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SensitisationPhase 2COMBATNCT05145296

The Safety/Efficacy Of Daratumumab With Belatacept In Highly HLA-Sensitized Patients Awaiting Kidney Transplantation

A Phase 2 study testing Each patient will undergo in the first step of the study belatacept treatment and in the second apheresis and daratumumab in people with Sensitisation and Highly Sensitised Dialysis Patients, 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

While the number of kidney transplants is increasing worldwide every year, there is a clear imbalance between the high number of patients in the waiting list and those receiving a transplant and importantly, among waitlist patients there is a progressively higher number of highly sensitised patients that have very low… Read more about this study

Who is it for?
Ages 18 to 70 years
What is being tested?
Each patient will undergo in the first step of the study belatacept treatment and in the second apheresis and daratumumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
5 participants
Where
1 siteFrance
Study dates
19 Jan 2022to 10 Oct 2025
Phase
Phase 2
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 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Males and females age 18-70 years
  • End Stage Renal Disease (ESRD) on dialysis
  • Patient listed and active for a deceased donor kidney transplant and have not received compatible donor offer for ≥3 year.
  • Calculated PRA ≥ 99%
  • Positive CMV serology
  • Positive EBV serology
  • Current vaccination for more than one month for diphtheria, tetanus, poliomyelitis, influenza, pneumococcus, meningococcus, herpes zoster and SARS CoV-2.
  • Patient affiliated to social security insurance or beneficiary of social security insurance

Who cannot join

  • Inability or unwillingness of a participant to give written informed consent or comply with study protocol
  • Known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infections (including HIV, hepatitis B, hepatitis C, zoster)
  • Patient with positive hepatitis core antigen and/or positive hepatitis B surface antigen
  • Serious uncontrolled concomitant major organ disease
  • Any infection requiring hospitalization and intravenous antibiotics within 4 weeks of screening or Per os antibiotics within 2 weeks
  • Primary or secondary immunodeficiency
Show all 24Show fewer
  • History of active tuberculosis (TB) (even if treated) or untreated latent TB
  • Malignancy within the last 5 years except documented and treated basal and squamous cell cancer of the skin
  • Alcohol, drug or chemical abuse within 1 year
  • Difficult peripheral venous access
  • Negative EBV serology
  • Negative CMV serology
  • Neutropenia (ANC <1000/uL) or thrombocytopenia (platelet count <100,000/uL) within 4 weeks prior to study entry
  • Patient previously treated with investigational products (belatacept, daratumumab)
  • Severe allergic or anaphylactic reactions to human, humanized or murine monoclonal antibodies
  • Hypersensitivity to any active substance or component of the investigational medicinal products
  • Any contra-indication to premedication drugs (paracetamol, dexchlorpheniramine, cetirizine, dexamethasone, montelukast) or post-medication drugs (corticosteroids, bronchodilators, valaciclovir)
  • Immunization with live vaccine within 2 months of study entry
  • Dry body weight ≥75kg.
  • Pregnancy or lactation
  • Females with childbearing status, defined as a premenopausal female capable of becoming pregnant, and not using an effective form of birth control. Effective birth control methods include oral, implant or patch hormone contraception; intrauterine device; abstinence and outercourse; tubal ligation; vasectomy.
  • Participant involved in another interventional clinical study
  • Person deprived of liberty by judicial order
  • Person under guardianship or curatorship

Trial locations and contacts

1 site in 1 country.

France1 site

  • Chu Grenoble

    La Tronche, 38700

Other trials in France

About this study

Official title: Non-Randomized, Single-Center Pilot Trial Assessing The Safety/Efficacy Of Targeting Peripheral And Central Humoral Alloimmune Memory With Daratumumab And With Belatacept In Highly HLA-Sensitized Patients Awaiting Kidney Transplantation

While the number of kidney transplants is increasing worldwide every year, there is a clear imbalance between the high number of patients in the waiting list and those receiving a transplant and importantly, among waitlist patients there is a progressively higher number of highly sensitised patients that have very low or even no chance to receive a compatible organ. These patients remain for very long periods of time on dialysis therapy, having lower quality of life, lower life expectancy and produce higher health-related costs. Unfortunately, current desensitization therapies have shown very poor success and patients usually lose these grafts very fast if transplanted across a positive cross-match. Therefore, there is an urgent need for novel desensitization strategies capable of overcoming this immunological barrier and allow an increasing number of patients to receive a HLA-compatible kidney allograft.This is a non-randomized, single arm study, combination trial designed according to the Recommendations of the Clinical Trial Design Task Force of the NCI Investigational Drug Steering Committee. The study will enroll 12 patients with cPRA or TGI ≥99% on the deceased donor kidney transplant waiting list, who have not received a compatible donor offer for >3 year. According to inclusion and exclusion criteria patients will be screened to participate in the trial.

Read the detailed description

This is a non-randomized, single arm study, combination trial designed according to the Recommendations of the Clinical Trial Design Task Force of the NCI Investigational Drug Steering Committee. The study will enroll 12 patients with cPRA or TGI ≥99% on the deceased donor kidney transplant waiting list, who have not received a compatible donor offer for >3 year. According to inclusion and exclusion criteria patients will be screened to participate in the trial.

Being tested
Each patient will undergo in the first step of the study belatacept treatment and in the second apheresis and daratumumab
Keywords
Highly sensitized kidney transplant, Desensitization, BELATACEPT, Daratumumab

What participants receive

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

  • Each patient will undergo in the first step of the study belatacept treatment and in the second apheresis and daratumumabCombination product

    Also called combination trial designed

    Four consecutive cohorts each comprising 3 patients are planned. STEP I: Patients receive Belatacept 10mg/kg, administered on days 1, 5, end of week 2, 4 and 8 .

    Patients without a significant decrease in the global cPRA (cPRA or TGI ≥99%) or significant reduction of anti-HLA Ab MF will continue to the second step.

    STEP II: (15 weeks) One week after the last injection of belatacept, patients will undergo 4 sessions of apheresis (plasmapheresis (PF) or Immunoadsorption (IA)) which will be given every 48h. At week 11, patients will receive 4 doses of daratumumab (8mg/kg) every two weeks until week 17. Daratumumab will be alternated with 4 additional doses of belatacept 5 mg/kg FOLLOW-UP (24 weeks) All patients exiting the study, either having completed all treatment courses or exiting prematurely (transplanted or not), will be proposed monthly follow-up visits

Study groups in NCT05145296
Study groupRoleWhat they receive
Patients with cPRA ≥99%OtherThis is a non-randomized, single arm study, combination trial designed according to the Recommendations of the Clinical Trial Design Task Force of the NCI Investigational Drug Steering Committee. The study will enroll 12 patients with cPRA ≥99% on the deceased donor kidney transplant waiting list, who have not received a compatible donor offer for >3 year. According to inclusion and exclusion criteria patients will be screened to participate in the trial.
Receives: Combination Product: Each patient will undergo in the first step of the study belatacept treatment and in the second apheresis and daratumumab

What is being measured

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

  1. Proportion of severe or medically significant Adverse and Serious Adverse Events

    Proportion of severe or medically significant Adverse and Serious Adverse Events, defined by:

    Any grade 3 or higher infection (according to the CTCAE definition, i.e. IV antibiotic, antifungal, or antiviral intervention indicated; or invasive intervention indicated) during the interventional study period (6 months).

    Success will be defined by a proportion of toxicity below 17% (≤2/12).

    Measured: end of study

Secondary outcomes (12)

  1. Assess the efficacy of dual targeting with anti-CD38 mAb daratumumab (Darzalex®) and co-stimulation blockade with belatacept (Nulojix®) in HLA-sensitized patients

    Proportion of patients in whom ≥10 HLA antibodies (class I and/or class II) are eliminated (undetectable or <2000 MFI) OR cPRA(or TGI) decrease to <99% at the end of step I and at the end of step II.

    Success will be defined by an efficacy of 66% (≥8/12)

    Measured: end of study

  2. Evaluate the impact of belatacept on anti-HLA antibody reduction using single antigen beads (SAB) in terms of MFI and specificities

    Total number and mean number of HLA antibodies at the end of Step I (belatacept) as compared to baseline

    Measured: Week 9

  3. Evaluate the impact of belatacept on circulating Tfh cells compared to baseline belatacept therapy and at the end of this therapy (Step I).

    Change in number and percentages of subtypes of circulating Peripheral T helper cells (TPH) including Tfh cells at the end of belatacept therapy

    Measured: week 9 compared to baseline

  4. Evaluate the impact of belatacept on circulating HLA-specific mBC and their capacity to produce anti-HLA antibodies as well as numbers function of HLA-specific LLPC in bone marrow compared to baseline therapy and at the end of this therapy (Step I)

    Proportion of patients with a reduction of circulating HLA-specific memory B cells (both class I and class II)

    Measured: Week 9

  5. Evaluate the impact of the dual combination of belatacept and daratumumab on anti-HLA antibody reduction using single antigen beads (SAB) in terms of MFI and specificities

    Change in number and mean number of HLA antibodies at the end of Step II (belatacept followed by daratumumab)

    Measured: week 24 compared to baseline

  6. Evaluate the impact of the dual combination of belatacept and daratumumab on circulating Tfh cells compared to baseline and the end of this dual therapy and at the time of a kidney transplantation, if any (Step II).

    Change in number and percentages of subtypes of circulating Tfh cells at the end of dual therapy and at the time of an kidney transplantation as compared to baseline

    Measured: week 24 compared to baseline

  7. Evaluate the impact of the dual combination of belatacept and daratumumab on circulating HLA-specific mBc and their capacity to produce anti-HLA antibodies as well as numbers and function of LLPC in bone marrow compared to baseline and the end of this

    Proportion of patients with a reduction of circulating HLA-specific memory B cells (both class I and class II)

    Measured: week 24

  8. Evaluate the impact of the dual combination of belatacept and daratumumab on immunodominant HLA antibody (class I and Class II) at the end Step II as compared to baseline and as compared to the end of Step I

    Mean reduction in MFI of the immunodominant HLA antibody, class I and Class II at the end Step II

    Measured: week 24

  9. Evaluate the impact of the dual combination of belatacept and daratumumab on HLA-specific Antibody secreting cells (ASC) frequencies in bone marrow aspirates at the end of Step II as compared to baseline

    Proportion of patients with a reduction of HLA-specific ASC frequencies in bone marrow aspirates

    Measured: week 24

  10. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

    Number of participants with treatment-related adverse events as assessed by CTCAE v4.0'

    Measured: End of study

  11. Evaluate the impact of the dual combination of belatacept and daratumumab on patients transplanted with a compatible donor

    Proportion of patients transplanted with a compatible donor

    Measured: week 18, week 24

  12. In case of kidney transplantation, investigate the germinal center activation of iliac lymph nodes obtained at the time of kidney transplantation

    At the time of kidney transplantation investigate the germinal center activation of iliac lymph nodes obtained during surgery

    Measured: day of transplantation

Timeline

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

  1. First posted6 Dec 2021
  2. Study start19 Jan 2022
  3. Primary completion1 Dec 2024
  4. Study completion10 Oct 2025

Why it stopped: limited clinically significant reduction on global cPRA levels (access to transplantation was unchanged), as well as restrictions in belatacept supply.

Resources

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
5 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05145296
Sponsor's protocol ID
38RC21.171
Acronym
COMBAT
Status last verified
May 2023
First submitted
21 Oct 2021
Last updated
10 Dec 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Loupy A, Lefaucheur C. Antibody-Mediated Rejection of Solid-Organ Allografts. N Engl J Med. 2018 Sep 20;379(12):1150-1160. doi: 10.1056/NEJMra1802677. No abstract available.

    PubMed 30231232

  • Pruthi R, Hilton R, Pankhurst L, Mamode N, Hudson A, Roderick P, Ravanan R. UK Renal Registry 16th annual report: chapter 4 demography of patients waitlisted for renal transplantation in the UK: national and centre-specific analyses. Nephron Clin Pract. 2013;125(1-4):81-98. doi: 10.1159/000360023. Epub 2014 Feb 14.

    PubMed 24662168

  • Wiebe C, Tambur A, Nickerson PW. A call to action-The transplant recipient's expectation of precision in transplant medicine. Am J Transplant. 2018 Dec;18(12):2845-2846. doi: 10.1111/ajt.15027. Epub 2018 Aug 13. No abstract available.

    PubMed 30022602

  • Kiernan JJ, Ellison CA, Tinckam KJ. Measuring alloantibodies: a matter of quantity and quality. Curr Opin Organ Transplant. 2019 Feb;24(1):20-30. doi: 10.1097/MOT.0000000000000593.

    PubMed 30507703

  • Djamali A, Kaufman DB, Ellis TM, Zhong W, Matas A, Samaniego M. Diagnosis and management of antibody-mediated rejection: current status and novel approaches. Am J Transplant. 2014 Feb;14(2):255-71. doi: 10.1111/ajt.12589. Epub 2014 Jan 8.

    PubMed 24401076

  • Formica RN Jr, Kulkarni S. Being Thoughtful about Desensitization. Clin J Am Soc Nephrol. 2017 Nov 7;12(11):1878-1880. doi: 10.2215/CJN.09000817. Epub 2017 Oct 3. No abstract available.

    PubMed 28974523

  • Cornell LD, Schinstock CA, Gandhi MJ, Kremers WK, Stegall MD. Positive crossmatch kidney transplant recipients treated with eculizumab: outcomes beyond 1 year. Am J Transplant. 2015 May;15(5):1293-302. doi: 10.1111/ajt.13168. Epub 2015 Mar 2.

    PubMed 25731800

  • Luque S, Lucia M, Crespo E, Jarque M, Grinyo JM, Bestard O. A multicolour HLA-specific B-cell FluoroSpot assay to functionally track circulating HLA-specific memory B cells. J Immunol Methods. 2018 Nov;462:23-33. doi: 10.1016/j.jim.2018.07.011. Epub 2018 Jul 31.

    PubMed 30075182

  • Lucia M, Luque S, Crespo E, Melilli E, Cruzado JM, Martorell J, Jarque M, Gil-Vernet S, Manonelles A, Grinyo JM, Bestard O. Preformed circulating HLA-specific memory B cells predict high risk of humoral rejection in kidney transplantation. Kidney Int. 2015 Oct;88(4):874-87. doi: 10.1038/ki.2015.205. Epub 2015 Jul 15.

    PubMed 26176829

  • Perry DK, Pollinger HS, Burns JM, Rea D, Ramos E, Platt JL, Gloor JM, Stegall MD. Two novel assays of alloantibody-secreting cells demonstrating resistance to desensitization with IVIG and rATG. Am J Transplant. 2008 Jan;8(1):133-43. doi: 10.1111/j.1600-6143.2007.02039.x.

    PubMed 18184311

  • Moreno Gonzales MA, Gandhi MJ, Schinstock CA, Moore NA, Smith BH, Braaten NY, Stegall MD. 32 Doses of Bortezomib for Desensitization Is Not Well Tolerated and Is Associated With Only Modest Reductions in Anti-HLA Antibody. Transplantation. 2017 Jun;101(6):1222-1227. doi: 10.1097/TP.0000000000001330.

    PubMed 27379560

  • Kwun J, Burghuber C, Manook M, Iwakoshi N, Gibby A, Hong JJ, Knechtle S. Humoral Compensation after Bortezomib Treatment of Allosensitized Recipients. J Am Soc Nephrol. 2017 Jul;28(7):1991-1996. doi: 10.1681/ASN.2016070727. Epub 2017 Feb 23.

    PubMed 28232617

  • Chen J, Yin H, Xu J, Wang Q, Edelblum KL, Sciammas R, Chong AS. Reversing endogenous alloreactive B cell GC responses with anti-CD154 or CTLA-4Ig. Am J Transplant. 2013 Sep;13(9):2280-92. doi: 10.1111/ajt.12350. Epub 2013 Jul 15.

    PubMed 23855587

  • Yang J, Chen J, Young JS, Wang Q, Yin D, Sciammas R, Chong AS. Tracing Donor-MHC Class II Reactive B cells in Mouse Cardiac Transplantation: Delayed CTLA4-Ig Treatment Prevents Memory Alloreactive B-Cell Generation. Transplantation. 2016 Aug;100(8):1683-91. doi: 10.1097/TP.0000000000001253.

    PubMed 27362308

  • Kim EJ, Kwun J, Gibby AC, Hong JJ, Farris AB 3rd, Iwakoshi NN, Villinger F, Kirk AD, Knechtle SJ. Costimulation blockade alters germinal center responses and prevents antibody-mediated rejection. Am J Transplant. 2014 Jan;14(1):59-69. doi: 10.1111/ajt.12526.

    PubMed 24354871

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Each patient will undergo in the first step of the study belatacept treatment and in the second apheresis and daratumumab in people with Sensitisation and Highly Sensitised Dialysis Patients, run by University Hospital, Grenoble at 1 site in France.

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 8 inclusion and 24 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 10 Dec 2025. 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.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: limited clinically significant reduction on global cPRA levels (access to transplantation was unchanged), as well as restrictions in belatacept supply.). 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?

Proportion of severe or medically significant Adverse and Serious Adverse Events (time frame: end of study). 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 NCT05145296, which also lists 26 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 10 Dec 2025.

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