A Phase IV, Single Center Pilot Study Using Alemtuzumab (Campath-1H) Induction Combined With Prednisone-Free, Calcineurin-Inhibitor-Free Immunosuppression in Kidney Transplantation
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- The Incidence of Biopsy-proven Acute Allograft Rejection During the First 12 Months of Transplant.
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
- •Patients using Prednisone
- •Patients who are ABO incompatible
研究组 & 干预措施
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.
干预措施: Tacrolimus (TAC) (Drug)
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.
干预措施: Alemtuzumab (Drug)
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.
干预措施: Mycophenolate mofetil (MMF) (Drug)
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.
干预措施: Sirolimus (Drug)
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.
干预措施: Alemtuzumab (Drug)
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.
干预措施: Mycophenolate mofetil (MMF) (Drug)
结局指标
主要结局
The Incidence of Biopsy-proven Acute Allograft Rejection During the First 12 Months of Transplant.
时间窗: 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.
次要结局
- Severity of Acute Rejection During the First 6 and 12 Months Post-transplant(Months 6-12 post-transplant)
- Renal Function at 12 Months Post-transplant(At 12 months post-transplant)
- Incidence of Donor Specific Hyporesponsiveness Allowing for the Conversion to Monotherapy(At 6 & 9 months post-transplant)
- Patient and Graft Survival Rates at 6 and 12 Months Post-transplant(At 6 & 12 months post-transplant)
研究者
Joseph Leventhal
Associate Professor
Northwestern University