A Trial of Two Steroid-Free Approaches Toward Mycophenolate Mofetil-Based Monotherapy Immunosuppression
Recruitment status was Active, not recruiting
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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 |
- 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 ]
- 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 |
Inclusion Criteria:
- Patients who are male or female age 18-65 years
- Donor age 18-65 years
- Patients who are single-organ recipients (kidney only)
- 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.
- Subject (recipient) is able to understand the consent form and give written informed consent
Exclusion Criteria:
- Known sensitivity or contraindication to sirolimus, tacrolimus or MMF
- Patient with significant or active infection
- Patients with a positive lymphocytotoxic crossmatch using donor lymphocytes and recipient serum
- Patients with PRA > 20%
- Patients who are pregnant or nursing mothers
- Patients whose life expectancy is severely limited by diseases other than renal disease
- Ongoing active substance abuse, drug or alcohol
- Major ongoing psychiatric illness or recent history of noncompliance
Significant cardiovascular disease (e.g.):
- Significant non-correctable coronary artery disease
- Ejection fraction below 30%
- History of recent myocardial infarction
- Malignancy within 3 years, excluding non-melanoma skin cancers
- Serologic evidence of infection with HIV or HBVsAg positive
- 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
- Investigational drug within 30 days prior to transplant surgery
- Anti-T cell therapy within 30 days prior to transplant surgery
Contacts and Locations| United States, Illinois | |
| Northwestern University/Northwestern Memorial Hospital | |
| Chicago, Illinois, United States, 60611 | |
| 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:
|
Mycophenolate mofetil Sirolimus Everolimus Tacrolimus Campath 1G Antibodies, Neoplasm Mycophenolic Acid Alemtuzumab Immunosuppressive Agents Immunologic Factors |
Physiological Effects of Drugs Pharmacologic Actions Antibiotics, Antineoplastic Antineoplastic Agents Therapeutic Uses Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antifungal Agents Anti-Infective Agents Anti-Bacterial Agents |
ClinicalTrials.gov processed this record on May 16, 2013