Phase I/II Study of Intravenous (IV) Busulfan and Etoposide (VP-16) Combined With Escalated Doses of Large Field Image-Guided Intensity Modulated Radiation Therapy (IMRT) Using Helical Tomotherapy as a Preparative Regimen for Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) for Patients With Advanced Myeloid Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD) of Intensity-modulated Radiation Therapy (Phase I)
研究概览
简要总结
RATIONALE: Giving chemotherapy drugs, such as busulfan and etoposide, and intensity-modulated radiation therapy before a donor stem cell transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving intensity-modulated radiation therapy together with busulfan and etoposide before a transplant may stop this from happening.
PURPOSE: This phase I/II trial is studying the side effects and best dose of intensity-modulated radiation therapy when given together with busulfan and etoposide followed by a donor stem cell transplant and to see how well it works in treating patients with advanced myeloid cancer.
详细描述
OBJECTIVES:
I. To establish the maximum tolerated dose (MTD) of a large field image-guided IMRT, using helical tomotherapy, when given in combination with IV busulfan and VP-16 as a preparative regimen for allogeneic hematopoietic stem cell transplantation (HSCT) from an HLA-identical sibling in patients with advanced myeloid malignancies. (Phase I) II. To describe the toxicities at each dose level studied. (Phase I) III. To estimate the radiation doses to the whole body, normal organs, and bone marrow through serial imaging studies following the administration of IMRT. (Phase I) IV. To estimate the overall survival probability, disease-free survival probability, and relapse rate associated with this preparative regimen. (Phase II) V. To characterize the treatment related mortality and toxicity profile (early/late) associated with this regimen. (Phase II) VI. To descriptively compare the outcomes of patients treated on this protocol to a comparable patient population conditioned with whole-body radiotherapy. (Phase II)
OUTLINE: This is a phase I, dose-escalation study of intensity-modulated radiation therapy followed by a phase II study.
PREPARATIVE CHEMOTHERAPY: Patients receive busulfan IV once daily over 2 hours on days -15 and -13 and then every 6 hours on days -12 to -9. Patients also receive etoposide IV on day -3. Patients undergo image-guided intensity-modulated radiation therapy using helical tomotherapy on days -8 to -5.
TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation or bone marrow transplantation on day 0.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 6 Years 至 55 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
Arm I: 1200cGy
1200cGy = 150cGy x 8 doses: Patients receive busulfan IV once daily over 2 hours on days -15 and -13 and then every 6 hours on days -12 to -9. Patients also receive etoposide IV on day -3. Patients undergo image-guided intensity-modulated radiation therapy using helical tomotherapy on days -8 to -5.
TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation or bone marrow transplantation on day 0.
GRAFT-VS-HOST DISEASE (GVHD) PROPHYLAXIS: Patients receive GVHD prophylaxis that excludes methotrexate.
干预措施: busulfan (Drug)
Arm I: 1200cGy
1200cGy = 150cGy x 8 doses: Patients receive busulfan IV once daily over 2 hours on days -15 and -13 and then every 6 hours on days -12 to -9. Patients also receive etoposide IV on day -3. Patients undergo image-guided intensity-modulated radiation therapy using helical tomotherapy on days -8 to -5.
TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation or bone marrow transplantation on day 0.
GRAFT-VS-HOST DISEASE (GVHD) PROPHYLAXIS: Patients receive GVHD prophylaxis that excludes methotrexate.
干预措施: etoposide (Drug)
Arm I: 1200cGy
1200cGy = 150cGy x 8 doses: Patients receive busulfan IV once daily over 2 hours on days -15 and -13 and then every 6 hours on days -12 to -9. Patients also receive etoposide IV on day -3. Patients undergo image-guided intensity-modulated radiation therapy using helical tomotherapy on days -8 to -5.
TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation or bone marrow transplantation on day 0.
GRAFT-VS-HOST DISEASE (GVHD) PROPHYLAXIS: Patients receive GVHD prophylaxis that excludes methotrexate.
干预措施: intensity-modulated radiation therapy (Radiation)
Arm I: 1200cGy
1200cGy = 150cGy x 8 doses: Patients receive busulfan IV once daily over 2 hours on days -15 and -13 and then every 6 hours on days -12 to -9. Patients also receive etoposide IV on day -3. Patients undergo image-guided intensity-modulated radiation therapy using helical tomotherapy on days -8 to -5.
TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation or bone marrow transplantation on day 0.
GRAFT-VS-HOST DISEASE (GVHD) PROPHYLAXIS: Patients receive GVHD prophylaxis that excludes methotrexate.
干预措施: allogeneic hematopoietic stem cell transplantation (Procedure)
Arm I: 1200cGy
1200cGy = 150cGy x 8 doses: Patients receive busulfan IV once daily over 2 hours on days -15 and -13 and then every 6 hours on days -12 to -9. Patients also receive etoposide IV on day -3. Patients undergo image-guided intensity-modulated radiation therapy using helical tomotherapy on days -8 to -5.
TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation or bone marrow transplantation on day 0.
GRAFT-VS-HOST DISEASE (GVHD) PROPHYLAXIS: Patients receive GVHD prophylaxis that excludes methotrexate.
干预措施: allogeneic bone marrow transplantation (Procedure)
Arm I: 1200cGy
1200cGy = 150cGy x 8 doses: Patients receive busulfan IV once daily over 2 hours on days -15 and -13 and then every 6 hours on days -12 to -9. Patients also receive etoposide IV on day -3. Patients undergo image-guided intensity-modulated radiation therapy using helical tomotherapy on days -8 to -5.
TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation or bone marrow transplantation on day 0.
GRAFT-VS-HOST DISEASE (GVHD) PROPHYLAXIS: Patients receive GVHD prophylaxis that excludes methotrexate.
干预措施: peripheral blood stem cell transplantation (Procedure)
Arm I: 1200cGy
1200cGy = 150cGy x 8 doses: Patients receive busulfan IV once daily over 2 hours on days -15 and -13 and then every 6 hours on days -12 to -9. Patients also receive etoposide IV on day -3. Patients undergo image-guided intensity-modulated radiation therapy using helical tomotherapy on days -8 to -5.
TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation or bone marrow transplantation on day 0.
GRAFT-VS-HOST DISEASE (GVHD) PROPHYLAXIS: Patients receive GVHD prophylaxis that excludes methotrexate.
干预措施: tomotherapy (Radiation)
Arm II: 1350cGy
1350cGy = 150cGy x 9 doses: Patients receive busulfan IV once daily over 2 hours on days -15 and -13 and then every 6 hours on days -12 to -9. Patients also receive etoposide IV on day -3. Patients undergo image-guided intensity-modulated radiation therapy using helical tomotherapy on days -8 to -5.
干预措施: busulfan (Drug)
Arm II: 1350cGy
1350cGy = 150cGy x 9 doses: Patients receive busulfan IV once daily over 2 hours on days -15 and -13 and then every 6 hours on days -12 to -9. Patients also receive etoposide IV on day -3. Patients undergo image-guided intensity-modulated radiation therapy using helical tomotherapy on days -8 to -5.
干预措施: etoposide (Drug)
Arm II: 1350cGy
1350cGy = 150cGy x 9 doses: Patients receive busulfan IV once daily over 2 hours on days -15 and -13 and then every 6 hours on days -12 to -9. Patients also receive etoposide IV on day -3. Patients undergo image-guided intensity-modulated radiation therapy using helical tomotherapy on days -8 to -5.
干预措施: intensity-modulated radiation therapy (Radiation)
Arm II: 1350cGy
1350cGy = 150cGy x 9 doses: Patients receive busulfan IV once daily over 2 hours on days -15 and -13 and then every 6 hours on days -12 to -9. Patients also receive etoposide IV on day -3. Patients undergo image-guided intensity-modulated radiation therapy using helical tomotherapy on days -8 to -5.
干预措施: allogeneic hematopoietic stem cell transplantation (Procedure)
Arm II: 1350cGy
1350cGy = 150cGy x 9 doses: Patients receive busulfan IV once daily over 2 hours on days -15 and -13 and then every 6 hours on days -12 to -9. Patients also receive etoposide IV on day -3. Patients undergo image-guided intensity-modulated radiation therapy using helical tomotherapy on days -8 to -5.
干预措施: allogeneic bone marrow transplantation (Procedure)
Arm II: 1350cGy
1350cGy = 150cGy x 9 doses: Patients receive busulfan IV once daily over 2 hours on days -15 and -13 and then every 6 hours on days -12 to -9. Patients also receive etoposide IV on day -3. Patients undergo image-guided intensity-modulated radiation therapy using helical tomotherapy on days -8 to -5.
干预措施: peripheral blood stem cell transplantation (Procedure)
Arm II: 1350cGy
1350cGy = 150cGy x 9 doses: Patients receive busulfan IV once daily over 2 hours on days -15 and -13 and then every 6 hours on days -12 to -9. Patients also receive etoposide IV on day -3. Patients undergo image-guided intensity-modulated radiation therapy using helical tomotherapy on days -8 to -5.
干预措施: tomotherapy (Radiation)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of Intensity-modulated Radiation Therapy (Phase I)
时间窗: from initial treatment date to Day 30 post-transplant
The highest dose tested in which fewer than 33% of patients experienced DLT attributable to the study treatment when at least six patients were treated at the dose and are evaluable for toxicity. The MDT is one dose level below the DLT level. At least six patients will be treated at the MTD.
次要结局
未报告次要终点