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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2010 by Northwestern University.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Northwestern Memorial Hospital
Information provided by:
Northwestern University
ClinicalTrials.gov Identifier:
NCT00166712
First received: September 9, 2005
Last updated: September 30, 2010
Last verified: September 2010
  Purpose

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 (Campath-1H, 30mg); one at the time of renal transplant, and one on post-operative day two to achieve peripheral T-cell depletion. Intravenous glucocorticoids will be administered prior to Campath 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.


Condition Intervention Phase
Kidney Transplantation
Drug: Tacrolimus
Drug: Sirolimus
Drug: Alemtuzumab
Drug: Mycophenolate mofetil
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase IV, Single Center Pilot Study Using Alemtuzumab (Campath-1H) Induction Combined With Prednisone-Free, Calcineurin-Inhibitor-Free Immunosuppression in Kidney Transplantation

Resource links provided by NLM:


Further study details as provided by Northwestern University:

Primary Outcome Measures:
  • Assess the incidence of biopsy-proven acute allograft rejection during the first six months of transplant [ Time Frame: At 6 months post kidney transplant ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Incidence of biopsy-proven allograft rejection during the first 9 months post-transplant [ Time Frame: At 9 months post kidney trasnplant ] [ Designated as safety issue: Yes ]
  • Severity of acute rejection during the first 6 and 12 months post-transplant
  • Renal function at 6 and 9 months post-transplant [ Time Frame: at 6 & 9 months post-transplant ] [ Designated as safety issue: Yes ]
  • Incidence of donor specific hyporesponsiveness allowing for the conversion to monotherapy [ Time Frame: at 6 & 9 months post-transplant ]
  • Patient and graft survival rates at 6 and 9 months post-transplant [ Time Frame: at 6 & 9 months post-transplant ] [ Designated as safety issue: Yes ]
  • Proportion of patients starting Mycophenolate mofetil or tacrolimus during the 12 month study period [ Time Frame: post-transplant day 7, 14, 28, week 6, 10, 14, 18, 22, month 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 ] [ Designated as safety issue: Yes ]

Enrollment: 40
Study Start Date: April 2005
Estimated Study Completion Date: October 2011
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Group 1: Alemtuzumab + Tacrolimus + Mycophenolate mofetil
Receive two doses of alemtuzumab by intravenous infusion, during kidney transplant surgery and on the 2nd day after surgery. Mycophenolate mofetil on the day of surgery and continue taking it by mouth, twice daily. Tacrolimus started on the 1st day after surgery, and then taken by mouth twice daily.
Drug: Tacrolimus
Other Name: Prograf, FK
Drug: Sirolimus
Other Name: Rapamune, Rapamycin
Drug: Alemtuzumab
Other Name: Campath
Drug: Mycophenolate mofetil
Other Name: Cellcept
Active Comparator: Group 2: Alemtuzumab + Sirolimus + Mycophenolate mofetil

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: Sirolimus
Other Name: Rapamune, Rapamycin
Drug: Alemtuzumab
Other Name: Campath
Drug: Mycophenolate mofetil
Other Name: Cellcept

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00166712

Locations
United States, Illinois
Northwestern University/Northwestern Memorial Hospital
Chicago, Illinois, United States, 60611
Sponsors and Collaborators
Northwestern University
Northwestern Memorial Hospital
Investigators
Principal Investigator: Joseph R Leventhal, MD, PhD Northwestern University
  More Information

No publications provided

Responsible Party: Josphe Leventhal, MD, Northwestern University, Northwestern Memorial Hospital, Northwestern Medical Fauculty Foundation
ClinicalTrials.gov Identifier: NCT00166712     History of Changes
Other Study ID Numbers: CEL220
Study First Received: September 9, 2005
Last Updated: September 30, 2010
Health Authority: United States: Institutional Review Board

Keywords provided by Northwestern University:
Kidney Transplant
Living Donor Kidney Transplant Recipients

Additional relevant MeSH terms:
Tacrolimus
Sirolimus
Everolimus
Mycophenolate mofetil
Mycophenolic Acid
Alemtuzumab
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 16, 2014