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Highly Sensitized Prospective Kidney Transplant RecipientsPhase 1/2ADAPTNCT05017545

Carfilzomib and Belatacept for Desensitization

A Phase 1/2 study testing carfilzomib, belatacept and Bone marrow aspiration in people with Highly Sensitized Prospective Kidney Transplant Recipients, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

Some kidney transplant candidates have a very low chance of getting a kidney transplant because their immune systems are "highly sensitized" to most kidney donors. Being "highly sensitized" means that they will likely have to wait a long time (more than 5 years) before an acceptable donor is found for them or, they… Read more about this study

Who is it for?
Ages 18 to 65 years
What is being tested?
carfilzomib, belatacept and Bone marrow aspiration
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
1 siteUnited States
Study dates
28 Dec 2021to Apr 2027
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

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

  • Individuals who meet all of the following criteria are eligible for enrollment as study subjects-
  • Subject must be able to understand and provide informed consent
  • End stage renal disease (ESRD) on dialysis
  • United Network for Organ Sharing (UNOS) listed for a kidney transplant with any one of the following:
  • Current calculated panel reactive antibodies (cPRA) ≥ 99.9 percent awaiting deceased donor transplant
  • Current cPRA >98 percent (with >5 years of waiting time) awaiting deceased donor transplant
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  • Current cPRA >98 percent with Human Leukocyte Antigen (HLA)-incompatible approved living donor and has not received a transplant after 1 year in a kidney paired exchange program
  • Evidence of established immunity to Epstein-Barr virus (EBV) as demonstrated by serologic testing
  • Negative result of most recent tuberculosis (TB) testing or appropriately completed latent tuberculosis infection (LTBI) therapy.
  • Testing should be conducted using either a purified protein derivative (PPD) or interferon-gamma release assay (i.e. QuantiFERON-TB, T-SPOT.TB).
  • Negative results from tests performed within 12 months prior to study entry are acceptable in the absence of any intervening exposure to TB.
  • Subjects with a positive test result must have completed appropriate therapy for LTBI.
  • Note: LTBI treatment regimens should be among those endorsed by the Centers for Disease Control and Prevention (CDC), url: https://www.cdc.gov/tb/topic/treatment/ltbi.htm
  • Negative Food and Drug Administration (FDA)-approved test for human immunodeficiency virus (HIV) diagnosis (at screening or as documented in medical record, up to 6 months prior to screening)
  • Negative Hepatitis C antibody test at screening or as documented in medical record, up to 6 months prior to screening.
  • --If there is a history of treated hepatitis C then documentation of two consecutive negative HCV quantitative ribonucleic acid (RNA) polymerase chain reaction (PCR) tests separated by at least 6 months is required. Untreated subjects with positive HCV antibody and a single negative HCV quantitative HCV RNA are eligible.
  • Negative result for SARS-CoV-2 by an FDA-authorized molecular diagnostic test. Examples include, but are not limited to RT-PCR, LAMP, TMA, and qSTAR. Candidates with a history of recent COVID infection may proceed despite a positive result if they have had complete clinical recovery and it has been >/= 21 days since the initial diagnosis.
  • Subjects must have an echocardiogram within the previous 1 year without any of the following findings:
  • severe left ventricular hypertrophy (LVH)
  • greater than mild LVH accompanied by diastolic dysfunction
  • left ventricular ejection fraction <40 percent
  • pulmonary hypertension defined as right ventricular systolic pressure >35 mm Hg or tricuspid regurgitant velocity >2.8 m/s
  • Female subjects of reproductive potential must have a negative pregnancy test upon study entry
  • All subjects of reproductive potential must agree to use contraception for the duration of the study
  • Subjects must have current vaccinations or documented immunity to:
  • varicella (chickenpox)
  • measles
  • hepatitis B
  • pneumococcus
  • influenza, and
  • varicella zoster (if ≥ 50 years old).
  • Note: If subjects require administration of either live or killed vaccines to meet eligibility requirements, they must wait at least 2 weeks between vaccination and the baseline visit (i.e., at least 4 weeks before initiation of therapy)
  • Living Donor Inclusion Criteria:
  • Living donors must meet all of the following criteria to be eligible-
  • Able to understand and provide informed consent for research
  • Meets United Network for Organ Sharing (UNOS) requirements for kidney organ donation

Who cannot join

  • Individuals who meet any of these criteria are not eligible for enrollment as study subjects-
  • Inability or unwillingness of a subject to give written informed consent or comply with study protocol
  • Known active current or history of invasive fungal infection, non-tuberculous mycobacterial infection
  • Hepatitis B surface antigen or core antibody positive
  • Serious uncontrolled concomitant major organ disease, excluding kidney failure
  • Chronic respiratory failure
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  • Uncontrolled systemic hypertension
  • Previous non-kidney solid organ transplant or bone marrow transplant
  • Any infection requiring hospitalization and intravenous (IV) therapy within 4 weeks of screening or oral therapy within 2 weeks of screening
  • Primary or secondary immunodeficiency
  • History of thromboembolism (except thrombosis of dialysis vascular access site)
  • Subjects with myocardial infarction within 12 months of screening or cardiac dysrhythmias uncontrolled by medications
  • History of plasma cell dyscrasia
  • Known bleeding diathesis or coagulation abnormality
  • History of active tuberculosis (TB) (even if treated)
  • Malignancy within the last 5 years except treated basal and squamous cell cancer of the skin or treated cervical cancer in situ
  • Women who are currently pregnant or nursing
  • Alcohol, drug, or chemical abuse within 1 year
  • Treatment with any investigational agent within 4 weeks (or 5 half-lives of investigational drug, whichever is longer) of screening
  • Current treatment with other biological drug. If the potential subject receives standard of care antibody treatments for prophylaxis of COVID-19 (permitted in protocol), there must be a minimum interval of 2 weeks after this treatment and before initiation of the study therapy.
  • Current treatment with any medication which increases the risk of thromboembolic events including oral contraceptives
  • Currently smoking tobacco
  • Neutropenia (absolute neutrophil count <1000/microliter) or thrombocytopenia (platelet count <100,000/microliter) within 4 weeks prior to screening
  • Alanine Aminotransferase (ALT) or aspartate aminotransferase (AST) ≥3 times upper limit of normal (ULN) or total bilirubin ≥ 2 times ULN
  • Past or current medical problems or findings from physical examination or laboratory testing not listed above, which, in the opinion of the investigator, may:
  • pose additional risks from participation in the study
  • interfere with the subject's ability to comply with study requirements, or
  • impact the quality or interpretation of the data obtained from the study.
  • 1. There are no exclusion criteria for living donors.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Duke Transplant Center, Duke University Medical Center

    Durham, North Carolina, 27710

Other trials in United States

About this study

Official title: Measuring the Impact of Carfilzomib and Belatacept on Allogeneic Desensitization in Prospective Kidney Transplant Recipients (ITN089ST)

Some kidney transplant candidates have a very low chance of getting a kidney transplant because their immune systems are "highly sensitized" to most kidney donors. Being "highly sensitized" means that they will likely have to wait a long time (more than 5 years) before an acceptable donor is found for them or, they never receive a compatible donor, and die while on the kidney transplant waitlist.

The purpose of this study is to find out whether two drugs, carfilzomib (Kyprolis®),and belatacept (Nulojix®), can make these kidney transplant candidates less sensitized, and make it easier and quicker to find a kidney donor for them.

Read the detailed description

This study enrolled 21 eligible participants, 18 to 65 years of age, with end stage renal failure on dialysis who are on the waiting list for a deceased donor transplant with calculated panel reactive antibodies (cPRA) ≥99.9% or >98% (with >5 years of waiting time) or, those with cPRA >98% and an human leukocyte antigen (HLA)-incompatible approved living donor who have not received a transplant after 1 year in a paired kidney exchange program. The study will evaluate whether the study treatment is safe and can lower the participant's immune system's sensitization to kidney donors, making it easier to find a well-matched kidney for them.

Participants in the study were enrolled in two consecutive Cohorts. The total duration of participation in the study will be 76 weeks for Cohort 1 and 68 weeks for Cohort 2. Participants who undergo kidney transplantation while enrolled in the study will have 52 weeks of follow up post-transplant.

The duration of participation for living donors is one study visit. Their participation in the study ends upon completion of this study visit.

Being tested
carfilzomib, belatacept, Bone marrow aspiration
Keywords
calculated panel reactive antibodies (cPRA), desensitization therapy, human leukocyte antigen (HLA) desensitization

What participants receive

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

  • carfilzomibBiological

    Also called Kyprolis®

    Administered: Intravenously (IV). Carfilzomib is administered intravenously, on two consecutive days, each week for three weeks per cycle. In this study, subjects will receive 2 cycles of carfilzomib. Dosing for each cycle is based on the recommended dosing for carfilzomib monotherapy in the package insert.

    Carfilzomib is a proteasome inhibitor indicated for the treatment of patients with multiple myeloma. In this study, carfilzomib will be used in highly sensitized subjects without myeloma who are awaiting a kidney transplant.

  • belataceptBiological

    Also called Nulojix®

    Administered: Intravenously (IV). Belatacept is indicated for the prophylaxis of organ rejection in adult patients receiving a kidney transplant. In this study, belatacept will be used in highly sensitized subjects who are awaiting a kidney transplant.

  • Bone marrow aspirationProcedure or surgery

    Subjects will undergo a bone marrow aspiration prior to starting the study regimen and at 16 weeks after starting the study regimen. In subjects who undergo a kidney transplant during the study, another bone marrow aspiration will be done if it has been >4 weeks since the previous bone marrow aspiration.

Study groups in NCT05017545
Study groupRoleWhat they receive
Cohort 1ExperimentalThe two investigational agents used in this study are carfilzomib and belatacept. Per protocol, Carfilzomib administered intravenously: * Cycle 1 will consist of 2 doses in week 4 (Day 28 and 29). If tolerated, the dose will be increased and administered twice a week in weeks 5 (Day 35 and 36) and 6 (Day 42 and 43). * Cycle 2 will consist of a total of 6 doses, administered twice weekly in weeks 12 (Day 84 and 85), 13 (Day 91 and 92) and 14 (Day 98 and 99). Per protocol, Belatacept: -Belatacept will be administered intravenously on days 29 (week 4), 33 (week 5), and weeks 6, 8, 12, 16, then at a lower dose at week 20, 24, 28, 32, 36, 40, 44, 48, 52, and 56. Dosing is based on the recommended dose in the package insert.
Receives: Biological: carfilzomib; Biological: belatacept; Procedure: Bone marrow aspiration
Cohort 2ExperimentalThe enrollment of ten additional subjects and dosing regimen is dependent on the results in Cohort 1.° Per protocol, Carfilzomib administered intravenously: * Cycle 1 will consist of 2 doses in week 4 (Day 28 and 29). If tolerated, the dose will be increased and administered twice a week in weeks 5 (Day 35 and 36) and 6 (Day 42 and 43). * Cycle 2 will consist of a total of 6 doses, administered twice weekly in weeks 12 (Day 84 and 85), 13 (Day 91 and 92) and 14 (Day 98 and 99). Per protocol, Belatacept: -Belatacept will be administered intravenously on days 28 (week 4), 33 (week 5), and weeks 6, 8, 12, 16, then at a lower dose at week 20, 24, 28, 32, 36, 40, 44, 48, 52, and 56. Dosing is based on the recommended dose in the package insert. ° May be modified based on the safety and efficacy analysis of Cohort 1.
Receives: Biological: carfilzomib; Biological: belatacept; Procedure: Bone marrow aspiration

What is being measured

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

  1. Proportion of subjects who do not meet a stopping rule for safety and remain free of all of the following through 20 weeks (Cohort 1) after starting treatment or until receiving a transplant, whichever occurs earlier.

    Proportion of subjects who have not met a subject stopping rule, and remain free of all of the following through Week 26 post treatment initiation or until receiving a transplant, whichever occurs earlier:

    1. Grade 3 or higher infusion reaction,
    2. Grade 3 or higher infections, and
    3. Any malignancy.

    The study site will grade the severity of adverse events experienced by the study subjects according to the criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 (Published November 27, 2017).

    Measured: Up to 26 weeks post treatment initiation

  2. Proportion of subjects who do not meet a stopping rule for safety and remain free of all of the following through Week 24 (Cohort 2) post treatment initiation or until receiving a transplant, whichever occurs earlier.

    Proportion of subjects who have not met a subject stopping rule, and remain free of all of the following through Week 24 post treatment initiation or until receiving a transplant, whichever occurs earlier:

    1. Grade 3 or higher infusion reaction,
    2. Grade 3 or higher infections, and
    3. Any malignancy.

    The study site will grade the severity of adverse events experienced by the study subjects according to the criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 (Published November 27, 2017).

    Measured: Up to 24 weeks post treatment initiation

  3. Proportion of subjects who achieve any one of the following compared to Baseline - Cohort 1

    Proportion of subjects who achieve any one of the following compared to Baseline (Visit 0):

    1. Elimination of one human leukocyte antigen (HLA) antibody at Week 20 (which is Study Week 24) post treatment initiation,
    2. 50% or greater reduction in the mean fluorescence intensity (MFI) of at least three HLA antibodies at Week 20 (which is Study Week 24) after starting treatment, and/or
    3. Kidney transplant with a previously incompatible donor within 20 weeks after starting treatment without graft loss due to acute antibody mediated rejection occurring within the first four weeks post-transplant and caused by an anamnestic response.

    Measured: Baseline (Visit 0) to Week 20 post treatment initiation

  4. Proportion of subjects who meet any one of the pre-specified events detailed in the outcome description: from Baseline to Week 24 post treatment initiation - Cohort 2

    Proportion of subjects who meet any one of the following compared to Baseline (Visit 0):

    1. Elimination of one human leukocyte antigen (HLA) antibody at Week 24 (which is Study Week 28) post treatment initiation,
    2. 50% or greater reduction in the mean fluorescence intensity (MFI) of at least three HLA antibodies at Week 24 (which is Study Week 28) after starting treatment, and/or
    3. Kidney transplant with a previously incompatible donor within 52 weeks after starting treatment without graft loss due to acute antibody mediated rejection occurring within the first four weeks post-transplant and caused by an anamnestic response.

    Measured: Baseline (Visit 0) to Week 24 post treatment initiation

Secondary outcomes (18)

  1. Proportion of subjects transplanted with a DSA-negative donor to whom DSA was previously positive, within 52 weeks after starting treatment

    Clinical outcome measure.

    Subjects may receive a kidney transplant while in the study, either from a living or deceased donor to whom they were previously compatible, or from a previously incompatible donor in case there is a significant reduction in HLA antibody.

    Measured: Within 52 weeks post treatment initiation

  2. Proportion of subjects with biopsy-proven acute or chronic antibody mediated rejection (AMR) within 52 weeks post-transplant in subjects who undergo a kidney transplant

    Clinical outcome measure.

    Antibody mediated rejection (AMR) is an important cause of graft loss after organ transplantation and is caused by anti-donor-specific antibodies, especially anti- human leukocyte antigen (HLA) antibodies.

    Measured: Within 52 weeks post-transplant

  3. Number of biopsy-proven acute or chronic AMR events within 52 weeks post-transplant in subjects who undergo a kidney transplant

    Clinical outcome measure.

    Antibody mediated rejection (AMR) is an important cause of graft loss after organ transplantation and is caused by anti-donor-specific antibodies, especially anti- human leukocyte antigen (HLA) antibodies.

    Measured: Within 52 weeks post-transplant

  4. Proportion of subjects with invasive fungal infections, mycobacterial infections or Pneumocystis jirovecii infection within 24 weeks after starting treatment

    A measure of infection-related morbidity.

    Measured: Within 24 weeks post treatment initiation

  5. Proportion of subjects with invasive fungal infections, mycobacterial infections or Pneumocystis jirovecii infection within 52 weeks after starting treatment

    A measure of infection-related morbidity.

    Measured: Within 52 weeks post treatment initiation

  6. Number of invasive fungal infections, mycobacterial infections, or Pneumocystis jirovecii infection events within 24 weeks after starting treatment

    A measure of infection-related morbidity.

    Measured: Within 24 weeks post treatment initiation

  7. Number of invasive fungal infections, mycobacterial infections, or Pneumocystis jirovecii infection events within 52 weeks after starting treatment

    A measure of infection-related morbidity.

    Measured: Within 52 weeks post treatment initiation

  8. Proportion of subjects with cytomegalovirus (CMV) infection and disease within 24 weeks after starting treatment

    CMV infection confirmed by the presence of detectable CMV in blood by polymerase chain reaction [PCR] diagnostic testing, regardless of whether signs or symptoms are present.

    Measured: Within 24 weeks post treatment initiation

  9. Proportion of subjects with cytomegalovirus (CMV) infection and disease within 52 weeks after starting treatment

    CMV infection confirmed by the presence of detectable CMV in blood by polymerase chain reaction [PCR] diagnostic testing, regardless of whether signs or symptoms are present.

    Measured: Within 52 weeks post treatment initiation

  10. Number of cytomegalovirus (CMV) infection events within 24 weeks after starting treatment

    Measured: Within 24 weeks post treatment initiation

  11. Number of cytomegalovirus (CMV) infection events within 52 weeks after starting treatment

    Measured: Within 52 weeks post treatment initiation

  12. Proportion of subjects with post-transplant lymphoproliferative disorder (PTLD) within 52 weeks post-transplant

    As per diagnosis by local pathologist and treating physician.

    Measured: Within 52 weeks post-transplant

  13. Number of post-transplant lymphoproliferative disorder (PTLD) events within 52 weeks post-transplant

    Measured: Within 52 weeks post-transplant

  14. Proportion of subjects transplanted with a donor to whom donor-specific antibody (DSA) was previously positive and reduced by ≥50% at the time of transplant within 52 weeks after starting treatment

    Measured: Within 52 weeks post-transplant

  15. Mean number of Human Leukocyte Antigen (HLA) antibodies eliminated at 16 weeks compared to Baseline (Cohort 1)

    Mechanistic outcome measure focusing on change in donor specific antibodies (DSA).

    Measured: Baseline (Visit 0), Week 16 post treatment initiation

  16. Mean number of Human Leukocyte Antigen (HLA) antibodies eliminated at 52 weeks compared to Baseline (Cohort 2)

    Mechanistic outcome measure focusing on change in donor specific antibodies (DSA).

    Measured: Baseline (Visit 0), Week 52 post treatment initiation

  17. Mean percentage of Human Leukocyte Antigen (HLA) antibodies eliminated at 16 weeks compared to Baseline (Cohort 1)

    Mechanistic outcome measure focusing on change in donor specific antibodies (DSA).

    Measured: Baseline (Visit 0), Weeks 16, and 52 post treatment initiation

  18. Mean percentage of Human Leukocyte Antigen (HLA) antibodies eliminated at 52 weeks compared to Baseline (Cohort 2)

    Mechanistic outcome measure focusing on change in donor specific antibodies (DSA).

    Measured: Baseline (Visit 0), Weeks 16, and 52 post treatment initiation

Timeline

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

  1. First posted24 Aug 2021
  2. Study start28 Dec 2021
  3. Primary completion5 Aug 2026
  4. Study completionApr 2027 (estimated)

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05017545
Sponsor's protocol ID
DAIT ITN089ST
Other IDs
ITN089ST, NIAID CRMS ID#: 38685
Acronym
ADAPT
Status last verified
Nov 2026
First submitted
17 Aug 2021
Last updated
5 Nov 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: The plan is to share data upon completion of the study in: Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing carfilzomib, belatacept and Bone marrow aspiration in people with Highly Sensitized Prospective Kidney Transplant Recipients, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.

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 36 inclusion and 29 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: under way, not looking for participants, as of the sponsor's last update on 5 Nov 2026. 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 United States. 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

This study is still under way. Results are not available in the source record yet.

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 subjects who do not meet a stopping rule for safety and remain free of all of the following through 20 weeks (Cohort 1) after starting treatment or until receiving a transplant, whichever occurs earlier. (time frame: Up to 26 weeks post treatment initiation). The study lists 4 primary outcomes in all. 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 NCT05017545.

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 5 Nov 2026.

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