Immune System Suppression With Alemtuzumab and Tacrolimus in Liver Transplantation Patients

NCT ID: NCT00105235

Last Updated: 2012-12-27

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

27 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-06-30

Study Completion Date

2011-03-31

Brief Summary

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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.

Detailed Description

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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 Regimens that are less toxic to or can eventually be withdrawn from transplant recipients are needed.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 This study will also determine if post-transplant tacrolimus therapy can be slowly and safely tapered off and withdrawn a year after transplant.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.

Conditions

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Liver Disease Liver Transplantation

Keywords

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transplantation liver transplant rejection tolerance antibody induction

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Alemtuzumab

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

Group Type EXPERIMENTAL

Alemtuzumab

Intervention Type DRUG

T-cell depleting monoclonal antibody; two doses by intravenous infusion on Days 0 and 4

Cyclosporine

Intervention Type DRUG

Oral immunosuppressant

Mycophenolate mofetil

Intervention Type DRUG

Oral immunosuppressant

Tacrolimus

Intervention Type DRUG

Oral immunosuppressant

Liver transplant

Intervention Type PROCEDURE

Occurs at study entry

Immunosuppression withdrawal

Intervention Type PROCEDURE

Beginning no earlier than Year 1

Interventions

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Alemtuzumab

T-cell depleting monoclonal antibody; two doses by intravenous infusion on Days 0 and 4

Intervention Type DRUG

Cyclosporine

Oral immunosuppressant

Intervention Type DRUG

Mycophenolate mofetil

Oral immunosuppressant

Intervention Type DRUG

Tacrolimus

Oral immunosuppressant

Intervention Type DRUG

Liver transplant

Occurs at study entry

Intervention Type PROCEDURE

Immunosuppression withdrawal

Beginning no earlier than Year 1

Intervention Type PROCEDURE

Other Intervention Names

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Campath CellCept FK-506 Fujimycin

Eligibility Criteria

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Inclusion Criteria

* Diagnosis of nonimmune, nonviral, end-stage liver disease
* Need liver transplant
* Willing to use acceptable means of contraception for the duration of the study

Exclusion Criteria

* Previous transplant
* Multiorgan transplant or living donor transplant
* Donor liver from a donor positive for antibody against hepatitis B core antigen or hepatitis C virus
* Donor liver from a non-heart-beating donor
* Liver failure due to autoimmune disease, such as autoimmune hepatitis, primary sclerosing cholangitis, or primary biliary cirrhosis
* Hepatitis B or C virus infection
* HIV infection
* Stage III or higher hepatocellular cancer based on pre-transplant imaging
* History of cancer. Patients with hepatocellular cancer, adequately treated in situ cervical carcinoma, or adequately treated basal or squamous cell carcinoma of skin are not excluded.
* Active systemic infection at the time of transplantation
* Clinically significant chronic renal, cardiovascular, or cerebrovascular disease
* Any investigational drug within 6 weeks of study entry
* Hypersensitivity to alemtuzumab or tacrolimus
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Immune Tolerance Network (ITN)

NETWORK

Sponsor Role collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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J. Richard Thistlethwaite, MD

Role: PRINCIPAL_INVESTIGATOR

University of Chicago

Locations

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University of California, San Francisco

San Francisco, California, United States

Site Status

University of Colorado

Denver, Colorado, United States

Site Status

University of Miami School of Medicine

Miami, Florida, United States

Site Status

University of Michigan

Ann Arbor, Michigan, United States

Site Status

Cleveland Clinic

Cleveland, Ohio, United States

Site Status

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Baylor University

Dallas, Texas, United States

Site Status

University of Wisconsin

Madison, Wisconsin, United States

Site Status

University of Alberta

Edmonton, Alberta, Canada

Site Status

Countries

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United States Canada

References

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First MR. Tacrolimus based immunosuppression. J Nephrol. 2004 Nov-Dec;17 Suppl 8:S25-31.

Reference Type BACKGROUND
PMID: 15599882 (View on PubMed)

Tryphonopoulos P, Madariaga JR, Kato T, Nishida S, Levi DM, Moon J, Selvaggi G, De Faria W, Regev A, Bejarano P, Khaled A, Safdar K, Esquenazi V, Weppler D, Yoshida H, Ruiz P, Miller J, Tzakis AG. The impact of Campath 1H induction in adult liver allotransplantation. Transplant Proc. 2005 Mar;37(2):1203-4. doi: 10.1016/j.transproceed.2004.12.157.

Reference Type BACKGROUND
PMID: 15848669 (View on PubMed)

Tzakis AG, Tryphonopoulos P, Kato T, Nishida S, Levi DM, Madariaga JR, Gaynor JJ, De Faria W, Regev A, Esquenazi V, Weppler D, Ruiz P, Miller J. Preliminary experience with alemtuzumab (Campath-1H) and low-dose tacrolimus immunosuppression in adult liver transplantation. Transplantation. 2004 Apr 27;77(8):1209-14. doi: 10.1097/01.tp.0000116562.15920.43.

Reference Type BACKGROUND
PMID: 15114087 (View on PubMed)

Related Links

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http://www.immunetolerance.org

Click here for the Immune Tolerance Network Web site

Other Identifiers

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DAIT ITN024ST

Identifier Type: -

Identifier Source: org_study_id