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

March 26, 2020 updated by: University Hospital, Grenoble
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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

8

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • La Tronche, France
        • Grenoble Alpes University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: OTHER
  • Allocation: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
OTHER: Desensitization with Tocilizumab and rituximab (MFI >15000)
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).
Drug: Rituximab 375 mg/m2 at Day-30
Rituximab 375 mg/m2 at Day-30
Drug: Rituximab 375 mg/m2 at Day-15 (only for donors living)
Rituximab 375 mg/m2 at Day-15
Other: Transplant Day-0
TRANSPLANTATION
OTHER: Desensitization with Rituximab only (MFI<15000)
Drug: Rituximab 375 mg/m2 at Day-30
Rituximab 375 mg/m2 at Day-30
Drug: Rituximab 375 mg/m2 at Day-15 (only for donors living)
Rituximab 375 mg/m2 at Day-15
Other: Transplant Day-0
TRANSPLANTATION

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Description of the results of the strategy of desensitization in patients who will access to kidney transplantation from deceased or living donors.
Time Frame: at day 1 start of desensitization, at day 0 of Graft
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Desensitization efficacy with regards to DSA decrease and kidney transplantation
Time Frame: Day-198, at day-30 Graft, at day-15, at day0 of Graft,
MFI for highest DSAs for each group
Day-198, at day-30 Graft, at day-15, at day0 of Graft,
impairment of DSA synthesis
Time Frame: Day-198, at day-30 Graft, at day-15, at day0 of Graft,
Decrease in peripheral plasma cells and plasmablasts of >50%
Day-198, at day-30 Graft, at day-15, at day0 of Graft,
Impairment of immune response
Time Frame: Day-198, at day-30 Graft, at day-15, at day0 of Graft,
Decrease in complement factors of >25%
Day-198, at day-30 Graft, at day-15, at day0 of Graft,
Incidence of treatment desensitization protocols, emergent adverse events (safety and Tolerability)
Time Frame: Day-198, at day-30 Graft, at day-15
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Grenoble

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

July 1, 2018

Primary Completion (ACTUAL)

November 21, 2019

Study Completion (ACTUAL)

November 21, 2019

Study Registration Dates

First Submitted

March 23, 2018

First Submitted That Met QC Criteria

April 24, 2018

First Posted (ACTUAL)

April 25, 2018

Study Record Updates

Last Update Posted (ACTUAL)

March 30, 2020

Last Update Submitted That Met QC Criteria

March 26, 2020

Last Verified

March 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 38RC17.247

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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