ACTIVE_NOT_RECRUITING

Daratumumab 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 on waitlist. The purpose of this study is to find out whether two drugs, daratumumab (Darzalex®), 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

A Mechanistically Driven Therapy to Desensitize >98.0% cPRA Patients: Depletion of Plasma Cells With Anti-CD38 and Prevention of B Cell Activation With Costimulation Blockade (ITN090ST)

Quick Facts

Study Start:2021-11-01

Study Completion:2028-04-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT04827979

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 listed with current calculated panel reactive antibodies (cPRA) ≥99.9% or \>98% (with \>5 years of waiting time) awaiting deceased donor transplant 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 TB infection (LTBI) therapy. * Testing should be conducted using either a PPD or interferon-gamma release assay (i.e., QuantiFERON-TB, T-SPOT.TB) * 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 for LTBI must complete appropriate therapy for LTBI ---LTBI treatment regimens should be among those endorsed by the Centers for 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 12 months prior to screening) 7. Negative Hepatitis C antibody test at screening or as documented in medical record, up to 12 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. Female subjects of reproductive potential must have a negative pregnancy test upon study entry 10. All subjects of reproductive potential must agree to use of contraception for the duration of the study 11. Subjects must have current vaccinations or documented immunity to varicella, measles, hepatitis B, pneumococcus, influenza, and zoster (if ≥50 years old) * If subjects require administration of vaccines to meet eligibility requirements, they must wait at least 2 weeks between vaccination and the baseline (Visit 0) visit	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 or non-tuberculous mycobacterial infection 3. Hepatitis B surface antigen or core antibody positive 4. Serious uncontrolled concomitant major organ disease excluding kidney failure 5. Previous non-kidney solid organ or bone marrow transplant 6. Any infection requiring hospitalization and intravenous (IV) antibiotics within 4 weeks of screening or by mouth (PO) antibiotics within 2 weeks 7. Primary or secondary immunodeficiency 8. History of active tuberculosis (TB), even if treated 9. History of positive result for 2019-novel Coronavirus (2019-nCoV) by real-time reverse transcriptase (RT-PCR) 10. Malignancy within the last 5 years except treated basal and squamous cell cancer of the skin or treated in situ cervical cancer 11. History of plasma cell dyscrasia 12. Alcohol, drug, or chemical abuse within 1 year 13. Difficult peripheral venous access 14. Need for uninterrupted anticoagulation 15. Neutropenia (absolute neutrophil count \<1000/uL) or thrombocytopenia (platelet count \<100,000/uL) within 4 weeks prior to study enrollment 16. Women who are currently pregnant or nursing 17. Treatment with any investigational agent within 4 weeks (or 5 half-lives of investigational drug, whichever is longer) of screening 18. Current treatment with other biological drug 19. Immunization with live vaccine within 2 weeks of study baseline (Visit 0) visit 20. 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

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 listed with current calculated panel reactive antibodies (cPRA) ≥99.9% or \>98% (with \>5 years of waiting time) awaiting deceased donor transplant
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 TB infection (LTBI) therapy.
* Testing should be conducted using either a PPD or interferon-gamma release assay (i.e., QuantiFERON-TB, T-SPOT.TB)
* 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 for LTBI must complete appropriate therapy for LTBI ---LTBI treatment regimens should be among those endorsed by the Centers for
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 12 months prior to screening)
7. Negative Hepatitis C antibody test at screening or as documented in medical record, up to 12 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. Female subjects of reproductive potential must have a negative pregnancy test upon study entry
10. All subjects of reproductive potential must agree to use of contraception for the duration of the study
11. Subjects must have current vaccinations or documented immunity to varicella, measles, hepatitis B, pneumococcus, influenza, and zoster (if ≥50 years old)
* If subjects require administration of vaccines to meet eligibility requirements, they must wait at least 2 weeks between vaccination and the baseline (Visit 0) visit

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 or non-tuberculous mycobacterial infection
3. Hepatitis B surface antigen or core antibody positive
4. Serious uncontrolled concomitant major organ disease excluding kidney failure
5. Previous non-kidney solid organ or bone marrow transplant
6. Any infection requiring hospitalization and intravenous (IV) antibiotics within 4 weeks of screening or by mouth (PO) antibiotics within 2 weeks
7. Primary or secondary immunodeficiency
8. History of active tuberculosis (TB), even if treated
9. History of positive result for 2019-novel Coronavirus (2019-nCoV) by real-time reverse transcriptase (RT-PCR)
10. Malignancy within the last 5 years except treated basal and squamous cell cancer of the skin or treated in situ cervical cancer
11. History of plasma cell dyscrasia
12. Alcohol, drug, or chemical abuse within 1 year
13. Difficult peripheral venous access
14. Need for uninterrupted anticoagulation
15. Neutropenia (absolute neutrophil count \<1000/uL) or thrombocytopenia (platelet count \<100,000/uL) within 4 weeks prior to study enrollment
16. Women who are currently pregnant or nursing
17. Treatment with any investigational agent within 4 weeks (or 5 half-lives of investigational drug, whichever is longer) of screening
18. Current treatment with other biological drug
19. Immunization with live vaccine within 2 weeks of study baseline (Visit 0) visit
20. 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

Contacts and Locations

Principal Investigator

Flavio G. Vincenti

STUDY_CHAIR

UCSF Kidney Transplant Research

Study Locations (Sites)

University of California at San Francisco Medical Center

San Francisco, California, 94143

United States

Collaborators and Investigators

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

Flavio G. Vincenti, STUDY_CHAIR, UCSF Kidney Transplant Research

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 Date2021-11-01

Study Completion Date2028-04-30

Study Record Updates

Study Start Date2021-11-01

Study Completion Date2028-04-30

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