Extended Dose - Total Body Irradiation Followed By Allogeneic Stem Cell Transplantation For The Treatment Of Refractory Acute Leukemia And Advanced Myelodysplastic Syndrome
试验速览
- 阶段
- 2 期
- 状态
- 暂停
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Progression-free survival
研究概览
简要总结
Acute myeloid leukemia (AML) is a rapidly fatal malignancy of the bone marrow. It can be treated with chemotherapy alone, in some cases, but in the majority of cases, the only treatment that can cure the disease is an allogeneic stem cell transplant, with a cure rate of 30-40%. In another subset, the disease is less responsive to chemotherapy and in these aggressive forms, its cure rate is no better than 20% beyond 2 years, and is usually rapidly fatal within 6 months.
Therefore, for this most aggressive form of the disease, modifications to the transplant protocol are required in order to try to improve on these poor results. There are a number of areas within the transplant protocol on which modifications can be made in order to achieve these goals. These include: higher doses of chemotherapy and or radiation; alterations of the new bone marrow graft; and alterations of the immune suppression, enhancing the graft vs. leukemia effect. By focusing on one or more of these components, one might be able to enhance the anti-leukemic aspect of the treatment resulting in a more successful outcome.
One aspect the investigators, in Ottawa, have focused on is the initial intensive conditioning regimen, specifically the radiation component. It is the investigators belief that in the most resistant disease it is important to use the highest tolerable anti-leukemic treatment upfront, specifically, enhancing the radiation component of the initial conditioning regimen. Previous studies have suggested that higher doses of radiation might be more effective at eliminating the disease, however, toxicity and logistics of delivering the radiation have limited its use. Technical advances in the delivery of radiation have now permitted the safer use of high doses of radiation.
Through modifications to the transplant procedure, the investigators believe that they can deliver higher doses of radiation safely and this will translate into improved outcomes in this high-risk subgroup of patients with AML.
Study Objectives
The goal of this study is to determine if a total dose of 18Gy ED-TBI followed by an alloHSCT for patients with refractory AML will result in an improved progression-free survival.
详细描述
Study Rationale
- AML is a bone marrow based malignancy that is rapidly growing and rapidly fatal if left untreated. Despite therapeutic strategies for up to 70% of patients, 20% are primarily refractory and another 50% will relapse after first line therapy. Among these refractory and relapsed patients the only, potentially, effective therapy is an alloHSCT, however, long-term survival rates range from as low as <10% up to 20%.
- Increased doses of radiation in the form of TBI to a threshold of 15.75 Gy with chemotherapy have been demonstrated to reduce the relapse rate significantly; however, OS is compromised by the high rate of toxicity.
- Evidence suggests that escalated doses of radiation are possible, which offers the potential to increase the dose of radiation to as much as 20Gy, safely.
- Locally, increased doses of radiation without chemotherapy did not demonstrate any significant toxicity up to a dose of 16Gy.
- Therefore, as proposed a radiation-only stem cell transplant would allow us to test the hypothesis that increased doses of radiation will reduce the relapse rate while minimizing the toxicity in a very high-risk population of patients with AML, resulting in an improved progression-free and overall survival.
Trial Design
This is a single institution, Phase II study examining the efficacy and toxicity of ED-TBI followed by an alloHSCT on patients with high risk, refractory acute myeloid leukemia.
Treatment Overview
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（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
结局指标
主要结局
Progression-free survival
时间窗: 1 year post allogenic transplant
The primary objective of this study is to determine the progression-free survival at 1 year, post alloHSCT, after ED-TBI followed by an alloHSCT for patients with refractory AML
次要结局
- Engraftment(Within 100 day post transplant)
- Relapse(5 years post transplant)
- Morbidity/Mortality(day 30, day 100, day 180 post transplant)
- GVHD(day 30, day 100, 180, 365 and 730 post transplant)