RECRUITING

Expanding Liver Transplant Immunosuppression Minimization Via Everolimus

Conditions

Liver Transplant Liver Transplant Everolimus

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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

This is a study to determine the safety, efficacy, and tolerability of taking away the anti-rejection medicine, tacrolimus, in liver transplant recipients in conjunction with everolimus monotherapy to preserve renal function. Two hundred - seventy (270) subjects will be randomized 2:1 into one of two groups between 2-3 months post-transplant. Seventy participants will be placed into an observational group and will remain on their current post-transplant medications. The duration of the study from time of enrollment is 18-20 months.

Official Title

Expanding Liver Transplant Immunosuppression Minimization Via Everolimus (CTOT-43)

Quick Facts

Study Start:2024-09-12

Study Completion:2029-06-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06280950

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

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Subject and/or legal guardian must be able to understand and provide informed consent 2. Adult recipient of first liver transplant alone (de novo) 3. Estimated glomerular filtration rate \>=30 ml/min/1.73m\^2 at enrollment using the CKD-EPI 2021 equation 4. Treatment with tacrolimus therapy, with or without mycophenolic acid derivatives and/or corticosteroids 5. Female subjects of childbearing potential with negative pregnancy test upon study entry 6. All subjects of reproductive potential agreeing to use contraception for the duration of the study 7. Previous vaccination or documented immunity to varicella, measles, hepatitis B, pneumococcus, influenza, zoster (if \>=19 years old), and 2019-nCoV (COVID-19) as outlined in the DAIT Vaccination Guideline	1. Inability or unwillingness of a participant to give written informed consent or comply with study protocol 2. Active unresolved systemic viral, bacterial, fungal, or parasitic infection requiring oral or intravenous anti-infective therapy 3. History of autoimmune liver disease including autoimmune hepatitis, primary sclerosing cholangitis, and/or primary biliary cirrhosis, or other contraindications to drug withdrawal 4. History of non-hepatic autoimmune disease requiring current or future systemic immunosuppressive therapy other than per study protocol 5. History of Hepatic Artery Thrombosis or Portal Vein Thrombosis. 6. Chronic use of systemic glucocorticoids, biological immunomodulatory therapy, or other immunosuppressive agents other than per study protocol 7. History of hepatitis B or C virus infection with detectable viral PCR at enrollment 8. History of prior organ transplantation (liver or other type) 9. History of \>= 2 biopsy-proven acute cellular rejection episodes of any severity, \>=1 moderate to severe rejection episode (histologically defined or requiring lymphodepletion therapy), or \>= 1 antibody- mediated rejection episode 10. Active treatment with any mTOR-inhibitor agent (everolimus, sirolimus) 11. Contraindication to treatment with everolimus (open wound or wound infection; urine protein: creatinine ratio \> 0.5; significant pancytopenia (any of the following: WBC \<1.5 K/uL or ANC \<1000 cells/microL or actively being treated with GCSF; Hb \<8.0; platelet count \<50K); serum triglycerides \> 1000 mg/dL; other per PI) 12. Abnormal liver function tests on study entry: Total Bilirubin (TB)\>1.5 mg/dL and Direct Bilirubin (DB) \>1.0 mg/dL, Alkaline Phosphatase (AP) \>200 U/L, and Alanine Aminotransaminase (ALT)\>60 U/L 13. Pregnant on enrollment or plan to become pregnant during the study period 14. Participation in another clinical trial that would interfere with this study's procedures and intervention: 1. Use of investigational biologic or drug (within 8 weeks of study enrollment) 2. Additional blood collection that would exceed research blood draw limits 3. Any other procedure or intervention, in the investigator's opinion would interfere with this study 15. Received live attenuated vaccine(s) within 2 months of enrollment 16. Current, diagnosed, mental illness or current, diagnosed, 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 or that may impact the quality or interpretation of the data obtained from the study 17. 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.

Inclusion Criteria

Exclusion Criteria

1. Subject and/or legal guardian must be able to understand and provide informed consent
2. Adult recipient of first liver transplant alone (de novo)
3. Estimated glomerular filtration rate \>=30 ml/min/1.73m\^2 at enrollment using the CKD-EPI 2021 equation
4. Treatment with tacrolimus therapy, with or without mycophenolic acid derivatives and/or corticosteroids
5. Female subjects of childbearing potential with negative pregnancy test upon study entry
6. All subjects of reproductive potential agreeing to use contraception for the duration of the study
7. Previous vaccination or documented immunity to varicella, measles, hepatitis B, pneumococcus, influenza, zoster (if \>=19 years old), and 2019-nCoV (COVID-19) as outlined in the DAIT Vaccination Guideline

1. Inability or unwillingness of a participant to give written informed consent or comply with study protocol
2. Active unresolved systemic viral, bacterial, fungal, or parasitic infection requiring oral or intravenous anti-infective therapy
3. History of autoimmune liver disease including autoimmune hepatitis, primary sclerosing cholangitis, and/or primary biliary cirrhosis, or other contraindications to drug withdrawal
4. History of non-hepatic autoimmune disease requiring current or future systemic immunosuppressive therapy other than per study protocol
5. History of Hepatic Artery Thrombosis or Portal Vein Thrombosis.
6. Chronic use of systemic glucocorticoids, biological immunomodulatory therapy, or other immunosuppressive agents other than per study protocol
7. History of hepatitis B or C virus infection with detectable viral PCR at enrollment
8. History of prior organ transplantation (liver or other type)
9. History of \>= 2 biopsy-proven acute cellular rejection episodes of any severity, \>=1 moderate to severe rejection episode (histologically defined or requiring lymphodepletion therapy), or \>= 1 antibody- mediated rejection episode
10. Active treatment with any mTOR-inhibitor agent (everolimus, sirolimus)
11. Contraindication to treatment with everolimus (open wound or wound infection; urine protein: creatinine ratio \> 0.5; significant pancytopenia (any of the following: WBC \<1.5 K/uL or ANC \<1000 cells/microL or actively being treated with GCSF; Hb \<8.0; platelet count \<50K); serum triglycerides \> 1000 mg/dL; other per PI)
12. Abnormal liver function tests on study entry: Total Bilirubin (TB)\>1.5 mg/dL and Direct Bilirubin (DB) \>1.0 mg/dL, Alkaline Phosphatase (AP) \>200 U/L, and Alanine Aminotransaminase (ALT)\>60 U/L
13. Pregnant on enrollment or plan to become pregnant during the study period
14. Participation in another clinical trial that would interfere with this study's procedures and intervention:
1. Use of investigational biologic or drug (within 8 weeks of study enrollment)
2. Additional blood collection that would exceed research blood draw limits
3. Any other procedure or intervention, in the investigator's opinion would interfere with this study
15. Received live attenuated vaccine(s) within 2 months of enrollment
16. Current, diagnosed, mental illness or current, diagnosed, 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 or that may impact the quality or interpretation of the data obtained from the study
17. 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.

Contacts and Locations

Study Contact

Merideth Brown Shifflett, MS

CONTACT

240-627-3483

brownmeri@nih.gov

Tracia Debnam, MS

CONTACT

301-761-7414

Tracia.debnam@nih.gov

Principal Investigator

Josh Levitsky, MD, MS

PRINCIPAL_INVESTIGATOR

Northwestern University Feinberg School of Medicine: Transplantation

Study Locations (Sites)

Mayo Clinic Hospital Arizona (Site #: 71144)

Phoenix, Arizona, 85054

United States

University of California, San Francisco (Site #: 71108)

San Francisco, California, 94143

United States

Northwestern University (Site #: 71110)

Chicago, Illinois, 60611

United States

Icahn School of Medicine at Mount Sinai (Site #: 71115)

New York, New York, 10029

United States

Duke University Medical Center (Site #: 71139)

Durham, North Carolina, 27710

United States

University of Pennsylvania (Site #: 71111)

Philadelphia, Pennsylvania, 19104

United States

University of Pittsburgh Medical Center (Site #: 71170)

Pittsburgh, Pennsylvania, 15260

United States

Baylor Medical Center (Site #: 71153)

Dallas, Texas, 75246

United States

Collaborators and Investigators

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

Josh Levitsky, MD, MS, PRINCIPAL_INVESTIGATOR, Northwestern University Feinberg School of Medicine: Transplantation

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 Date2024-09-12

Study Completion Date2029-06-01

Study Record Updates

Study Start Date2024-09-12

Study Completion Date2029-06-01

Terms related to this study

Keywords Provided by Researchers

Liver
Transplant
Everolimus

Additional Relevant MeSH Terms

Liver Transplant