Daratumumab and Belatacept for Desensitization

  • STATUS
    Recruiting
  • End date
    Jun 2, 2023
  • participants needed
    15
  • sponsor
    National Institute of Allergy and Infectious Diseases (NIAID)
Updated on 2 December 2021

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 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.

Description

This study will enroll 15 eligible adult participants 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.

The study treatment is comprised of two drugs, Darzalex (daratumumab) and Nulojix (belatacept). Daratumumab is licensed for treatment of multiple myeloma and belatacept is licensed for prevention of rejection after kidney transplant. Eligible participants will receive infusions of daratumumab and belatacept over a 10-week period. An interim safety and efficacy analysis will occur after the first 5 participants have received study treatment. All subjects will undergo HLA antibody assessments and bone marrow aspiration prior to and after completion of treatment and receive 42 weeks of follow up after completing treatment. Participants who prematurely discontinue study therapy will receive follow up through 56 weeks after their baseline visit. Subjects who receive a kidney transplant while in the study will receive standard of care immunosuppression and undergo additional 52 weeks of follow up. Living donors will participate for one study visit to provide blood collection.

Details
Condition Highly Sensitized Prospective Kidney Transplant Recipients
Treatment Belatacept, bone marrow aspiration, Daratumumab
Clinical Study IdentifierNCT04827979
SponsorNational Institute of Allergy and Infectious Diseases (NIAID)
Last Modified on2 December 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

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 hemodialysis
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
\--Note: Those with cPRA >98% with human leukocyte antigen (HLA)-incompatible
approved living donor who have not received a transplant after 1 year in a
paired kidney exchange program are also eligible
\. 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 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
Disease Control and Prevention (CDC), Division of TB Elimination, 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 12 months prior to screening)
\. Negative Hepatitis C antibody test at screening or as documented in
medical record, up to 12 months prior to screening
\--If there is a history of treated hepatitis C or there is a suspected false
positive hepatitis C virus (HCV) antibody test, then documentation of two
consecutive negative HCV quantitative ribonucleic acid (RNA) Polymerase chain
reaction (PCR) tests separated by at least 6 months is required
\. Negative result for 2019-novel Coronavirus (2019-nCoV) by real-time
reverse transcriptase (RT-PCR)
\. Female subjects of reproductive potential must have a negative pregnancy
test upon study entry
\. All subjects of reproductive potential must agree to use of contraception
for the duration of the study
\. 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

Exclusion Criteria

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