Targeted Therapy for High Immunologic Risk Renal Transplant Recipients: A Prospective, Randomized, Open-Label Pilot Study of B-Cell Depleting Therapy in Combination With Anti-Thymocyte Globulin [Rabbit] (Thymoglobulin®, Genzyme), Tacrolimus (Prograf®, Astellas), Mycophenolate Mofetil (CellCept®, Roche) and Corticosteroid Minimization
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 2
- 主要终点
- Incidence of Acute Rejection (Banff '97) or Antibody Mediated Rejection
研究概览
简要总结
The purpose of this research study is to find out the effects of adding B lymphocyte modulating agents in patients at risk for rejection receiving an anti-rejection (immunosuppressive) regimen of Thymoglobulin® induction with Prograf®, Cellcept® and corticosteroid therapy.
详细描述
Optimal induction regimens for patients at high risk for antibody and/or cell-mediated rejection have not been established. This pilot, prospective, randomized study evaluated addition of B cell/plasma cell-targeting agents to T cell-based induction with rabbit antithymocyte globulin (rATG) in high immunologic risk renal transplant recipients. Patients were randomized to induction with rATG, rATGþrituximab, rATGþbortezomib or rATGþrituximabþbortezomib.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Rabbit Antithymocyte Globulin (rATG)
Rabbit Antithymocyte Globulin (rATG) 1.5mg/kg per dose x 6 doses rATG was administered on post-op day 0, 2, 4, 6, 8 and 10.
干预措施: Rabbit Antithymocyte Globulin (Drug)
RATG/Rituxan
Rabbit Antithymocyte Globulin (rATG)/Rituxan 1.5mg/kg per dose x 5 doses of rATG. 375mg/m2 x 1 dose of rituxan. rATG was administered on post-op day 0, 2, 4, 6 and 8. Rituxan was given on post-op day 1.
干预措施: Rabbit Antithymocyte Globulin (Drug)
RATG/Rituxan
Rabbit Antithymocyte Globulin (rATG)/Rituxan 1.5mg/kg per dose x 5 doses of rATG. 375mg/m2 x 1 dose of rituxan. rATG was administered on post-op day 0, 2, 4, 6 and 8. Rituxan was given on post-op day 1.
干预措施: Rituxan (Drug)
RATG/Velcade
Rabbit Antithymocyte Globulin (rATG) /Velcade 1.5mg/kg per dose x 5 doses of rATG. 1.3mg/m2 per dose x 4 doses of velcade. rATG was administered on post-op day 0, 2, 4, and 6. Velcade was administered on post-op day 0, 3, 7 and 10.
干预措施: Rabbit Antithymocyte Globulin (Drug)
RATG/Velcade
Rabbit Antithymocyte Globulin (rATG) /Velcade 1.5mg/kg per dose x 5 doses of rATG. 1.3mg/m2 per dose x 4 doses of velcade. rATG was administered on post-op day 0, 2, 4, and 6. Velcade was administered on post-op day 0, 3, 7 and 10.
干预措施: Velcade (Drug)
RATG/Rituxan/Velcade
Rabbit Antithymocyte Globulin (RATG) / Rituxan / Velcade 1.5mg/kg per dose x 4 doses of rATG. 200mg/m2 for 1 dose of rituxan. 1.3mg/m2 per dose x 4 doses of velcade.
rATG was administered on post-op day 0, 2, 4, and 6. Velcade was administered on post-op day 0, 3, 7 and 10. Rituxan was given on post-op day 1.
干预措施: Rabbit Antithymocyte Globulin (Drug)
RATG/Rituxan/Velcade
Rabbit Antithymocyte Globulin (RATG) / Rituxan / Velcade 1.5mg/kg per dose x 4 doses of rATG. 200mg/m2 for 1 dose of rituxan. 1.3mg/m2 per dose x 4 doses of velcade.
rATG was administered on post-op day 0, 2, 4, and 6. Velcade was administered on post-op day 0, 3, 7 and 10. Rituxan was given on post-op day 1.
干预措施: Velcade (Drug)
RATG/Rituxan/Velcade
Rabbit Antithymocyte Globulin (RATG) / Rituxan / Velcade 1.5mg/kg per dose x 4 doses of rATG. 200mg/m2 for 1 dose of rituxan. 1.3mg/m2 per dose x 4 doses of velcade.
rATG was administered on post-op day 0, 2, 4, and 6. Velcade was administered on post-op day 0, 3, 7 and 10. Rituxan was given on post-op day 1.
干预措施: Rituxan (Drug)
结局指标
主要结局
Incidence of Acute Rejection (Banff '97) or Antibody Mediated Rejection
时间窗: 6 months
Antibody mediated rejection demonstrated to be due to, atleast in part, to anti-donor antibody at 6 months by Banff 97' criteria. Acute rejection IA - cases with significant interstitial infiltration (\>25% of parenchyma affected) and foci of moderate tubulitis (\>4 mononuclear cells/tubular cross section or group of 10 tubular cells). IB - cases with significant interstitial infiltration (\>25% of parenchyma affected) and foci of severe tubulitis (\>10 mononuclear cells/tubular cross section or group of 10 tubular cells) IIA - cases with mild to moderate intimal arteritis (v1) IIB - cases with server intimal arteritis comprising \>25% of the luminal area (v2) III - case with transmural arteritis and/or arterial fibrinoid change and necrosis of medical smooth muscle cells (v3 with accompanying lymphoctic inflammation)
次要结局
- Acute Cellular Rejection by Banff '97 Criteria (Updated 2005)(6 months)
- Patient Allograft Survival at 12 Months(12 months)
- Antibody-mediated Rejection by Banff '97 Criteria (Updated 2005)(6 months)
- Patient Survival at 12 Months(12 months)
研究者
E. Steve Woodle
MD, FACS
University of Cincinnati