Phase I Feasibility Study of Clofarabine and Low Dose Total Body Irradiation (TBI) as a Non-myeloablative Preparative Regimen for Stem Cell Transplantation (SCT) for Hematologic Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 18
- 试验地点
- 6
- 主要终点
- Maximum Feasible Dose of Clofarabine
研究概览
简要总结
Stem cell transplant is an important therapeutic option for pediatric patients with relapsed or refractory leukemia. Although, full myeloablative transplants are widely used for patients with acute leukemia, myeloablative chemo-radiotherapy may not be feasible in some specific settings. These settings include 1) patients with pre-existing health issues and organ toxicities; 2) patients who have relapsed post-ablative transplant and need a second stem cell transplant; and 3) leukemia patients with advanced disease who have been heavily pre-treated. Clofarabine, a new purine nucleoside anti-metabolite, has the advantage of significant antileukemic activity in addition to its possible immuno-suppressive properties. In this study we plan to determine the maximum feasible dose (MFD) of Clofarabine in combination with total body irradiation that can achieve durable donor engraftment without causing excessive toxicity.
详细描述
Standard non-myeloablative regimens use Fludarabine and low dose total body irradiation (TBI) as pioneered by the Seattle group. Fludarabine is mainly used for its immuno-suppressive properties and has limited anti-leukemic effects. Since, the non-myeloablative and RIC regimens do not include intensive chemotherapy; relapse rates can be higher in RIC regimens compared to full myeloablative regimens. One way to improve overall survival in non-myeloablative / RIC setting is to add more effective anti-leukemia agents to prevent post-transplant relapses, without increasing TRM. Clofarabine, a new purine nucleoside anti-metabolite, has the advantage of significant antileukemic activity in addition to its possible immuno-suppressive properties. Combining Clofarabine with low dose TBI as a non-myeloablative preparative regimen may improve overall outcomes of SCT in advanced hematological malignancies. Therefore, in this study we plan to determine the maximum feasible dose (MFD) of Clofarabine in combination with 2Gy TBI that can achieve durable donor engraftment without causing excessive toxicity. The MFD determined from this pilot will be used in the next phase to study the outcomes after using this combination for SCT in this very high risk population.
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
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Year 至 21 Years（Child, 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
Related Donor Arm
Patients with related stem cell donors. Patients will receive Clofarabine in combination with 2Gy total body irradiation (TBI) as a preparative regimen for stem cell transplantation, in turn followed by cyclosporine and Mycophenolate Mofetil as GVHD prophylaxis.
干预措施: Clofarabine (Drug)
Related Donor Arm
Patients with related stem cell donors. Patients will receive Clofarabine in combination with 2Gy total body irradiation (TBI) as a preparative regimen for stem cell transplantation, in turn followed by cyclosporine and Mycophenolate Mofetil as GVHD prophylaxis.
干预措施: Total Body Irradiation (Radiation)
Related Donor Arm
Patients with related stem cell donors. Patients will receive Clofarabine in combination with 2Gy total body irradiation (TBI) as a preparative regimen for stem cell transplantation, in turn followed by cyclosporine and Mycophenolate Mofetil as GVHD prophylaxis.
干预措施: Stem Cell Transplantation (Other)
Related Donor Arm
Patients with related stem cell donors. Patients will receive Clofarabine in combination with 2Gy total body irradiation (TBI) as a preparative regimen for stem cell transplantation, in turn followed by cyclosporine and Mycophenolate Mofetil as GVHD prophylaxis.
干预措施: Cyclosporine (Drug)
Related Donor Arm
Patients with related stem cell donors. Patients will receive Clofarabine in combination with 2Gy total body irradiation (TBI) as a preparative regimen for stem cell transplantation, in turn followed by cyclosporine and Mycophenolate Mofetil as GVHD prophylaxis.
干预措施: Mycophenolate Mofetil (Drug)
Unrelated Donor Arm
Patients with unrelated stem cell donors. Patients will receive Clofarabine in combination with 2Gy total body irradiation (TBI) as a preparative regimen for stem cell transplantation, in turn followed by cyclosporine and Mycophenolate Mofetil as GVHD prophylaxis.
干预措施: Clofarabine (Drug)
Unrelated Donor Arm
Patients with unrelated stem cell donors. Patients will receive Clofarabine in combination with 2Gy total body irradiation (TBI) as a preparative regimen for stem cell transplantation, in turn followed by cyclosporine and Mycophenolate Mofetil as GVHD prophylaxis.
干预措施: Total Body Irradiation (Radiation)
Unrelated Donor Arm
Patients with unrelated stem cell donors. Patients will receive Clofarabine in combination with 2Gy total body irradiation (TBI) as a preparative regimen for stem cell transplantation, in turn followed by cyclosporine and Mycophenolate Mofetil as GVHD prophylaxis.
干预措施: Stem Cell Transplantation (Other)
Unrelated Donor Arm
Patients with unrelated stem cell donors. Patients will receive Clofarabine in combination with 2Gy total body irradiation (TBI) as a preparative regimen for stem cell transplantation, in turn followed by cyclosporine and Mycophenolate Mofetil as GVHD prophylaxis.
干预措施: Cyclosporine (Drug)
Unrelated Donor Arm
Patients with unrelated stem cell donors. Patients will receive Clofarabine in combination with 2Gy total body irradiation (TBI) as a preparative regimen for stem cell transplantation, in turn followed by cyclosporine and Mycophenolate Mofetil as GVHD prophylaxis.
干预措施: Mycophenolate Mofetil (Drug)
结局指标
主要结局
Maximum Feasible Dose of Clofarabine
时间窗: Day +100
The primary objective of the study is to determine the maximum feasible dose (MFD) of Clofarabine that can be given in combination with 2Gy total body irradiation as a non-myeloablative preparative regimen for allogeneic stem cell transplantation in pediatric patients with relapsed leukemia. The MFD is defined as the highest clofarabine dose associated with both an acceptably low toxicity and low non-engraftment (NE) rate. NE is defined as \< 5% donor T cells at any time point during serial monitoring. Monitoring during the evaluation period is required Day +30, +60 and +100.
次要结局
- Days of Engraftment in Both Matched Related Donor (MRD) and Matched Unrelated Donor (MUD)(Days +30, 60, 100, 180)
- Transplant Related Mortality (TRM) at Day +100(Day 100)
- Days to Platelet Recovery(Days +30, 60, 100, 180)