RECRUITING

Cytomegalovirus (CMV) Vaccine in Orthotopic Liver Transplant Candidates

Conditions

Liver Transplant Cytomegalovirus Vaccine Orthotopic Liver Transplant

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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 multi-center clinical trial in Cytomegalovirus (CMV) seronegative prospective liver transplant recipients to determine the efficacy of two doses of Cytomegalovirus-Modified Vaccinia Ankara (CMV-MVA) Triplex CMV vaccine pre-transplant. The primary objective is to assess the effect of pre-transplant (Tx) Triplex vaccination on duration of CMV antiviral therapy (AVT) within the first 100 days post-Tx in CMV seropositive donor (D+) and seronegative (R-) (D+R-) liver transplant recipients (LTxRs). A protocol-mandated preemptive therapy (PET) will be used for CMV disease prevention in D+R- LTxRs.

Official Title

Cytomegalovirus (CMV) Vaccine in Orthotopic Liver Transplant Candidates (CTOT-44)

Quick Facts

Study Start:2024-03-05

Study Completion:2028-02-28

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06075745

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 must be able to understand and provide informed consent 2. Negative for antibody to Cytomegalovirus (CMV) as assessed in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory within 6 months of enrollment, and no history of prior positive CMV serology (IgG antibody) 3. Negative screening test for human immunodeficiency virus (HIV) and no clinical suspicion of HIV infection 4. Listed for a first living or deceased donor liver transplant 5. Anticipated to receive a liver transplant within 1-12 months 6. For individuals of reproductive potential, a negative serum or urine pregnancy test within 72 hours prior to enrollment. NOTE: Individuals of reproductive potential are defined as individuals who have reached menarche and who have not been post-menopausal for at least 12 consecutive months with follicle-stimulating hormone (FSH) \>=40 IU/mL or 24 consecutive months if an FSH is not available, i.e., who have had menses within the preceding 24 months, and have not undergone a sterilization procedure (e.g., hysterectomy, bilateral oophorectomy, or salpingectomy) 7. Participants who are able to impregnate or become pregnant (i.e., of reproductive potential) and are participating in sexual activity that could lead to pregnancy must agree to practice contraception/birth control (hormonal or barrier method) or agree to not participate in a conception process (e.g., active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization) for at least 1 month following the last vaccine/placebo dose. For acceptable contraception methods that are more than 80 percent effective, see Food and Drug Administration (FDA) Office of Women's Health (http://www.fda.gov/birthcontrol) 8. The most recent platelet count within 3 months prior to enrollment by any laboratory with CLIA certification or equivalent of \>= 20,000 cells/mm\^3 prior to enrollment, and in the opinion of the investigator, has not decreased \< 20,000 cells/mm\^3 at time of IP administration. 1. Most recent platelet count \>= 20,000 cells/mm\^3 and in the opinion of the investigator, has not decreased \< 20,000 cells/mm\^3 since last result. 2. For women of reproductive potential as defined previously, a negative serum or urine pregnancy test (performed within 72 hours)	1. Women who are breastfeeding or planning to breastfeed 2. Prior Cytomegalovirus (CMV) vaccination 3. Receipt of immunoglobulin or CMV-specific immunoglobulin within the last 3 months (this includes coronavirus disease (COVID) convalescent plasma) 4. Currently enrolled in another interventional study that, in the investigator's opinion, could affect the evaluation of safety and/or vaccine effect outcomes 5. Prior (ever) receipt of a stem cell transplant (Peripheral blood stem cell (PBSC), marrow, cord blood, etc.) 6. Receipt of immunosuppression: 1. Systemic Chemotherapy or immunotherapy for cancer in the last 3 months (localized therapy for hepatocellular carcinoma \[HCC\] such as chemoembolization, Y-90 are not considered "systemic chemotherapy" and are not excluded) 2. Systemic immunosuppressive agents (e.g. cyclophosphamide, methotrexate, mycophenolate, azathioprine, calcineurin inhibitors, mTOR inhibitors, TNF-alpha inhibitors) and/or combination immunosuppressive drugs for any autoimmune or other conditions in the last 3 months, except corticosteroids as below 7. Averaged daily corticosteroid therapy at a dose \>=20 mg of prednisone equivalent in the last 28 days prior to randomization 8. Receipt of T- or B-cell depleting agents (e.g., ATG, Alemtuzumab, Rituximab) within the last 6-months prior to randomization 9. Transplant status 1A or in the opinion of the investigator is likely to receive a transplant within the next 2 months 10. At the time of randomization, either listed for, or, in the opinion of the investigator, likely to receive any non-liver organ transplant 11. Receipt of or planned administration of: 1. Live, attenuated vaccine within 14 days of study agent 2. Subunit or inactivated vaccine within 14 days of study agent 12. Known allergy to any component of the study agent 13. 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 1. Anaphylaxis or other severe reaction (Grade 4) considered definitely or probably attributable to dose 1 2. Receipt of liver transplant prior to dose 2 3. The participant must not have any severe acute illness or other factor, that, in the opinion of the investigator, requires postponement of dose 2 because of safety concerns. The participant can be re-evaluated for eligibility throughout the window of eligibility for the dose 2, once the illness or other factor has improved or resolved

Inclusion Criteria

Exclusion Criteria

1. Subject must be able to understand and provide informed consent
2. Negative for antibody to Cytomegalovirus (CMV) as assessed in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory within 6 months of enrollment, and no history of prior positive CMV serology (IgG antibody)
3. Negative screening test for human immunodeficiency virus (HIV) and no clinical suspicion of HIV infection
4. Listed for a first living or deceased donor liver transplant
5. Anticipated to receive a liver transplant within 1-12 months
6. For individuals of reproductive potential, a negative serum or urine pregnancy test within 72 hours prior to enrollment. NOTE: Individuals of reproductive potential are defined as individuals who have reached menarche and who have not been post-menopausal for at least 12 consecutive months with follicle-stimulating hormone (FSH) \>=40 IU/mL or 24 consecutive months if an FSH is not available, i.e., who have had menses within the preceding 24 months, and have not undergone a sterilization procedure (e.g., hysterectomy, bilateral oophorectomy, or salpingectomy)
7. Participants who are able to impregnate or become pregnant (i.e., of reproductive potential) and are participating in sexual activity that could lead to pregnancy must agree to practice contraception/birth control (hormonal or barrier method) or agree to not participate in a conception process (e.g., active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization) for at least 1 month following the last vaccine/placebo dose. For acceptable contraception methods that are more than 80 percent effective, see Food and Drug Administration (FDA) Office of Women's Health (http://www.fda.gov/birthcontrol)
8. The most recent platelet count within 3 months prior to enrollment by any laboratory with CLIA certification or equivalent of \>= 20,000 cells/mm\^3 prior to enrollment, and in the opinion of the investigator, has not decreased \< 20,000 cells/mm\^3 at time of IP administration.
1. Most recent platelet count \>= 20,000 cells/mm\^3 and in the opinion of the investigator, has not decreased \< 20,000 cells/mm\^3 since last result.
2. For women of reproductive potential as defined previously, a negative serum or urine pregnancy test (performed within 72 hours)

1. Women who are breastfeeding or planning to breastfeed
2. Prior Cytomegalovirus (CMV) vaccination
3. Receipt of immunoglobulin or CMV-specific immunoglobulin within the last 3 months (this includes coronavirus disease (COVID) convalescent plasma)
4. Currently enrolled in another interventional study that, in the investigator's opinion, could affect the evaluation of safety and/or vaccine effect outcomes
5. Prior (ever) receipt of a stem cell transplant (Peripheral blood stem cell (PBSC), marrow, cord blood, etc.)
6. Receipt of immunosuppression:
1. Systemic Chemotherapy or immunotherapy for cancer in the last 3 months (localized therapy for hepatocellular carcinoma \[HCC\] such as chemoembolization, Y-90 are not considered "systemic chemotherapy" and are not excluded)
2. Systemic immunosuppressive agents (e.g. cyclophosphamide, methotrexate, mycophenolate, azathioprine, calcineurin inhibitors, mTOR inhibitors, TNF-alpha inhibitors) and/or combination immunosuppressive drugs for any autoimmune or other conditions in the last 3 months, except corticosteroids as below
7. Averaged daily corticosteroid therapy at a dose \>=20 mg of prednisone equivalent in the last 28 days prior to randomization
8. Receipt of T- or B-cell depleting agents (e.g., ATG, Alemtuzumab, Rituximab) within the last 6-months prior to randomization
9. Transplant status 1A or in the opinion of the investigator is likely to receive a transplant within the next 2 months
10. At the time of randomization, either listed for, or, in the opinion of the investigator, likely to receive any non-liver organ transplant
11. Receipt of or planned administration of:
1. Live, attenuated vaccine within 14 days of study agent
2. Subunit or inactivated vaccine within 14 days of study agent
12. Known allergy to any component of the study agent
13. 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
1. Anaphylaxis or other severe reaction (Grade 4) considered definitely or probably attributable to dose 1
2. Receipt of liver transplant prior to dose 2
3. The participant must not have any severe acute illness or other factor, that, in the opinion of the investigator, requires postponement of dose 2 because of safety concerns. The participant can be re-evaluated for eligibility throughout the window of eligibility for the dose 2, once the illness or other factor has improved or resolved

Contacts and Locations

Principal Investigator

Ajit P Limaye, MD

STUDY_CHAIR

University of California, San Francisco: Transplantation

Cindy Fisher, M.D.

STUDY_CHAIR

University of Washington Medical Center: Transplantation

Study Locations (Sites)

University of Alabama at Birmingham, School of Medicine

Birmingham, Alabama, 35233

United States

University of California, San Diego School of Medicine

La Jolla, California, 92093

United States

Stanford University

Redwood City, California, 94063-3126

United States

University of California, San Francisco

San Francisco, California, 94143-0000

United States

University of Miami, Jackson Memorial Hospital

Miami, Florida, 33136-1003

United States

Emory University Hospital

Atlanta, Georgia, 30322-0000

United States

Northwestern University, Feinberg School of Medicine

Chicago, Illinois, 60611-0000

United States

Johns Hopkins University School of Medicine

Baltimore, Maryland, 21205-0000

United States

University of Michigan Medical Center

Ann Arbor, Michigan, 48109-1274

United States

Mayo Clinic, Rochester - College of Medicine and Science

Rochester, Minnesota, 55905-0001

United States

University of Nebraska Medical Center

Omaha, Nebraska, 68198-7835

United States

Duke University School of Medicine

Durham, North Carolina, 27710-1000

United States

Oregon Health & Sciences University

Portland, Oregon, 97239-3098

United States

University of Pennsylvania School of Medicine

Philadelphia, Pennsylvania, 19104-5127

United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213-0000

United States

Vanderbilt University School of Medicine

Nashville, Tennessee, 37232-0011

United States

University of Texas Southwestern Medical Center

Dallas, Texas, 75390-0000

United States

University of Washington Medical Center: Transplantation

Seattle, Washington, 98195

United States

Collaborators and Investigators

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

Ajit P Limaye, MD, STUDY_CHAIR, University of California, San Francisco: Transplantation
Cindy Fisher, M.D., STUDY_CHAIR, University of Washington Medical Center: 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 Date2024-03-05

Study Completion Date2028-02-28

Study Record Updates

Study Start Date2024-03-05

Study Completion Date2028-02-28

Terms related to this study

Keywords Provided by Researchers

Cytomegalovirus
Vaccine
Orthotopic Liver Transplant

Additional Relevant MeSH Terms

Liver Transplant