Immune System Suppression With Alemtuzumab and Tacrolimus in Liver Transplantation Patients (TILT)
Alemtuzumab is a man-made antibody used to treat certain blood disorders. Tacrolimus is a drug used to decrease immune system activity in people who have received organ transplants so that the new organ will not be rejected. This study will determine whether treatment with alemtuzumab and tacrolimus is effective in preventing organ rejection and maintaining the recipient's health after liver transplantation in patients with end-stage liver disease, and whether gradual tapering of tacrolimus treatment is safe for these patients.
Drug: Mycophenolate mofetil
Procedure: Liver transplant
Procedure: Immunosuppression withdrawal
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Multicenter Trial to Assess the Safety and Efficacy of Campath-1H and Tacrolimus Followed By Immunosuppression Withdrawal in Liver Transplantation (ITN024ST)|
- Proportion of Participants Who Have Graft Loss or Death [ Time Frame: Within 1 year of post-transplantation ] [ Designated as safety issue: Yes ]Proportion of participants who had liver graft loss or who died within 1 year of undergoing transplantation. Note: Participants who discontinued treatment or terminated the study prior to 1 year post transplantation are considered treatment failures and are included in this measure.
- Proportion of Participants Who Had Graft Loss or Death [ Time Frame: Within 2 years after initiation of immunosuppression withdrawal ] [ Designated as safety issue: Yes ]Proportion of participants who had liver graft loss or who died or terminated from the study within 2 years of initiating immunosuppression withdrawal
- Number of Events: Immunosuppression-related Complications [ Time Frame: From transplantation until study completion or participant termination (participants followed up to 60 months) ] [ Designated as safety issue: Yes ]Certain events are associated with immunosuppression. This measure looks at post-transplant infection, post-transplant malignancies, post-transplant diabetes, and post-transplant renal failure. Immunosuppression withdrawal is intended to reduce these type of events. However, reduction in immunosuppression can lead to complications in liver and renal function, as measured by acute rejection, chronic rejection, and post-transplant renal failure. Lower numbers for any of these events indicates greater success with transplantation and immunosuppression withdrawal (where applicable)
- Proportion of Participants Successfully Withdrawn From Immunosuppressants [ Time Frame: From 1 year post- transplantation until study completion or participant termination (participants followed up to 48 months post-transplant) ] [ Designated as safety issue: Yes ]This measure of tolerance induction includes the proportion of participants who qualify for immunosuppression withdrawal as determined by a review of individual clinical results by a protocol withdrawal committee. Successful withdrawal definition: participants who remain off immunosuppression for at least 8 weeks.
- Proportion of Participants Successfully Withdrawn and Remain Off Immunosuppressants [ Time Frame: From 1 year post- transplantation until study completion or participant termination (participants followed up to 48 months post-transplant) ] [ Designated as safety issue: No ]This measure of tolerance induction includes the proportion of participants who qualify for immunosuppression withdrawal as determined by a review of individual clinical results by a protocol withdrawal committee, were successfully withdrawn from immunosuppressants, and remained off immunosuppressants at the time the trial ended. Successful withdrawal definition: participants who remain off immunosuppression for at least 8 weeks and do not restart immunosuppressant drugs after successful withdrawal.
|Study Start Date:||June 2005|
|Study Completion Date:||March 2011|
|Primary Completion Date:||March 2007 (Final data collection date for primary outcome measure)|
Liver transplant, with two in-patient infused doses of alemtuzumab; followed by maintenance immunotherapy with cyclosporine, mycophenolate mofetil, and/or tacrolimus; with possible immunosuppression withdrawal
T-cell depleting monoclonal antibody; two doses by intravenous infusion on Days 0 and 4
Other Name: CampathDrug: Cyclosporine
Oral immunosuppressantDrug: Mycophenolate mofetil
Other Name: CellCeptDrug: Tacrolimus
Other Names:Procedure: Liver transplant
Occurs at study entryProcedure: Immunosuppression withdrawal
Beginning no earlier than Year 1
Organ transplantation is a common procedure in hospitals, but organ rejection and serious side effects are potential problems for the patient. Alemtuzumab is a monoclonal antibody that binds to and depletes excess T cells in the bone marrow of leukemia patients. In this study, alemtuzumab will destroy the recipient's white blood cells (WBCs) at the time of transplantation. It is hoped that WBCs produced after alemtuzumab administration will recognize the transplanted liver as "self" and not reject the new liver.
Drugs that suppress the immune system, such as tacrolimus, have contributed to increased success of transplantation. However, to prevent organ rejection, transplant recipients need to take immunosuppressive drugs for the rest of their lives, and these drugs make patients more susceptible to infection, endangering their health and survival. Regimens that are less toxic to or can eventually be withdrawn from transplant recipients are needed. This study will evaluate the effects of two in-patient doses of alemtuzumab followed by maintenance antirejection medication given to liver transplant patients post-transplant. This study will also determine if post-transplant tacrolimus therapy can be slowly and safely tapered off and withdrawn a year after transplant. Participants in this study will be patients with end-stage liver disease who will undergo liver transplantation at the start of the study.
This study will last at least 2 years. Patients will undergo liver transplantation at the start of the study on Day 0. Patients will receive in-patient infusions of alemtuzumab on Days 0 and 4. Starting on Day 1, patients will receive oral cyclosporine, mycophenolate mofetil, and/or tacrolimus daily. Patients will be hospitalized for at least 1 week after transplantation. Because of suppression of patients' immune systems by alemtuzumab and these other immunosuppressants, they will also receive prophylactic medications for a minimum of 3 months after transplantation to prevent opportunistic infections.
There will be at least eight study visits; they will occur at Days 4, 7, and 14 and at Months 1, 3, 6, 9, and 12. Patients will have liver biopsies at Day 0 and Months 6 and 12. At Month 12, participants will have assessments and blood tests to determine if they meet certain criteria and are eligible to undergo tacrolimus tapering. Patients eligible for tapering will undergo a 12-month gradual withdrawal of tacrolimus; they will be followed for an additional 2 years, with study visits at Months 18, 24, 30, and 36. Patients ineligible for tacrolimus tapering will continue taking their antirejection medication for the duration of the study; they will be followed for an additional year, with study visits at Months 18 and 24.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00105235
|United States, California|
|University of California, San Francisco|
|San Francisco, California, United States, 94143|
|United States, Colorado|
|University of Colorado|
|Denver, Colorado, United States, 80262|
|United States, Florida|
|University of Miami School of Medicine|
|Miami, Florida, United States, 33101|
|United States, Michigan|
|University of Michigan|
|Ann Arbor, Michigan, United States, 48109|
|United States, Ohio|
|Cleveland, Ohio, United States, 44195|
|United States, Pennsylvania|
|University of Pennsylvania|
|Philadelphia, Pennsylvania, United States, 19104|
|United States, Texas|
|Dallas, Texas, United States, 75246|
|United States, Wisconsin|
|University of Wisconsin|
|Madison, Wisconsin, United States, 53792|
|University of Alberta|
|Edmonton, Alberta, Canada|
|Principal Investigator:||J. Richard Thistlethwaite, MD||University of Chicago|