Advancing Transplantation Outcomes in Children

What is the Purpose of this Study?

This study focuses on pediatric patients who are receiving a kidney transplant at Cedars-Sinai. The purpose of the study is to determine whether an experimental combination of immunosuppressive drugs: belatacept and sirolimus, preserves kidney function and prevents development of antibodies that can lead to a severe form of rejection. Patients who receive kidney transplants take anti-rejection drugs every day to prevent the body from rejecting the new kidney. Rejection occurs when the new kidney triggers the body’s defense (immune) system and special cells and/or antibodies are sent out to destroy the new kidney. At the time of transplant, participants will be randomly assigned 1 of 2 groups. The groups will receive different anti-rejection medications. Group 1 (Novel Immunosuppression Group) will receive belatacept and sirolimus. Group 2 (Standard Immunosuppression Group) will receive tacrolimus and mycophenolate mofetil.

Eligibility

1. Participant and/or parent/guardian must be able to understand and provide informed consent
2. Male or female, 13-20 years of age at time of enrollment
3. Candidate for primary renal allograft from a deceased donor
4. EBV IgG seropositive, defined as evidence of acquired immunity shown by the presence of IgG antibodies to viral capsid antigen (VCA) and EBV nuclear antigen (EBNA)

Inclusion Criteria:

1. Participant and/or parent/guardian must be able to understand and provide informed consent
2. Male or female, 13-20 years of age at time of enrollment
3. Candidate for primary renal allograft from a deceased donor
4. EBV IgG seropositive, defined as evidence of acquired immunity shown by the presence of IgG antibodies to viral capsid antigen (VCA) and EBV nuclear antigen (EBNA)
5. EBV VCA IgM seronegative
6. If a female participant of childbearing potential, a negative pregnancy test within 48 hours of enrollment
7. If participant has reproductive potential, agrees to use Food and Drug Administration (FDA) approved methods of birth control for the duration of the study
8. Negative test result for latent tuberculosis infection by tuberculosis skin test (purified protein derivative \[PPD\]) or Tuberculosis (TB) blood test (interferon gamma release assay \[IGRA\] i.e., QuantiFERON, T- SPOT.TB) within 12 months
9. In the absence of contraindication, vaccinations must be up to date per the Centers for Disease Control and Prevention (CDC) Guidelines and Division of Allergy, Immunology, and Transplantation (DAIT) Guidance for Patients in Transplant Trials

Exclusion Criteria:

1. Inability or unwillingness to comply with study protocol
2. Active infection requiring treatment, or viremia
3. History of malignancy
4. Receipt of any licensed or investigational live attenuated vaccine(s) within 4 weeks of enrollment
5. Prior history of organ transplantation
6. Active systemic autoimmune disease at time of enrollment
7. Idiopathic Focal Segmental Glomerulosclerosis (FSGS), Membranoproliferative Glomerulonephritis (MPGN), C3 glomerulopathy, or atypical Hemolytic Uremic Syndrome (HUS) suspected at risk for recurrence
8. Use of immunosuppressants, biologics (including IVIG), chronic corticosteroids or investigational drug(s) within 8 weeks of enrollment
9. Known bleeding disorder
10. Sustained platelet count \< 75,000 cells/microliters within 3 months of enrollment
11. History of inherited hypercoagulability requiring therapy more than aspirin
12. Clinically significant unrepaired congenital heart disease causing hemodynamic compromise
13. Uncontrolled diagnosed psychiatric disorder or self-reported drug or alcohol abuse that, in the opinion of the investigator, would interfere with the participant's ability to comply with study requirements
14. Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study
Individuals who meet all of the following criteria are eligible for randomization.
1. EBV VCA IgG and EBV EBNA IgG seropositive, confirmed between enrollment and time of transplant
2. EBV VCA IgM seronegative, confirmed between enrollment and time of transplant
Individuals who meet any of these criteria are not eligible for randomization.
1. Sustained WBC \<1500 or \>20,000 per microliter within 3 months of randomization
2. Sustained liver function tests (AST and/or ALT) \> 2x normal within 3 months of randomization
3. Active systemic autoimmune disease at time of transplant
4. Known bleeding disorder
5. Sustained platelet count \< 75,000 cells/microliters within 3 months of enrollment
6. Current (within 30 days) or historical anti-HLA antibody to the donor prior to randomization
7. Recent recipient of any licensed or investigational live attenuated vaccine(s) within 4 weeks of randomization
8. Panel Reactive Antibody (cPRA) greater than 80 percent
9. If a female participant of childbearing potential, a positive pregnancy test within 48 hours of randomization (all female participants of childbearing potential must complete a pregnancy test within 48 hours of randomization)
10. Treatment with immunosuppressants, including biologics (including IVIG), within 8 weeks of randomization

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Where can I participate?

Beverly

More about this Clinical Trial

What is the full name of this clinical trial?

CTOT-41: ADVANCING TRANSPLANTATION OUTCOMES IN CHILDREN

Study Details

Disease Type/Condition

Other

Principal Investigator

Puliyanda, Dechu

Co-Investigators

Helen Pizzo

Age Group

Children

Phase

IRB Number

STUDY00003041

ClinicalTrials.gov ID

NCT06055608

Key Eligibility

ClinicalTrials.gov

How do I learn more about this study?

clinicaltrials@cshs.org