A Trial of Two Steroid-Free Approaches Toward Mycophenolate Mofetil-Based Monotherapy Immunosuppression (Cell220)

October 20, 2015 updated by: Joseph Leventhal, Northwestern University

A Phase IV, Single Center Pilot Study Using Alemtuzumab (Campath-1H) Induction Combined With Prednisone-Free, Calcineurin-Inhibitor-Free Immunosuppression in Kidney Transplantation

This is an open label, single-center, randomized phase IV pilot study of steroid and calcineurin inhibitor avoidance in renal transplant recipients. All patients will receive two doses of alemtuzumab to achieve peripheral T-cell depletion. Intravenous glucocorticoids will be administered prior to alemtuzumab administration to limit cytokine release syndrome in association with this monoclonal antibody, and continued for the first two days post-transplant. Thereafter, steroids will not be used for immunosuppression. All transplant recipients will be started on oral immunosuppressive therapy with mycophenolate mofetil (MMF) prior to transplant. Pretransplant, these patients will be randomized to receive, in addition, either tacrolimus (Tac) or sirolimus.

After six months, patients in the tacrolimus arm who do not experience rejection will be randomized to continue on tacrolimus or to be converted to the combination of sirolimus and MMF. Individuals in this arm of the study who do not experience acute rejection, and demonstrate evidence of donor specific hyporesponsiveness at 9 months post-transplant (those staying on Tac + MMF) or 3 months post-conversion (those converted from Tac + MMF to sirolimus + MMF) will be weaned to MMF monotherapy.

Individuals in the sirolimus + MMF arm who do not experience acute rejection and demonstrate evidence of donor specific hyporesponsiveness at 6 months post-transplant will be weaned to MMF monotherapy.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

40

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University/Northwestern Memorial Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Patients who are male or female age 18-65 years
  2. Donor age 18-65 years
  3. Patients who are single-organ recipients (kidney only)
  4. Women who are of childbearing potential must have a negative serum pregnancy test before transplantation and agree to use a medically acceptable method of contraception throughout the treatment period.
  5. Subject (recipient) is able to understand the consent form and give written informed consent

Exclusion Criteria:

  1. Known sensitivity or contraindication to sirolimus, tacrolimus or MMF
  2. Patient with significant or active infection
  3. Patients with a positive lymphocytotoxic crossmatch using donor lymphocytes and recipient serum
  4. Patients with PRA > 20%
  5. Patients who are pregnant or nursing mothers
  6. Patients whose life expectancy is severely limited by diseases other than renal disease
  7. Ongoing active substance abuse, drug or alcohol
  8. Major ongoing psychiatric illness or recent history of noncompliance

  9. Significant cardiovascular disease (e.g.):

    • Significant non-correctable coronary artery disease
    • Ejection fraction below 30%
    • History of recent myocardial infarction
  10. Malignancy within 3 years, excluding non-melanoma skin cancers
  11. Serologic evidence of infection with HIV or HBVsAg positive
  12. Patients with a screening/baseline total white blood cell count < 4,000/mm3; platelet count < 100,000/mm3; triglycerides > 400 mg/dl; total cholesterol > 300 mg/dl
  13. Investigational drug within 30 days prior to transplant surgery
  14. Anti-T cell therapy within 30 days prior to transplant surgery
  15. Patients using Prednisone
  16. Patients who are ABO incompatible

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Group 1: Alemtuzumab + TAC + MMF
Receive two doses of alemtuzumab (Campath-1H, 30mg) by intravenous (IV) infusion. One dose during kidney transplant surgery and the second dose on day 2 (post-surgery) to achieve peripheral T-cell depletion. IV glucocorticoids will be given prior to Campath administration to limit cytokine release syndrome in association with this monoclonal antibody. MMF on the day of surgery and continue taking it by mouth, twice daily. TAC started on the 1st day after surgery, and then taken by mouth twice daily.
Drug: Tacrolimus (TAC)
Tacrolimus (TAC) will be given standard of care by prescription twice a day (2.0 mg), orally. Doses will be adjusted by serum levels. The dose will be modified to achieve 12 hour trough concentrations of 5-8 ng/mL.
Other Names:
  • FK506
  • Prograf®
Drug: Alemtuzumab
Patients receiving alemtuzumab will be premedicated with 50mg of diphenhydramine hydrochloride, and 650mg of acetaminophen 30-60 minutes to the first Alemtuzumab infusion. The of 30mg will be diluted in 100cc sterile 0.9% normal saline and infused over 2 hours. The infusion line must contain an in-line 0.22-micron filter. Alemtuzumab will be administered on the day of transplant (intraoperatively), and on post-operative day 2. Both doses will be administered while the patient is in the hospital. Alemtuzumab is supplied in single-use clear glass ampoules containing 30mg of alemtuzumab in 3mL of solution.
Other Names:
  • Campath-1H
  • Campath®
  • Mabcampath®
Drug: Mycophenolate mofetil (MMF)
MMF will be given at 1.0-1.5gm, twice daily, orally. The first dose will be given pre-transplant, open label fashion.
Other Names:
  • Cellcept®
Active Comparator: Group 2: Alemtuzumab + Sirolimus + MMF

Sirolimus will be taken by mouth before transplant surgery and will continue taking once daily after surgery. Group 2 will also receive 2 doses of Alemtuzumab: one during surgery and the second will be given on the second day after surgery. Mycophenolate mofetil will be give on the day of surgery and twice daily, by mouth, as instructed by the doctor.

If subjects do not experience kidney rejection after 6 months after surgery, they will be weaned off of the sirolimus and continue taking the mycophenolate mofetil.
Drug: Alemtuzumab
Patients receiving alemtuzumab will be premedicated with 50mg of diphenhydramine hydrochloride, and 650mg of acetaminophen 30-60 minutes to the first Alemtuzumab infusion. The of 30mg will be diluted in 100cc sterile 0.9% normal saline and infused over 2 hours. The infusion line must contain an in-line 0.22-micron filter. Alemtuzumab will be administered on the day of transplant (intraoperatively), and on post-operative day 2. Both doses will be administered while the patient is in the hospital. Alemtuzumab is supplied in single-use clear glass ampoules containing 30mg of alemtuzumab in 3mL of solution.
Other Names:
  • Campath-1H
  • Campath®
  • Mabcampath®
Drug: Mycophenolate mofetil (MMF)
MMF will be given at 1.0-1.5gm, twice daily, orally. The first dose will be given pre-transplant, open label fashion.
Other Names:
  • Cellcept®
Drug: Sirolimus
Sirolimus will be given standard of care by prescription, dosed at 5mg daily. The dosage will be adjusted by serum level to achieve 24 hour trough concentrations of 8-12 ng/mL by HPLC assay.
Other Names:
  • Rapamycin
  • Rapamune®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The Incidence of Biopsy-proven Acute Allograft Rejection During the First 12 Months of Transplant.
Time Frame: Within 12 months post kidney transplant
The incidence of rejection is determined by the proportion of patients experiencing biopsy proven acute allograft rejection during the first 12 months post-transplant.
Within 12 months post kidney transplant

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Severity of Acute Rejection During the First 6 and 12 Months Post-transplant
Time Frame: Months 6-12 post-transplant
The diagnosis of rejection will be based on clinical symptoms and signs, laboratory tests, and confirmed by core renal allograft biopsy.
Months 6-12 post-transplant
Renal Function at 12 Months Post-transplant
Time Frame: At 12 months post-transplant
Laboratory tests for renal function include creatinine or iothalamate glomerular filtration rate (GFR).
At 12 months post-transplant
Incidence of Donor Specific Hyporesponsiveness Allowing for the Conversion to Monotherapy
Time Frame: At 6 & 9 months post-transplant
The proportion of subjects for both groups determine this measure: 1) Patients in tacrolimus arm who do not experience acute rejection and demonstrate evidence of donor specific hyporesonsiveness at 9 months post-transplant (those staying on TAC+MMF) or 3 months post-convertion (converted from TAC+MMF to Sirolimus+MMF) will be weaned to MMF monotherapy; 2) Those in the sirolimus+MMF arm who do not experience acute rejection and demonstrate evidence of donor specific hyporesponsiveness at 6 months post-transplant will be weaned to MMF monotherapy.
At 6 & 9 months post-transplant
Patient and Graft Survival Rates at 6 and 12 Months Post-transplant
Time Frame: At 6 & 12 months post-transplant
At 6 & 12 months post-transplant

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Northwestern University

Collaborators

Roche Pharma AG

Investigators

  • Principal Investigator: Joseph R Leventhal, MD, PhD, Northwestern University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2005

Primary Completion (Actual)

April 1, 2010

Study Completion (Actual)

April 1, 2010

Study Registration Dates

First Submitted

September 9, 2005

First Submitted That Met QC Criteria

September 9, 2005

First Posted (Estimate)

September 14, 2005

Study Record Updates

Last Update Posted (Estimate)

October 26, 2015

Last Update Submitted That Met QC Criteria

October 20, 2015

Last Verified

October 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STU8789 0811-007
  • CNV0042139 (Other Grant/Funding Number: Roche Laboratories, Inc.)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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