DSA synthesis

Decrease in peripheral plasma cells and plasmablasts of >50%

Impairment of immune response

Decrease in complement factors of >25%

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.

Full Information

NCT ID

NCT03507348

First Posted

March 23, 2018

Last Updated

March 26, 2020

Sponsor

University Hospital, Grenoble

1. Study Identification

Unique Protocol Identification Number

NCT03507348

Brief Title

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

2. Study Status

Record Verification Date

March 2020

Overall Recruitment Status

Terminated

Why Stopped

investigateur decision

Study Start Date

July 1, 2018 (Actual)

Primary Completion Date

November 21, 2019 (Actual)

Study Completion Date

November 21, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University Hospital, Grenoble

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

Keywords

Anti-HLA alloantibodies, Desensitization therapy, Tocilizumab, Rituximab

7. Study Design

Primary Purpose

Other

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

8 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Desensitization with Tocilizumab and rituximab (MFI >15000)

Arm Type

Other

Arm Title

Desensitization with Rituximab only (MFI<15000)

Arm Type

Other

Intervention Type

Drug

Intervention Name(s)

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

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Rituximab 375 mg/m2 at Day-30

Intervention Description

Rituximab 375 mg/m2 at Day-30

Intervention Type

Drug

Intervention Name(s)

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

Intervention Description

Rituximab 375 mg/m2 at Day-15

Intervention Type

Other

Intervention Name(s)

Transplant Day-0

Intervention Description

TRANSPLANTATION

Primary Outcome Measure Information:

Title

Description of the results of the strategy of desensitization in patients who will access to kidney transplantation from deceased or living donors.

Description

Decrease of MFI for highest donor-specific alloantibody (DSA) between start and end of desensitization for every patient in each category

Time Frame

at day 1 start of desensitization, at day 0 of Graft

Secondary Outcome Measure Information:

Title

Desensitization efficacy with regards to DSA decrease and kidney transplantation

Description

MFI for highest DSAs for each group

Time Frame

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

Title

impairment of DSA synthesis

Description

Decrease in peripheral plasma cells and plasmablasts of >50%

Time Frame

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

Title

Impairment of immune response

Description

Decrease in complement factors of >25%

Time Frame

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

Title

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

Description

Emergent adverse events to the desensitization therapy will be carefully monitored during the treatment period and within the following three months.

Time Frame

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

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.

Facility Information:

Facility Name

Grenoble Alpes University Hospital

City

La Tronche

Country

France

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

27468073

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.

Results Reference

result

PubMed Identifier

21793744

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.

Results Reference

result

PubMed Identifier

24770617

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.

Results Reference

result

PubMed Identifier

27529314

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.

Results Reference

result

PubMed Identifier

23357165

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.

Results Reference

result

PubMed Identifier

25894148

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.

Results Reference

result

PubMed Identifier

26730981

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.

Results Reference

result

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

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