Immune System Suppression With Alemtuzumab and Tacrolimus in Liver Transplantation Patients

NCT00105235 | Completed Phase 2 Results DMC

• 1 other identifier: DAIT ITN024ST
• Study Type: interventional
• Target: 27
• Locations: 2 countries
• Sites: 9

Brief Summary

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.

Conditions

Liver Disease; Liver Transplantation

Keywords

transplantation; liver transplant; rejection; tolerance; antibody induction

Outcome Measures

Primary Outcomes (1)

• Proportion of Participants Who Have Graft Loss or Death

  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.

  Within 1 year of post-transplantation

Secondary Outcomes (4)

• Proportion of Participants Who Had Graft Loss or Death

  Within 2 years after initiation of immunosuppression withdrawal

• Number of Events: Immunosuppression-related Complications

  From transplantation until study completion or participant termination (participants followed up to 60 months)

• Proportion of Participants Successfully Withdrawn From Immunosuppressants

  From 1 year post- transplantation until study completion or participant termination (participants followed up to 48 months post-transplant)

• Proportion of Participants Successfully Withdrawn and Remain Off Immunosuppressants

  From 1 year post- transplantation until study completion or participant termination (participants followed up to 48 months post-transplant)

Study Arms (1)

Alemtuzumab

EXPERIMENTAL

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

Drug: Alemtuzumab; Drug: Cyclosporine; Drug: Mycophenolate mofetil; Drug: Tacrolimus; Procedure: Liver transplant; Procedure: Immunosuppression withdrawal

Interventions

Alemtuzumab DRUG

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

Also known as: Campath

Alemtuzumab

Cyclosporine DRUG

Oral immunosuppressant

Alemtuzumab

Mycophenolate mofetil DRUG

Oral immunosuppressant

Also known as: CellCept

Alemtuzumab

Tacrolimus DRUG

Oral immunosuppressant

Also known as: FK-506, Fujimycin

Alemtuzumab

Liver transplant PROCEDURE

Occurs at study entry

Alemtuzumab

Immunosuppression withdrawal PROCEDURE

Beginning no earlier than Year 1

Alemtuzumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Immune Tolerance Network (ITN): collaborator

Study Sites (9)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

University of Colorado

Denver, Colorado, 80262, United States

Location

University of Miami School of Medicine

Miami, Florida, 33101, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Baylor University

Dallas, Texas, 75246, United States

Location

University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

University of Alberta

Edmonton, Alberta, Canada

Location

Related Publications (3)

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

  PMID: 15599882 BACKGROUND

• 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.

  PMID: 15848669 BACKGROUND

• 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.

  PMID: 15114087 BACKGROUND

Related Links

• Click here for the Immune Tolerance Network Web site

MeSH Terms

Conditions

Liver Diseases; Rejection, Psychology

Interventions

Alemtuzumab; Cyclosporine; Mycophenolic Acid; Tacrolimus; Liver Transplantation

Condition Hierarchy (Ancestors)

Digestive System Diseases; Social Behavior; Behavior

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Macrolides; Lactones; Tissue Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Digestive System Surgical Procedures; Surgical Procedures, Operative; Organ Transplantation; Transplantation

Limitations and Caveats

This study was converted to a pilot study on May 23, 2006. Only 27 of the planned 211 participants were enrolled, thus reducing the number of subjects available for analysis.

Results Point of Contact

• Title: Associate Director, Clinical Research Program
• Organization: DAIT/NIAID

DAITClinicalTrialsGov@niaid.nih.gov

301-594-7669

Study Officials

• J. Richard Thistlethwaite, MD

  University of Chicago

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 10, 2005
• First Posted: March 11, 2005
• Study Start: June 1, 2005
• Primary Completion: March 1, 2007
• Study Completion: March 1, 2011
• Last Updated: December 27, 2012
• Results First Posted: April 5, 2012

Record last verified: 2012-11

Locations

US (8); CA (1)