RECRUITING

Carfilzomib and Belatacept for Desensitization

Conditions

Highly Sensitized Prospective Kidney Transplant Recipients calculated panel reactive antibodies (cPRA)desensitization therapy human leukocyte antigen (HLA) desensitization

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2021-12-28

Study Completion:2028-02-28

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05017545

Participation Criteria

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

Ages Eligible for Study:18 Years to 65 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
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. 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. 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)	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. 1. There are no exclusion criteria for living donors.

Inclusion Criteria

Exclusion Criteria

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.
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.
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)

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.
1. There are no exclusion criteria for living donors.

Contacts and Locations

Principal Investigator

Stuart J. Knechtle, MD

STUDY_CHAIR

Duke Department of Surgery, Duke University School of Medicine

Annette M. Jackson, PhD

STUDY_CHAIR

Duke Department of Surgery, Duke University School of Medicine

Study Locations (Sites)

Duke Transplant Center, Duke University Medical Center

Durham, North Carolina, 27710

United States

Collaborators and Investigators

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

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

Study Record Dates

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

Study Registration Dates

Study Start Date2021-12-28

Study Completion Date2028-02-28

Study Record Updates

Study Start Date2021-12-28

Study Completion Date2028-02-28

Terms related to this study

Keywords Provided by Researchers

calculated panel reactive antibodies (cPRA)
desensitization therapy
human leukocyte antigen (HLA) desensitization

Additional Relevant MeSH Terms

Highly Sensitized Prospective Kidney Transplant Recipients