Multiple Myeloma Clinical Trial
Carfilzomib and Belatacept for Desensitization
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.
This study will enroll 15 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 will be enrolled in two consecutive Cohorts of 5 and 10 patients respectively. 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 undergo an additional 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.
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
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 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- polymerase chain reaction (RT-PCR)
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 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
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
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
History of positive result for 2019-novel Coronavirus (2019-nCoV) by real-time reverse transcriptase reverse transcriptase-polymerase chain reaction (RT-PCR)
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
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.
Exclusion Criteria for Living Donors:
1. There are no exclusion criteria for living donors.
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There is 1 Location for this study
Durham North Carolina, 27710, United States More Info
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