Sirolimus, Mycophenolate Mofetil and Bortezomib as Graft-Versus-Host Disease Prophylaxis After Non-Myeloablative Allogeneic Peripheral Blood Stem Cell Transplantation
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- To Determine the Rate of Grade II-IV Acute GVHD When Sirolimus and Mycophenolate Mofetil or Sirolimus, Mycophenolate Mofetil and Bortezomib is Used for GVHD Prophylaxis After Allogeneic Stem Cell Transplantation in Patients With Hematologic Malignancies
研究概览
简要总结
This trial will test the hypothesis that the combination of sirolimus, mycophenolate mofetil, and bortezomib will be effective in preventing both acute and chronic GVHD after reduced intensity allogeneic stem cell transplantation.
详细描述
The combination of tacrolimus and methotrexate is standard therapy for prevention of GVHD, however, our recent experience has demonstrated that the substitution of sirolimus for methotrexate provides superior GVHD control with reduced transplant-related toxicity. One limitation to the use of calcineurin inhibitors in GVHD prevention is the disruption in Treg function and proliferation. Based on our evolving understanding of the role of Treg in the development of chronic GVHD, we propose a GVHD prophylactic regimen that is effective in prevention of acute GVHD, but by virtue of the maintenance of Treg activity may be able to prevent chronic GVHD. We hypothesize that the substitution of mycophenolate mofetil for tacrolimus as well as the addition of bortezomib may provide similar protection against acute GVHD and prevent chronic GVHD while minimizing renal toxicity after transplantation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with hematologic malignancies, who are at high risk of complications after conventional myeloablative transplantation
- •Patients must have a 6/6 matched, related donor. Matching at HLA Class II will be based on PCR of sequence specific primers (SSP). Among family member transplants, serologic matching at Class I is sufficient
- •Patient age greater than 18
- •Performance status 0-2
- •Life expectancy of > 100 days without transplantation
- •Written informed consent must be obtained in all cases from the patient
排除标准
- •Prior Allogeneic Stem Cell Transplantation from any donor
- •Evidence of HIV infection or active Hepatitis B or C infection
- •Heart failure uncontrolled by medications
- •Total bilirubin > 2.0 mg/dl that is due to hepatocellular dysfunction
- •Cholesterol > 300 mg/dl or Triglycerides > 400 mg/dl while adequately treated
- •Uncontrolled bacterial, viral or fungal infection
- •Requirement for voriconazole at the time of hospital admission
研究组 & 干预措施
Siro/MMF
Sirolimus and Mycophenolate Mofetil as GVHD Prophylaxis Sirolimus (Rapamycin); Mycophenolate Mofetil (MMF)
干预措施: Sirolimus (Drug)
Siro/MMF
Sirolimus and Mycophenolate Mofetil as GVHD Prophylaxis Sirolimus (Rapamycin); Mycophenolate Mofetil (MMF)
干预措施: Mycophenolate mofetil (Drug)
Siro/MMF/Bort
Sirolimus, Mycophenolate Mofetil, and Bortezomib as GVHD Prophylaxis Sirolimus (Rapamycin); Mycophenolate Mofetil (MMF) Bortezomib (Velcade) *added with study reopening in 2012
干预措施: Sirolimus (Drug)
Siro/MMF/Bort
Sirolimus, Mycophenolate Mofetil, and Bortezomib as GVHD Prophylaxis Sirolimus (Rapamycin); Mycophenolate Mofetil (MMF) Bortezomib (Velcade) *added with study reopening in 2012
干预措施: Mycophenolate mofetil (Drug)
Siro/MMF/Bort
Sirolimus, Mycophenolate Mofetil, and Bortezomib as GVHD Prophylaxis Sirolimus (Rapamycin); Mycophenolate Mofetil (MMF) Bortezomib (Velcade) *added with study reopening in 2012
干预措施: Bortezomib (Drug)
结局指标
主要结局
To Determine the Rate of Grade II-IV Acute GVHD When Sirolimus and Mycophenolate Mofetil or Sirolimus, Mycophenolate Mofetil and Bortezomib is Used for GVHD Prophylaxis After Allogeneic Stem Cell Transplantation in Patients With Hematologic Malignancies
时间窗: 150 days
次要结局
- Overall Survival(1 year)
- Donor Stem Cell Engraftment, Including Donor-host Hematopoietic Chimerism Studies Post Transplant(30 days)
- The Rate of Renal Insufficiency(1 year)
- Incidence of 100 Day Mortality(100 days)
- To Correlate the Serum Concentrations of Mycophenolate Mofetil and Its Metabolites With Acute GVHD Incidence(1 year)
- Incidence of Chronic GVHD(1 year)
研究者
Corey S. Cutler, MD, MPH
Principal Investigator
Dana-Farber Cancer Institute