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

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.

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