End-stage Renal DiseaseNCT03507348

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

A study testing visits of tocilizumab injection (every 4 weeks, up to 5 visits), Rituximab 375 mg/m2 at Day-30 and Rituximab 375 mg/m2 at Day-15 (only for donors living) in people with End-stage Renal Disease and Kidney Transplantation, run by University Hospital, Grenoble at 1 site in France.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages 18 to 65 years
Conditions the study is for: End-stage Renal Disease, Kidney Transplantation, Hla-incompatible Kidney Transplant Candidates
What is being tested?: visits of tocilizumab injection (every 4 weeks, up to 5 visits), Rituximab 375 mg/m2 at Day-30 and Rituximab 375 mg/m2 at Day-15 (only for donors living)
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 8 participants
Where: 1 siteFrance
Study dates: 1 Jul 2018to 21 Nov 2019
Phase: Interventional
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Show all 9Show fewer

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

Who cannot join

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.

Trial locations and contacts

1 site in 1 country.

France1 site

Grenoble Alpes University Hospital
La Tronche

Other trials in France

About this study

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
Being tested: 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
Keywords: Anti-HLA alloantibodies, Desensitization therapy, Tocilizumab, Rituximab
Medical subject headings: Kidney Failure, Chronic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

Study groups in NCT03507348
Study group	Role	What they receive
Desensitization with Tocilizumab and rituximab (MFI >15000)	Other	Not described Receives: 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	Not described Receives: Drug: Rituximab 375 mg/m2 at Day-30; Drug: Rituximab 375 mg/m2 at Day-15 (only for donors living); Other: Transplant Day-0

What is being measured

The primary outcome is the main question the study is designed to answer.

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

Secondary outcomes (4)

Desensitization efficacy with regards to DSA decrease and kidney transplantation
MFI for highest DSAs for each group
Measured: Day-198, at day-30 Graft, at day-15, at day0 of Graft,
impairment of DSA synthesis
Decrease in peripheral plasma cells and plasmablasts of >50%
Measured: Day-198, at day-30 Graft, at day-15, at day0 of Graft,
Impairment of immune response
Decrease in complement factors of >25%
Measured: Day-198, at day-30 Graft, at day-15, at day0 of Graft,
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.
Measured: Day-198, at day-30 Graft, at day-15

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Jul 201821 Nov 2019

First posted25 Apr 2018
Study start1 Jul 2018
Primary completion21 Nov 2019
Study completion21 Nov 2019

Why it stopped: investigateur decision

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (7)Papers the sponsor has linked to this study.
Other trials for End-stage Renal DiseaseStudies of the same condition, open and under way.
More trials run by University Hospital, GrenobleThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Other
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 8 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03507348
Sponsor's protocol ID: 38RC17.247
Status last verified: Mar 2020
First submitted: 23 Mar 2018
Last updated: 30 Mar 2020
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

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.
PubMed 27468073
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.
PubMed 21793744
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.
PubMed 24770617
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.
PubMed 27529314
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.
PubMed 23357165
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.
PubMed 25894148
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.
PubMed 26730981

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 30 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Evaluation of Desensitization Protocols in HLA-incompatible Kidney-transplant Candidates
ClinicalTrials.gov ID: NCT03507348
Acronym / sponsor ID: 38RC17.247
Conditions: End-stage Renal Disease, Kidney Transplantation, Hla-incompatible Kidney Transplant Candidates
Keywords: Anti-HLA alloantibodies, Desensitization therapy, Tocilizumab, Rituximab
Study type: Interventional
Recruitment status: TerminatedReason stopped: investigateur decision
Enrolment: 8 participants (actual)
Lead sponsor: University Hospital, GrenobleUniversity, hospital or other
Study start: 1 Jul 2018 (actual)
Primary completion: 21 Nov 2019 (actual)
Study completion: 21 Nov 2019 (actual)
First posted: 25 Apr 2018 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Other
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
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

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (9 listed)

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

Key exclusion criteria (7 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
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	Desensitization with Tocilizumab and rituximab (MFI >15000)
Rituximab 375 mg/m2 at Day-30Rituximab 375 mg/m2 at Day-30	Drug	Desensitization with Rituximab only (MFI<15000), Desensitization with Tocilizumab and rituximab (MFI >15000)
Rituximab 375 mg/m2 at Day-15 (only for donors living)Rituximab 375 mg/m2 at Day-15	Drug	Desensitization with Rituximab only (MFI<15000), Desensitization with Tocilizumab and rituximab (MFI >15000)
Transplant Day-0TRANSPLANTATION	Other	Desensitization with Rituximab only (MFI<15000), Desensitization with Tocilizumab and rituximab (MFI >15000)

Primary outcome

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

4 secondary outcomes

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,
impairment of DSA synthesis
Time frame: 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,
Incidence of treatment desensitization protocols, emergent adverse events (safety and Tolerability)
Time frame: Day-198, at day-30 Graft, at day-15

Results and safety

The study was stopped early (reason given: investigateur decision). Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2020.
Results publication: PubMed 27468073Orandi 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 publication: PubMed 21793744Montgomery 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 publication: PubMed 24770617Vo 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 publication: PubMed 27529314Kahwaji 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 publication: PubMed 23357165Klein 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 publication: PubMed 25894148Rostaing 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 publication: PubMed 26730981Kauke 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.
Individual participant dataSharing planned: No

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Recruiting
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 30 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study was stopped early (reason given: investigateur decision). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03507348, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Mar 2020.