Donor-Alloantigen-Reactive Regulatory T Cell (darTregs) in Liver Transplantation
NCT ID: NCT02188719
Last Updated: 2020-09-22
Study Results
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View full resultsBasic Information
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TERMINATED
PHASE1
15 participants
INTERVENTIONAL
2014-12-17
2019-06-18
Brief Summary
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* Taking a specific combination of immunosuppressant drugs after liver transplantation
* Receiving one of three different doses of donor-alloantigen-reactive regulatory T cells (darTregs) while taking this specific combination of drugs
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Detailed Description
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Studies show that some of body's cells, called T regulatory cells (Tregs), may play a part in accepting the transplanted liver. The investigators are learning about whether scientists can take Tregs from the blood of a liver transplant recipient and teach them to protect the transplanted liver from rejection. In the laboratory, the recipient Tregs are exposed to cells from the liver donor. Research data suggests that giving these "donor reactive" Tregs back to the transplant recipient might allow a liver transplant recipient to take lower doses of immunosuppressants, or perhaps to stop them altogether, without rejecting the liver.
Conditions
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Study Design
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NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Cohort 1 - Treg-supportive IS only
3 subjects (Cohort 1a) at site 1 (UCSF) and 3 subjects (Cohort 1b) from site 2 (Mayo Rochester) will receive Treg-Supportive immunosuppression (IS) regimen and will not receive Donor-Alloantigen-Reactive T Regulatory Cells (darTregs). Progression from one cohort to the next will depend on the cumulative incidence of sentinel adverse events.
Anti-Thymocyte Globulin - Rabbit
Liver transplantation/Treg-supportive immunosuppression (IS) treatment. Subjects will be given a dose range of 3.0-4.5 mg/kg total, in divided doses of 1.5 mg/kg/day. Subjects who meet eligibility criteria for Thymoglobulin® administration will be given 1.5 mg/kg intravenously (IV) on post-operative day 3, within 72 hours of transplantation. Additional doses of 1.5 mg/kg IV will be administered until CD3 count is \<50/mm\^3 or when the maximal dose of 4.5/mg/kg has been given.
Everolimus
Liver transplantation/Treg-supportive immunosuppression (IS) treatment. Subjects meeting eligibility criteria for Treg-supportive IS regimen will begin EVR no sooner than 30 days after liver transplantation and no later than 44 days after transplantation; with target trough levels of 6-8 μg/L.EVR target trough levels will be further reduced to 4-6 μg/L 24 - 26 weeks after transplantation.
Tacrolimus
Liver transplantation/Treg-supportive immunosuppression (IS) treatment. Between 30 and 44 days following transplant: Subjects who are not eliminated by Exclusion Criteria C1 (Protocol Section 14.3.1) will proceed in the study and receive either TAC-based or EVR- based IS, based on eligibility Criteria C2 (Section 4.3.4 )
* TAC-based IS: reduce TAC trough level to 3-8 μg/dL; continue MMF
* EVR-based IS: reduce TAC trough level to 3-8 μg/dL; EVR target trough level of 6-8 μg/dL; decrease then discontinue MMF
Mycophenolate mofetil
Liver transplantation/Treg-supportive immunosuppression (IS) treatment. 1000 mg total daily dose. MMF will be initiated within 24 hours of transplantation. MMF must be discontinued as soon as target EVR trough levels have been achieved.
Prednisone
Liver transplantation/Treg-supportive immunosuppression (IS) treatment. Solumedrol 500 mg will be given IV on the day of transplantation. Additional Solumedrol will be prescribed according to site-specific standard of care. Oral prednisone should be initiated once oral medication is tolerated.
Anti-Infective Prophylaxis
Intravenous ganciclovir and/or oral Valcyte will be administered for the prophylaxis of cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) for at least six months after liver transplantation.
Blood draws
Blood draws are necessary to carefully and frequently evaluate allograft function after liver transplantation and treatment with Treg-supportive IS as well as after darTreg infusion. Peripheral blood samples will be collected and analyzed per protocol throughout subject participation in this study.
Liver biopsies
Subjects will have a liver biopsy for this study 12-14 weeks after transplantation. For subjects receiving darTregs, a second biopsy will be performed 7-10 days after darTregs infusion.
Liver transplantation
Inclusion in this trial is in the setting of subjects defined as having end-stage liver disease and listed for primary solitary liver transplant.
Cohort 2 - darTreg infusion,50 million(range 25 to 60 million)
At least 3 subjects will receive a single infusion of 50 million darTregs. Progression from one cohort to the next will depend on the cumulative incidence of sentinel adverse events.
Anti-Thymocyte Globulin - Rabbit
Liver transplantation/Treg-supportive immunosuppression (IS) treatment. Subjects will be given a dose range of 3.0-4.5 mg/kg total, in divided doses of 1.5 mg/kg/day. Subjects who meet eligibility criteria for Thymoglobulin® administration will be given 1.5 mg/kg intravenously (IV) on post-operative day 3, within 72 hours of transplantation. Additional doses of 1.5 mg/kg IV will be administered until CD3 count is \<50/mm\^3 or when the maximal dose of 4.5/mg/kg has been given.
darTreg Infusion
A single dose darTreg infusion (Cohorts 2 - 4) will be received as per protocol.
Everolimus
Liver transplantation/Treg-supportive immunosuppression (IS) treatment. Subjects meeting eligibility criteria for Treg-supportive IS regimen will begin EVR no sooner than 30 days after liver transplantation and no later than 44 days after transplantation; with target trough levels of 6-8 μg/L.EVR target trough levels will be further reduced to 4-6 μg/L 24 - 26 weeks after transplantation.
Tacrolimus
Liver transplantation/Treg-supportive immunosuppression (IS) treatment. Between 30 and 44 days following transplant: Subjects who are not eliminated by Exclusion Criteria C1 (Protocol Section 14.3.1) will proceed in the study and receive either TAC-based or EVR- based IS, based on eligibility Criteria C2 (Section 4.3.4 )
* TAC-based IS: reduce TAC trough level to 3-8 μg/dL; continue MMF
* EVR-based IS: reduce TAC trough level to 3-8 μg/dL; EVR target trough level of 6-8 μg/dL; decrease then discontinue MMF
Mycophenolate mofetil
Liver transplantation/Treg-supportive immunosuppression (IS) treatment. 1000 mg total daily dose. MMF will be initiated within 24 hours of transplantation. MMF must be discontinued as soon as target EVR trough levels have been achieved.
Prednisone
Liver transplantation/Treg-supportive immunosuppression (IS) treatment. Solumedrol 500 mg will be given IV on the day of transplantation. Additional Solumedrol will be prescribed according to site-specific standard of care. Oral prednisone should be initiated once oral medication is tolerated.
Acetaminophen
Pre-medication for single dose darTreg infusion (Cohorts 2 - 4). 650mg of acetaminophen will be administered intravenously or by mouth 30-60 minutes prior to the darTreg infusion.
Diphenhydramine
Pre-medication for single dose darTreg infusion (Cohorts 2 - 4). 25-50mg of diphenhydramine will be administered intravenously or by mouth 30-60 minutes prior to the darTreg infusion.
Anti-Infective Prophylaxis
Intravenous ganciclovir and/or oral Valcyte will be administered for the prophylaxis of cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) for at least six months after liver transplantation.
Leukapheresis
Leukapheresis is necessary to ensure collection of adequate numbers of autologous Tregs to support ex vivo expansion of darTregs for infusion after liver transplantation.
Participants enrolled in Cohorts 3 and 4 will undergo leukapheresis. Participants enrolled in Cohort 2 will have either whole blood collection or leukapheresis for the purpose of isolating autologous Tregs for later manufacture. If a cohort 2 subject has a hemoglobin level \>/=10.5 gm/dL, he or she will undergo phlebotomy. If the patient has a hemoglobin level \</=10.5 gm/dL and remains eligible for the study, the patient will undergo leukapheresis.
Blood draws
Blood draws are necessary to carefully and frequently evaluate allograft function after liver transplantation and treatment with Treg-supportive IS as well as after darTreg infusion. Peripheral blood samples will be collected and analyzed per protocol throughout subject participation in this study.
Liver biopsies
Subjects will have a liver biopsy for this study 12-14 weeks after transplantation. For subjects receiving darTregs, a second biopsy will be performed 7-10 days after darTregs infusion.
Liver transplantation
Inclusion in this trial is in the setting of subjects defined as having end-stage liver disease and listed for primary solitary liver transplant.
Cohort 3 - darTreg infusion,200 million(range100-240 million)
At least 3 subjects will receive a single infusion dose of 200 million darTregs. Progression from one cohort to the next will depend on the cumulative incidence of sentinel adverse events.
Anti-Thymocyte Globulin - Rabbit
Liver transplantation/Treg-supportive immunosuppression (IS) treatment. Subjects will be given a dose range of 3.0-4.5 mg/kg total, in divided doses of 1.5 mg/kg/day. Subjects who meet eligibility criteria for Thymoglobulin® administration will be given 1.5 mg/kg intravenously (IV) on post-operative day 3, within 72 hours of transplantation. Additional doses of 1.5 mg/kg IV will be administered until CD3 count is \<50/mm\^3 or when the maximal dose of 4.5/mg/kg has been given.
darTreg Infusion
A single dose darTreg infusion (Cohorts 2 - 4) will be received as per protocol.
Everolimus
Liver transplantation/Treg-supportive immunosuppression (IS) treatment. Subjects meeting eligibility criteria for Treg-supportive IS regimen will begin EVR no sooner than 30 days after liver transplantation and no later than 44 days after transplantation; with target trough levels of 6-8 μg/L.EVR target trough levels will be further reduced to 4-6 μg/L 24 - 26 weeks after transplantation.
Tacrolimus
Liver transplantation/Treg-supportive immunosuppression (IS) treatment. Between 30 and 44 days following transplant: Subjects who are not eliminated by Exclusion Criteria C1 (Protocol Section 14.3.1) will proceed in the study and receive either TAC-based or EVR- based IS, based on eligibility Criteria C2 (Section 4.3.4 )
* TAC-based IS: reduce TAC trough level to 3-8 μg/dL; continue MMF
* EVR-based IS: reduce TAC trough level to 3-8 μg/dL; EVR target trough level of 6-8 μg/dL; decrease then discontinue MMF
Mycophenolate mofetil
Liver transplantation/Treg-supportive immunosuppression (IS) treatment. 1000 mg total daily dose. MMF will be initiated within 24 hours of transplantation. MMF must be discontinued as soon as target EVR trough levels have been achieved.
Prednisone
Liver transplantation/Treg-supportive immunosuppression (IS) treatment. Solumedrol 500 mg will be given IV on the day of transplantation. Additional Solumedrol will be prescribed according to site-specific standard of care. Oral prednisone should be initiated once oral medication is tolerated.
Acetaminophen
Pre-medication for single dose darTreg infusion (Cohorts 2 - 4). 650mg of acetaminophen will be administered intravenously or by mouth 30-60 minutes prior to the darTreg infusion.
Diphenhydramine
Pre-medication for single dose darTreg infusion (Cohorts 2 - 4). 25-50mg of diphenhydramine will be administered intravenously or by mouth 30-60 minutes prior to the darTreg infusion.
Anti-Infective Prophylaxis
Intravenous ganciclovir and/or oral Valcyte will be administered for the prophylaxis of cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) for at least six months after liver transplantation.
Leukapheresis
Leukapheresis is necessary to ensure collection of adequate numbers of autologous Tregs to support ex vivo expansion of darTregs for infusion after liver transplantation.
Participants enrolled in Cohorts 3 and 4 will undergo leukapheresis. Participants enrolled in Cohort 2 will have either whole blood collection or leukapheresis for the purpose of isolating autologous Tregs for later manufacture. If a cohort 2 subject has a hemoglobin level \>/=10.5 gm/dL, he or she will undergo phlebotomy. If the patient has a hemoglobin level \</=10.5 gm/dL and remains eligible for the study, the patient will undergo leukapheresis.
Blood draws
Blood draws are necessary to carefully and frequently evaluate allograft function after liver transplantation and treatment with Treg-supportive IS as well as after darTreg infusion. Peripheral blood samples will be collected and analyzed per protocol throughout subject participation in this study.
Liver biopsies
Subjects will have a liver biopsy for this study 12-14 weeks after transplantation. For subjects receiving darTregs, a second biopsy will be performed 7-10 days after darTregs infusion.
Liver transplantation
Inclusion in this trial is in the setting of subjects defined as having end-stage liver disease and listed for primary solitary liver transplant.
Cohort 4 - darTreg infusion,800 million(range 400-960 million)
Six subjects will receive a single infusion of 800 million darTregs.
Anti-Thymocyte Globulin - Rabbit
Liver transplantation/Treg-supportive immunosuppression (IS) treatment. Subjects will be given a dose range of 3.0-4.5 mg/kg total, in divided doses of 1.5 mg/kg/day. Subjects who meet eligibility criteria for Thymoglobulin® administration will be given 1.5 mg/kg intravenously (IV) on post-operative day 3, within 72 hours of transplantation. Additional doses of 1.5 mg/kg IV will be administered until CD3 count is \<50/mm\^3 or when the maximal dose of 4.5/mg/kg has been given.
darTreg Infusion
A single dose darTreg infusion (Cohorts 2 - 4) will be received as per protocol.
Everolimus
Liver transplantation/Treg-supportive immunosuppression (IS) treatment. Subjects meeting eligibility criteria for Treg-supportive IS regimen will begin EVR no sooner than 30 days after liver transplantation and no later than 44 days after transplantation; with target trough levels of 6-8 μg/L.EVR target trough levels will be further reduced to 4-6 μg/L 24 - 26 weeks after transplantation.
Tacrolimus
Liver transplantation/Treg-supportive immunosuppression (IS) treatment. Between 30 and 44 days following transplant: Subjects who are not eliminated by Exclusion Criteria C1 (Protocol Section 14.3.1) will proceed in the study and receive either TAC-based or EVR- based IS, based on eligibility Criteria C2 (Section 4.3.4 )
* TAC-based IS: reduce TAC trough level to 3-8 μg/dL; continue MMF
* EVR-based IS: reduce TAC trough level to 3-8 μg/dL; EVR target trough level of 6-8 μg/dL; decrease then discontinue MMF
Mycophenolate mofetil
Liver transplantation/Treg-supportive immunosuppression (IS) treatment. 1000 mg total daily dose. MMF will be initiated within 24 hours of transplantation. MMF must be discontinued as soon as target EVR trough levels have been achieved.
Prednisone
Liver transplantation/Treg-supportive immunosuppression (IS) treatment. Solumedrol 500 mg will be given IV on the day of transplantation. Additional Solumedrol will be prescribed according to site-specific standard of care. Oral prednisone should be initiated once oral medication is tolerated.
Acetaminophen
Pre-medication for single dose darTreg infusion (Cohorts 2 - 4). 650mg of acetaminophen will be administered intravenously or by mouth 30-60 minutes prior to the darTreg infusion.
Diphenhydramine
Pre-medication for single dose darTreg infusion (Cohorts 2 - 4). 25-50mg of diphenhydramine will be administered intravenously or by mouth 30-60 minutes prior to the darTreg infusion.
Anti-Infective Prophylaxis
Intravenous ganciclovir and/or oral Valcyte will be administered for the prophylaxis of cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) for at least six months after liver transplantation.
Leukapheresis
Leukapheresis is necessary to ensure collection of adequate numbers of autologous Tregs to support ex vivo expansion of darTregs for infusion after liver transplantation.
Participants enrolled in Cohorts 3 and 4 will undergo leukapheresis. Participants enrolled in Cohort 2 will have either whole blood collection or leukapheresis for the purpose of isolating autologous Tregs for later manufacture. If a cohort 2 subject has a hemoglobin level \>/=10.5 gm/dL, he or she will undergo phlebotomy. If the patient has a hemoglobin level \</=10.5 gm/dL and remains eligible for the study, the patient will undergo leukapheresis.
Blood draws
Blood draws are necessary to carefully and frequently evaluate allograft function after liver transplantation and treatment with Treg-supportive IS as well as after darTreg infusion. Peripheral blood samples will be collected and analyzed per protocol throughout subject participation in this study.
Liver biopsies
Subjects will have a liver biopsy for this study 12-14 weeks after transplantation. For subjects receiving darTregs, a second biopsy will be performed 7-10 days after darTregs infusion.
Liver transplantation
Inclusion in this trial is in the setting of subjects defined as having end-stage liver disease and listed for primary solitary liver transplant.
Interventions
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Anti-Thymocyte Globulin - Rabbit
Liver transplantation/Treg-supportive immunosuppression (IS) treatment. Subjects will be given a dose range of 3.0-4.5 mg/kg total, in divided doses of 1.5 mg/kg/day. Subjects who meet eligibility criteria for Thymoglobulin® administration will be given 1.5 mg/kg intravenously (IV) on post-operative day 3, within 72 hours of transplantation. Additional doses of 1.5 mg/kg IV will be administered until CD3 count is \<50/mm\^3 or when the maximal dose of 4.5/mg/kg has been given.
darTreg Infusion
A single dose darTreg infusion (Cohorts 2 - 4) will be received as per protocol.
Everolimus
Liver transplantation/Treg-supportive immunosuppression (IS) treatment. Subjects meeting eligibility criteria for Treg-supportive IS regimen will begin EVR no sooner than 30 days after liver transplantation and no later than 44 days after transplantation; with target trough levels of 6-8 μg/L.EVR target trough levels will be further reduced to 4-6 μg/L 24 - 26 weeks after transplantation.
Tacrolimus
Liver transplantation/Treg-supportive immunosuppression (IS) treatment. Between 30 and 44 days following transplant: Subjects who are not eliminated by Exclusion Criteria C1 (Protocol Section 14.3.1) will proceed in the study and receive either TAC-based or EVR- based IS, based on eligibility Criteria C2 (Section 4.3.4 )
* TAC-based IS: reduce TAC trough level to 3-8 μg/dL; continue MMF
* EVR-based IS: reduce TAC trough level to 3-8 μg/dL; EVR target trough level of 6-8 μg/dL; decrease then discontinue MMF
Mycophenolate mofetil
Liver transplantation/Treg-supportive immunosuppression (IS) treatment. 1000 mg total daily dose. MMF will be initiated within 24 hours of transplantation. MMF must be discontinued as soon as target EVR trough levels have been achieved.
Prednisone
Liver transplantation/Treg-supportive immunosuppression (IS) treatment. Solumedrol 500 mg will be given IV on the day of transplantation. Additional Solumedrol will be prescribed according to site-specific standard of care. Oral prednisone should be initiated once oral medication is tolerated.
Acetaminophen
Pre-medication for single dose darTreg infusion (Cohorts 2 - 4). 650mg of acetaminophen will be administered intravenously or by mouth 30-60 minutes prior to the darTreg infusion.
Diphenhydramine
Pre-medication for single dose darTreg infusion (Cohorts 2 - 4). 25-50mg of diphenhydramine will be administered intravenously or by mouth 30-60 minutes prior to the darTreg infusion.
Anti-Infective Prophylaxis
Intravenous ganciclovir and/or oral Valcyte will be administered for the prophylaxis of cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) for at least six months after liver transplantation.
Leukapheresis
Leukapheresis is necessary to ensure collection of adequate numbers of autologous Tregs to support ex vivo expansion of darTregs for infusion after liver transplantation.
Participants enrolled in Cohorts 3 and 4 will undergo leukapheresis. Participants enrolled in Cohort 2 will have either whole blood collection or leukapheresis for the purpose of isolating autologous Tregs for later manufacture. If a cohort 2 subject has a hemoglobin level \>/=10.5 gm/dL, he or she will undergo phlebotomy. If the patient has a hemoglobin level \</=10.5 gm/dL and remains eligible for the study, the patient will undergo leukapheresis.
Blood draws
Blood draws are necessary to carefully and frequently evaluate allograft function after liver transplantation and treatment with Treg-supportive IS as well as after darTreg infusion. Peripheral blood samples will be collected and analyzed per protocol throughout subject participation in this study.
Liver biopsies
Subjects will have a liver biopsy for this study 12-14 weeks after transplantation. For subjects receiving darTregs, a second biopsy will be performed 7-10 days after darTregs infusion.
Liver transplantation
Inclusion in this trial is in the setting of subjects defined as having end-stage liver disease and listed for primary solitary liver transplant.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Able to understand and provide informed consent
* End-stage liver disease and listed for primary solitary liver transplant
* Have a calculated Model for End Stage Liver Disease (MELD) score ≤ 25 at the time of study entry/consent
* Female and male subjects with reproductive potential must agree to use effective methods of birth control for the duration of the study.
* If history of Hepatitis C Virus (HCV), have completed or are in current treatment for HCV AND have no detectable HCV RNA.
* Subjects with HCC meeting Milan criteria.
Exclusion Criteria
* History of less than 5 years remission of malignancy, except for 1) HCC or 2) history of adequately treated in-situ cervical carcinoma, or adequately treated basal or squamous cell carcinoma of the skin.
* History of previous organ, tissue or cell transplant
* Serologic evidence of human immunodeficiency (HIV) 1 or -2 infection
* Epstein-Barr Virus (EBV) or cytomegalovirus (CMV) sero-negativity (EBV or CMV naïve candidates)
* Chronic use of systemic glucocorticoids or other Immunosuppression (IS), or biologic immunomodulators
* Chronic condition requiring anti-coagulation after liver transplantation
* Any chronic illness or prior treatment which, in the opinion of the investigator, precludes study participation
* Participation in any other studies that involved investigational drugs or regimens in the preceding year
* Received any vaccination within 28 days prior to leukapheresis or blood collection for Treg manufacture
* Hemoglobin \<9.0 g/dL within 10 days prior to screening
* Neutrophils \<1,500/μL within 10 days prior to screening
* Platelets \<40,000/μL within 10 days prior to screening
* Calculated Model for End Stage Liver Disease (MELD) score \>25 at the time of deceased donor liver transplant
* Last alpha-fetoprotein (AFP) obtained prior to liver transplantation \>400 μg/L for candidates with Hepatocellular Carcinoma (HCC)
* Unacceptable Peripheral Blood Mononuclear Cells (PBMC) product for participants enrolled in Cohorts 2, 3, or 4 per the UCSF The Human Islet and Cellular Transplant Facility (HICTF) manufacturing specifications
* Absence of donor spleen for any participants
* Human leukocyte antigen (HLA)-DR (DR is one of class II antigens) matched to donor at both loci
* Subject is \< 21 or \>70 years of age at the time of transplantation
* Located in the intensive care unit 72 hours after transplantation
* Hemoglobin \<8.0 g/dL
* Absolute neutrophil count \<1,200/μL
* Platelets \<40,000/μL
* Positive pregnancy test for females of child bearing potential
* Unexpected histopathology on back table liver biopsy that contraindicates the initiation of Treg supportive IS regimen.
* Development of a condition requiring chronic anti-coagulation.
* Hypersensitivity to rabbit proteins or any excipient in Thymoglobulin®.
* Detectable HCV RNA or less than six months after end of treatment for HCV at the time of transplantation (i.e., does not meet criteria for SVR).
* Explanted liver with evidence of increased risk of recurrent cancer risk (hepatocellular (HCC) tumor burden exceeding the Milan criteria; presence of vascular invasion; cholangiocarcinoma morphology)
* Insufficient depletion of recipient T cells, defined as a nadir CD3 count ≥50 cells μ/L (50 cells /mcL) or total lymphocyte count ≥ 0.1x 109/L if CD3 count is unavailable
* Development of a condition requiring chronic anti-coagulation.
* Clinical evidence of biliary obstruction
* Alanine Aminotransferase (ALT) \>2.0 x upper limit of normal (ULN)
* Inability to taper off corticosteroids by 44 days (+/- 2 days) after transplant
* Detectable circulating HCV RNA.
Everolimus Conversion Criteria C2 (assessed prior to conversion to EVR based IS regimen; EVR cannot be initiated prior to 30 days after liver transplantation). Subjects with any of the following will remain on TAC-based IS regimen.
* Evidence of hepatic artery stenosis or thrombosis by Doppler examination or angiography within 7 days prior to conversion
* Urine protein/creatinine ratio \>1.0 within 7 days prior to conversion
* Calculated GFR less than 30 ml/min per MDRD4 (Modification of Diet in Renal Disease Study) equation within 7 days prior to conversion
* Physical examination documentation of abnormal wound healing or uncontrolled wound infection
* Hemoglobin \<8.0 g/dL within 7 days prior to conversion
* Absolute neutrophil count \<1,200/μL within 7 days prior to conversion
* Platelets \<50,000/μL within 7 days prior to conversion
* Inability or unwillingness of participant to give additional written informed consent
* Unacceptable darTreg product
* Detectible circulating Epstein-Barr Virus (EBV) or cytomegalovirus (CMV) DNA within 10 days prior to darTreg infusion
* Detectible Hepatitis B Virus (HBV) DNA within 10 days prior to darTreg infusion
* Detectable circulating HCV RNA within 10 days prior to darTreg infusion.
* Alanine Aminotransferase (ALT) \>1.5x upper limit of normal within 10 days of darTreg infusion
* Most recent, but not greater than 10 days prior to darTreg infusion,12 hour TAC trough levels of \> 8 μg/L for all subjects
* Most recent, but not greater than 10 days prior to darTreg infusion,12 hour EVR trough levels of \< 5 μg/L for subjects on EVR
* For subjects on EVR-based IS, received Mycophenolate Mofetil (MMF) within 10 days prior to darTreg infusion
* Evidence of acute rejection or chronic rejection according to Banff criteria on protocol allograft biopsy based on local assessment
* Received any vaccination within 14 days prior to darTreg infusion
* Positive pregnancy test for females of child bearing potential
* Inability or unwillingness of participant to comply with study protocol or procedures.
* Calculated glomerular filtration rate (eGFR) less than 40 ml/min per MDRD4 equation within 10 days prior to infusion.
21 Years
70 Years
ALL
No
Sponsors
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Rho Federal Systems Division, Inc.
INDUSTRY
National Institute of Allergy and Infectious Diseases (NIAID)
NIH
Responsible Party
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Principal Investigators
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Sandy Feng, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
University of California, San Francisco
Jeffrey Bluestone, PhD
Role: PRINCIPAL_INVESTIGATOR
University of California, San Francisco
Sang-Mo Kang, MD, FACS
Role: PRINCIPAL_INVESTIGATOR
University of California, San Francisco
Qizhi Tang, PhD
Role: PRINCIPAL_INVESTIGATOR
University of California, San Francisco
Locations
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University of California, San Francisco
San Francisco, California, United States
Northwestern University
Chicago, Illinois, United States
Mayo Clinic
Rochester, Minnesota, United States
Countries
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Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Related Links
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National Institute of Allergy and Infectious Diseases (NIAID) website
Other Identifiers
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