TLI- and ATG-Enabled Minimization Protocol in Liver Transplantation (TEMPO-LT)
A Phase 1-2 Prospective Study to Evaluate the Safety and Feasibility of Total Lymphoid Irradiation (TLI) and Anti-Thymocyte Globulin (ATG) in Liver Transplantation Recipients to Induce Immune Tolerance
The unmet medical need in solid organ transplantation is to eliminate the lifelong requirement of powerful immune suppression drug combinations with their attendant side effects, and to prevent immune mediated rejection of the organ transplant. The proposed trial is designed to study if following a 'standard of care' deceased donor liver transplant host conditioning using Total Lymphoid Irradiation (TLI) and Anti-Tthymocyte Globulin (ATG) will result in operational tolerance and ultimately allow for immunosuppression drug minimization or cessation.
It has been hypothesized that the ATG and TLI conditioning regimen post liver transplant will be safe and well tolerated and will result in recipients successfully being withdrawn from immunosuppression within 2 years after liver transplantation. We will test the hypothesis that by using a conditioning regimen of ATG and TLI to induce this operational tolerance will allow immunosuppressive drug minimization and cessation while maintaining normal graft function and without the risk of graft rejection.
Importance of this knowledge:
Operational tolerance occurs spontaneously in a minority of liver transplant recipients; however, predictable and reproducible induction of tolerance remains an unmet need. Building on extensive experience with TLI-based tolerance induction in kidney transplantation at Stanford, this study aims to evaluate whether a non-myeloablative conditioning regimen using TLI and ATG can safely facilitate immunosuppression minimization and withdrawal in liver transplant recipients without the use of donor hematopoietic cell infusion.
Studie Overzicht
Toestand
Conditie
Interventie / Behandeling
Studietype
Inschrijving (Geschat)
Fase
- Fase 2
- Fase 1
Contacten en locaties
Studie Locaties
-
-
California
-
Stanford, California, Verenigde Staten, 94305
- Stanford University
-
Contact:
- Study Team
- Telefoonnummer: 650-736-5138
- E-mail: atahsin2@stanford.edu
-
-
Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
- Volwassen
Accepteert gezonde vrijwilligers
Beschrijving
Inclusion Criteria:
- Undergoing liver transplantation at Stanford University
- No contraindications to Total Lymphoid Irradiation or rabbit antithymocyte globulin (rATG)
Exclusion Criteria:
- Contraindications to Total Lymphoid Irradiation (e.g. pregnancy, bone marrow suppression or disease, autoimmune disease, prior radiation in the field)
- Contraindications to rATG
- Patients with history of hepatocellular carcinoma (HCC) or other malignancies with exception of non melanoma skin cancer in remission Model of End-Stage Liver Disease (MELD) score > 25 Liver transplants with severe reperfusion syndrome (hemodynamic instability requiring 3 or more pressors after reperfusion) Liver transplant with early allograft dysfunction (Orloff criteria) Diagnosis of hepatitis B Diagnosis of hepatitis C, except for patients that have been treated and eradicated of hepatitis C Virtual and/or flow crossmatch positive (MFI added up to 8000 for each DSA with MFI>1000).
Subject has previously received or is receiving another organ for transplant other than liver Subject is currently on dialysis Recipient or donor is HIV positive Subject has received an ABO incompatible donor Subject has received a donor liver greater than 65 years of age Subject has an active infection at the time of transplant Subject will require immunosuppressive agent other than those prescribed in this study Subject is pregnant or lactating Subject is unlikely to comply with the visits scheduled in the protocol, including protocol biopsies Subject has any form of current substance use, psychiatric disorder or condition that may invalidate communication with the Investigators
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: Niet-gerandomiseerd
- Interventioneel model: Parallelle opdracht
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
|---|---|
|
Experimenteel: Anti-thymocyte globulin and Total Lymphoid Irradiation (synchronous tolerance)
Participants undergo a conditioning regimen with Anti-thymocyte globulin of 1.5 mg/kg ATG intravenously over 3 - 4 days immediately after liver transplant surgery and Total Lymphoid Irradiation post liver transplant surgery to induce immune tolerance, which thereby, improves graft engraftment.
|
1.5 mg/kg ATG will be administered intravenously over 3-4 days.
The ATG doses will be completed within 5 days of the liver transplant.
Participants will get 8 doses of TLI over 2 weeks with a total radiation dose of 960 cGy.
|
|
Experimenteel: Anti-thymocyte globulin and Total Lymphoid Irradiation (delayed tolerance)
Participants undergo a conditioning regimen with Anti-thymocyte globulin of 1.5 mg/kg ATG intravenously over 3 - 4 days after a while after liver transplant surgery and Total Lymphoid Irradiation post liver transplant surgery to induce immune tolerance, which thereby, improves graft engraftment.
|
1.5 mg/kg ATG will be administered intravenously over 3-4 days.
The ATG doses will be completed within 5 days of the liver transplant.
Participants will get 8 doses of TLI over 2 weeks with a total radiation dose of 960 cGy.
|
Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
The success rate
Tijdsspanne: After intervention through 18 months and monitored monthly up to 36 months.
|
The success rate is defined as the percentage of participants free from all immunosuppressive drugs by 18 months after the start of the conditioning regimen).
This will be estimated with standard errors by the Kaplan-Meier procedure and the Greenwood formula.
|
After intervention through 18 months and monitored monthly up to 36 months.
|
Medewerkers en onderzoekers
Sponsor
Onderzoekers
- Hoofdonderzoeker: Stephan Busque, MD, MSc, Stanford University
Studie record data
Bestudeer belangrijke data
Studie start (Geschat)
Primaire voltooiing (Geschat)
Studie voltooiing (Geschat)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Werkelijk)
Updates van studierecords
Laatste update geplaatst (Werkelijk)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Aanvullende relevante MeSH-voorwaarden
Andere studie-ID-nummers
- 86730
Plan Individuele Deelnemersgegevens (IPD)
Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?
Informatie over medicijnen en apparaten, studiedocumenten
Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel
Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct
product vervaardigd in en geëxporteerd uit de V.S.
Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .