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Liver DiseasePhase 2TILTNCT00105235

Immune System Suppression With Alemtuzumab and Tacrolimus in Liver Transplantation Patients

A Phase 2 study testing Alemtuzumab, Cyclosporine and Mycophenolate mofetil in people with Liver Disease and Liver Transplantation, run by National Institute of Allergy and Infectious Diseases (NIAID) at 9 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Liver Disease, Liver Transplantation
What is being tested?
Alemtuzumab, Cyclosporine and Mycophenolate mofetil
Could I receive a placebo?
No, everyone receives an active treatment
How many people
27 participants
Where
9 sitesin 2 countries
Study dates
Jun 2005to Mar 2011
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

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

Who cannot join

  • 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
Show all 13Show fewer
  • 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

Trial locations and contacts

9 sites in 2 countries.

9 sites in 2 countries

United States8 sites

  • University of Michigan

    Ann Arbor, Michigan, 48109

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • Baylor University

    Dallas, Texas, 75246

  • University of Colorado

    Denver, Colorado, 80262

  • University of Wisconsin

    Madison, Wisconsin, 53792

  • University of Miami School of Medicine

    Miami, Florida, 33101

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • University of California, San Francisco

    San Francisco, California, 94143

Other trials in United States

Canada1 site

  • University of Alberta

    Edmonton, Alberta

Other trials in Canada

About this study

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)

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.

Read the detailed description

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.

Being tested
Alemtuzumab, Cyclosporine, Mycophenolate mofetil, Tacrolimus, Liver transplant
Keywords
transplantation, liver transplant, rejection, tolerance, antibody induction
Medical subject headings
Liver Diseases, Rejection, Psychology

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AlemtuzumabDrug

    Also called Campath

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

  • CyclosporineDrug

    Oral immunosuppressant

  • Mycophenolate mofetilDrug

    Also called CellCept

    Oral immunosuppressant

  • TacrolimusDrug

    Also called FK-506, Fujimycin

    Oral immunosuppressant

  • Liver transplantProcedure or surgery

    Occurs at study entry

  • Immunosuppression withdrawalProcedure or surgery

    Beginning no earlier than Year 1

Study groups in NCT00105235
Study groupRoleWhat they receive
AlemtuzumabExperimentalLiver transplant, with two in-patient infused doses of alemtuzumab; followed by maintenance immunotherapy with cyclosporine, mycophenolate mofetil, and/or tacrolimus; with possible immunosuppression withdrawal
Receives: Drug: Alemtuzumab; Drug: Cyclosporine; Drug: Mycophenolate mofetil; Drug: Tacrolimus; Procedure: Liver transplant; Procedure: Immunosuppression withdrawal

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Within 1 year of post-transplantation

Secondary outcomes (4)

  1. Proportion of Participants Who Had Graft Loss or Death

    Proportion of participants who had liver graft loss or who died or terminated from the study within 2 years of initiating immunosuppression withdrawal

    Measured: Within 2 years after initiation of immunosuppression withdrawal

  2. Number of Events: Immunosuppression-related Complications

    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)

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

  3. Proportion of Participants Successfully Withdrawn From Immunosuppressants

    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.

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

  4. Proportion of Participants Successfully Withdrawn and Remain Off Immunosuppressants

    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.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Mar 2005 (estimated)
  2. Study startJun 2005
  3. Primary completionMar 2007
  4. Study completionMar 2011

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
27 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00105235
Sponsor's protocol ID
DAIT ITN024ST
Acronym
TILT
Status last verified
Nov 2012
First submitted
10 Mar 2005
Last updated
27 Dec 2012
Data monitoring committee
Yes

Publications

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

    PubMed 15599882

  • 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.

    PubMed 15848669

  • 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.

    PubMed 15114087

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Alemtuzumab, Cyclosporine and Mycophenolate mofetil in people with Liver Disease and Liver Transplantation, run by National Institute of Allergy and Infectious Diseases (NIAID) at 9 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Dec 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Apr 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of Participants Who Have Graft Loss or Death (time frame: Within 1 year of post-transplantation). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00105235, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Dec 2012.

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