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Carfilzomib och Belatacept för desensibilisering (ADAPT)

2 november 2026 uppdaterad av: National Institute of Allergy and Infectious Diseases (NIAID)

Mätning av effekten av karfilzomib och belatacept på allogen desensibilisering hos potentiella njurtransplanterade mottagare (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.

Studieöversikt

Status

Aktiv, inte rekryterande

Betingelser

Intervention / Behandling

Detaljerad beskrivning

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.

Studietyp

Interventionell

Inskrivning (Faktisk)

21

Fas

  • Fas 2
  • Fas 1

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studieorter

  • Förenta staterna
    • North Carolina
      • Durham, North Carolina, Förenta staterna, 27710
        • Duke Transplant Center, Duke University Medical Center

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

18 år till 65 år (Vuxen, Äldre vuxen)

Tar emot friska volontärer

Nej

Kön som är behöriga för studier

Allt

Beskrivning

Inclusion Criteria:

Individuals who meet all of the following criteria are eligible for enrollment as study subjects-

  1. Subject must be able to understand and provide informed consent

  2. End stage renal disease (ESRD) on dialysis

  3. 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
    • 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

  4. Evidence of established immunity to Epstein-Barr virus (EBV) as demonstrated by serologic testing

  5. 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

  6. 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)

  7. 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.

  8. 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.

  9. 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

  10. Female subjects of reproductive potential must have a negative pregnancy test upon study entry

  11. All subjects of reproductive potential must agree to use contraception for the duration of the study

  12. 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-

  1. Able to understand and provide informed consent for research
  2. Meets United Network for Organ Sharing (UNOS) requirements for kidney organ donation

Exclusion Criteria:

Individuals who meet any of these criteria are not eligible for enrollment as study subjects-

  1. Inability or unwillingness of a subject to give written informed consent or comply with study protocol

  2. Known active current or history of invasive fungal infection, non-tuberculous mycobacterial infection

  3. Hepatitis B surface antigen or core antibody positive

  4. Serious uncontrolled concomitant major organ disease, excluding kidney failure

  5. Chronic respiratory failure

  6. Uncontrolled systemic hypertension

  7. Previous non-kidney solid organ transplant or bone marrow transplant

  8. Any infection requiring hospitalization and intravenous (IV) therapy within 4 weeks of screening or oral therapy within 2 weeks of screening

  9. Primary or secondary immunodeficiency

  10. History of thromboembolism (except thrombosis of dialysis vascular access site)

  11. Subjects with myocardial infarction within 12 months of screening or cardiac dysrhythmias uncontrolled by medications

  12. History of plasma cell dyscrasia

  13. Known bleeding diathesis or coagulation abnormality

  14. History of active tuberculosis (TB) (even if treated)

  15. Malignancy within the last 5 years except treated basal and squamous cell cancer of the skin or treated cervical cancer in situ

  16. Women who are currently pregnant or nursing

  17. Alcohol, drug, or chemical abuse within 1 year

  18. Treatment with any investigational agent within 4 weeks (or 5 half-lives of investigational drug, whichever is longer) of screening

  19. 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.

  20. Current treatment with any medication which increases the risk of thromboembolic events including oral contraceptives

  21. Currently smoking tobacco

  22. Neutropenia (absolute neutrophil count <1000/microliter) or thrombocytopenia (platelet count <100,000/microliter) within 4 weeks prior to screening

  23. Alanine Aminotransferase (ALT) or aspartate aminotransferase (AST) ≥3 times upper limit of normal (ULN) or total bilirubin ≥ 2 times ULN

  24. 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.

Exclusion Criteria for Living Donors:

1. There are no exclusion criteria for living donors.

Studieplan

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Behandling
  • Tilldelning: Icke-randomiserad
  • Interventionsmodell: Sekventiell tilldelning
  • Maskning: Ingen (Open Label)

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Experimentell: Cohort 1

The 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.
Biologisk: carfilzomib

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.

Andra namn:
  • Kyprolis®
Biologisk: belatacept

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.

Andra namn:
  • Nulojix®
Procedur: Bone marrow aspiration

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.
Experimentell: Cohort 2

The 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.
Biologisk: carfilzomib

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.

Andra namn:
  • Kyprolis®
Biologisk: belatacept

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.

Andra namn:
  • Nulojix®
Procedur: Bone marrow aspiration

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.

Vad mäter studien?

Primära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
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.
Tidsram: Up to 26 weeks post treatment initiation

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).
Up to 26 weeks post treatment initiation
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.
Tidsram: Up to 24 weeks post treatment initiation

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).
Up to 24 weeks post treatment initiation
Proportion of subjects who achieve any one of the following compared to Baseline - Cohort 1
Tidsram: Baseline (Visit 0) to Week 20 post treatment initiation

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.
Baseline (Visit 0) to Week 20 post treatment initiation
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
Tidsram: Baseline (Visit 0) to Week 24 post treatment initiation

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.
Baseline (Visit 0) to Week 24 post treatment initiation

Sekundära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Antalet cytomegalovirus (CMV)-infektionshändelser inom 24 veckor efter behandlingsstart
Tidsram: Inom 24 veckor efter behandlingsstart
Inom 24 veckor efter behandlingsstart
Antal händelser av cytomegalovirus (CMV) infektion inom 52 veckor efter behandlingsstart
Tidsram: Inom 52 veckor efter behandlingsstart
Inom 52 veckor efter behandlingsstart
Antal posttransplantatoriska lymfoproliferativa störningar (PTLD) inom 52 veckor efter transplantation
Tidsram: Inom 52 veckor efter transplantation
Inom 52 veckor efter transplantation
Andel patienter som transplanterats med en donor till vilken donorspecifik antikropp (DSA) tidigare varit positiv och minskat med ≥50% vid transplantationstillfället inom 52 veckor efter behandlingsstart
Tidsram: Inom 52 veckor efter transplantation
Inom 52 veckor efter transplantation
Proportion of subjects transplanted with a DSA-negative donor to whom DSA was previously positive, within 52 weeks after starting treatment
Tidsram: Within 52 weeks post treatment initiation

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.
Within 52 weeks post treatment initiation
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
Tidsram: Within 52 weeks post-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.
Within 52 weeks post-transplant
Number of biopsy-proven acute or chronic AMR events within 52 weeks post-transplant in subjects who undergo a kidney transplant
Tidsram: Within 52 weeks post-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.
Within 52 weeks post-transplant
Proportion of subjects with invasive fungal infections, mycobacterial infections or Pneumocystis jirovecii infection within 24 weeks after starting treatment
Tidsram: Within 24 weeks post treatment initiation

A measure of infection-related morbidity.
Within 24 weeks post treatment initiation
Proportion of subjects with invasive fungal infections, mycobacterial infections or Pneumocystis jirovecii infection within 52 weeks after starting treatment
Tidsram: Within 52 weeks post treatment initiation

A measure of infection-related morbidity.
Within 52 weeks post treatment initiation
Number of invasive fungal infections, mycobacterial infections, or Pneumocystis jirovecii infection events within 24 weeks after starting treatment
Tidsram: Within 24 weeks post treatment initiation

A measure of infection-related morbidity.
Within 24 weeks post treatment initiation
Number of invasive fungal infections, mycobacterial infections, or Pneumocystis jirovecii infection events within 52 weeks after starting treatment
Tidsram: Within 52 weeks post treatment initiation

A measure of infection-related morbidity.
Within 52 weeks post treatment initiation
Proportion of subjects with cytomegalovirus (CMV) infection and disease within 24 weeks after starting treatment
Tidsram: Within 24 weeks post treatment initiation

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.
Within 24 weeks post treatment initiation
Proportion of subjects with cytomegalovirus (CMV) infection and disease within 52 weeks after starting treatment
Tidsram: Within 52 weeks post treatment initiation

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.
Within 52 weeks post treatment initiation
Proportion of subjects with post-transplant lymphoproliferative disorder (PTLD) within 52 weeks post-transplant
Tidsram: Within 52 weeks post-transplant

As per diagnosis by local pathologist and treating physician.
Within 52 weeks post-transplant
Mean number of Human Leukocyte Antigen (HLA) antibodies eliminated at 16 weeks compared to Baseline (Cohort 1)
Tidsram: Baseline (Visit 0), Week 16 post treatment initiation

Mechanistic outcome measure focusing on change in donor specific antibodies (DSA).
Baseline (Visit 0), Week 16 post treatment initiation
Mean number of Human Leukocyte Antigen (HLA) antibodies eliminated at 52 weeks compared to Baseline (Cohort 2)
Tidsram: Baseline (Visit 0), Week 52 post treatment initiation

Mechanistic outcome measure focusing on change in donor specific antibodies (DSA).
Baseline (Visit 0), Week 52 post treatment initiation
Mean percentage of Human Leukocyte Antigen (HLA) antibodies eliminated at 16 weeks compared to Baseline (Cohort 1)
Tidsram: Baseline (Visit 0), Weeks 16, and 52 post treatment initiation

Mechanistic outcome measure focusing on change in donor specific antibodies (DSA).
Baseline (Visit 0), Weeks 16, and 52 post treatment initiation
Mean percentage of Human Leukocyte Antigen (HLA) antibodies eliminated at 52 weeks compared to Baseline (Cohort 2)
Tidsram: Baseline (Visit 0), Weeks 16, and 52 post treatment initiation

Mechanistic outcome measure focusing on change in donor specific antibodies (DSA).
Baseline (Visit 0), Weeks 16, and 52 post treatment initiation

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Samarbetspartners

Bristol-Myers Squibb
Rho Federal Systems Division, Inc.
Immune Tolerance Network (ITN)
PPD Development, LP

Utredare

  • Studiestol: Stuart J. Knechtle, MD, Duke Department of Surgery, Duke University School of Medicine
  • Studiestol: Annette M. Jackson, PhD, Duke Department of Surgery, Duke University School of Medicine

Publikationer och användbara länkar

Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.

Användbara länkar

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart (Faktisk)

28 december 2021

Primärt slutförande (Faktisk)

5 augusti 2026

Avslutad studie (Beräknad)

1 april 2027

Studieregistreringsdatum

Först inskickad

17 augusti 2021

Först inskickad som uppfyllde QC-kriterierna

17 augusti 2021

Första postat (Faktisk)

24 augusti 2021

Uppdateringar av studier

Senaste uppdatering publicerad (Faktisk)

5 november 2026

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

2 november 2026

Senast verifierad

1 november 2026

Mer information

Termer relaterade till denna studie

Nyckelord

Ytterligare relevanta MeSH-villkor

Andra studie-ID-nummer

  • DAIT ITN089ST
  • ITN089ST (Annan identifierare: Immune Tolerance Network (ITN))
  • NIAID CRMS ID#: 38685 (Annan identifierare: DAIT NIAID)

Plan för individuella deltagardata (IPD)

Planerar du att dela individuella deltagardata (IPD)?

JA

IPD-planbeskrivning

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.

Tidsram för IPD-delning

On average, within 24 months after database lock for the trial.

Kriterier för IPD Sharing Access

Open access.

Läkemedels- och apparatinformation, studiedokument

Studerar en amerikansk FDA-reglerad läkemedelsprodukt

Ja

Studerar en amerikansk FDA-reglerad produktprodukt

Nej

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