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
- 1
- 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
- •All subjects must meet all of the following criteria to be eligible for the study. These will be evaluated within the four weeks prior to enrolment.
- •Subject must have primary refractory AML, secondary AML, relapsed AML or high risk MDS
- •Primary refractory AML is defined as:
- •A blast count in the bone marrow of >5% or the presence of any amount of circulating blasts, in the peripheral blood, after 1 cycle of induction chemotherapy.
- •Secondary AML is defined as:
- •AML, except acute promyelocytic leukemia, arising from any haematological disease or from the exposure to chemotherapy for another unrelated malignancy.
- •Relapsed AML is defined as:
- •Relapse (>5% blasts in the marrow) after having achieved a CR, of any duration.
- •High risk myelodysplasia is defined as:
- •Myelodysplastic syndrome as defined by the WHO criteria with an international prognostic score (IPSS) of intermediate-2 or high
- •Subjects must have a score of ≥2 on the scoring system for hematopoietic stem-cell transplantation for acute leukemia in relapse or primary induction failure
- •Subjects must meet institutional guidelines for an alloHSCT.
- •Subjects must have a matched related or a well- or partially-matched unrelated donor, acceptable to institutional guidelines who can donate either peripheral blood or bone marrow hematopoietic stem cells.
- •Subjects must be of age ≥18 and ≤60 years.
- •Subjects must have an ECOG performance score of 0,1, or 2
- •Subjects must have the ability to comply with the protocol visit schedule and other protocol requirements.
排除标准
- •Subjects who have a score of < 2 on the scoring system for hematopoietic stem-cell transplantation for acute leukemia in relapse or primary induction failure
- •Subjects who previously received an autoHSCT or alloHSCT
- •Subjects who have previously received radiation therapy
- •Subjects with a prior nephrectomy or a known history of a single kidney.
- •Subjects with HIV-seropositivity.
- •Subjects with a recent history of alcohol or drug abuse.
- •Pregnant or lactating female subjects.
- •Subject whose only donor is an umbilical cord donor
- •Subjects whose only donor is an unrelated mismatched donor, according the recently published CIBMTR criteria.
研究组 & 干预措施
18 cGY ED-TBI
18 cGY ED-TBI followed by an allogenic done marrow transplant
干预措施: ED-TBI (Radiation)
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)