Randomized Clinical Study of Haplo-Identical Donors Versus Unrelated Donors in Hematopoietic Stem Cell Transplant Patients With Acute Myeloid Leukemia
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 18
- 试验地点
- 18
- 主要终点
- Intention to treat analysis of 2-year graft-vs.-host disease- and relapse-free survival
研究概览
简要总结
This study compares haplo-identical family donor stem cell transplantation (haplo SCT) to matched unrelated donor transplantation (URD SCT) in adult patients with acute myeloid leukemia (AML) with the hypothesis that haplo SCT is as good as URD SCT.
Background:
A haplo-identical family donor is a relative sharing 50% of the human leukocyte antigens (HLA) of the patient. SCT with this type of donor is increasing, and a number of retrospective studies have demonstrated its feasibility, but prospective randomized studies are still lacking. Such studies are necessary to establish the benefits of haplo SCT. For the ≈70% of the patients that lack the 1st choice donor, an HLA-matched sibling, the 2nd choice is an URD at most centers. However, if haplo-identical donors are as good as URDs, this could change. Haplo-identical donors have several advantages. Almost all patients have at least one available haplo-identical donor, while URDs can be difficult to find. It also eliminates the need for time-consuming donor searches, and is considerably less costly.
The Study:
Patients can be included in the study if they have AML and require SCT, ≥18 years, DO NOT have an HLA-matched sibling donor, and DO have potential haplo-identical family donors AND URDs.
After enrollment in the study, the patients are assigned randomly to either haplo SCT or URD SCT. The treatment surrounding the transplantation differs according to the donor type. Patients receiving haplo-identical transplantation are treated with a specified chemotherapy protocol before transplantation and a chemotherapy combined with immunosuppressive drugs after the transplantation to prevent graft-vs. host disease (GVHD). The patients receiving URD SCT will be treated according to the standard protocol at their center. Thus, haplo SCT will be compared to what is currently used in patients without an HLA-identical sibling today.
The primary endpoint of this study is graft-vs.-host disease- and relapse free survival two years after study inclusion. This measurement takes into account the side effect that causes the most long-term suffering, graft-vs-host disease, as well as leukemia relapse and thus indicates to what extent the treated patients remain relapse-free and without significant side effects. Secondary end points include relapse-free survival, frequencies of graft-versus-host disease and of infections, and the patients will be followed in the study for five years.
详细描述
This is a randomized, intention-to-treat, open label, non-inferiority study performed in an international multicenter setting comparing allogeneic stem cell transplantation (SCT) with haplo-identical family donors (haplo SCT) to matched unrelated donor (URD) SCT in adult patients with de novo or treatment related acute myeloid leukemia (AML). The primary study objective is to compare GVHD and relapse free survival (GRFS) at 2 years post-randomization in patients randomized to Haplo-SCT with patients randomized to URD-SCT.
The choice of hematopoietic stem cell donor, the humal leukocyte antigen (HLA) match, and the type of graft used are factors of major importance for survival and the risk of complications after SCT. The use of haplo-identical donors has shown very promising results and may result in a paradigm shift in SCT. However, no prospective randomized studies comparing unrelated donors, the standard choice today when no HLA-identical sibling is available, with haplo-identical donors have been published. The purpose of this study is to evaluate in a prospective and randomised fashion whether haplo-identical donor SCT could yield similar results to SCT with unrelated donors in patients with AML.
HYPOTHESIS:
The graft-vs.-host disease- and relapse-free survival two years after randomization (2-year GRFS) after haplo SCT is not inferior to 2-year GRFS after URD SCT with donors matched at 7/8 or 8/8 of the major HLA loci.
STUDY POPULATION
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 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
- •Adult patients (age ≥ 18 years) with de novo or treatment-related AML, eligible and fit for SCT treatment according to national/international guidelines.
- •One or more potential haplo-identical related donor(s) AND five or more potential 6/6 HLA-A, -B, and -DRB1 antigen matched unrelated donors identified before randomization.
- •Karnofsky Performance Status ≥ 70% at randomization.
- •Signed informed consent.
- •Patient willing and able to comply with protocol requirements
排除标准
- •Patients with a suitable HLA-identical sibling donor.
- •Patients with < 5 potential HLA-A, -B, and -DRB1 antigen matched URDs available.
- •Patients with no potential haplo-identical related donor available.
- •Patients scheduled for/receiving cord blood stem cell transplantation.
- •Prior allogeneic SCT using any hematopoietic stem cell source.
- •Patients seropositive for HIV.
- •Pregnancy (positive β-HCG test) within 4 weeks of study entry.
- •Cardiac ejection fraction < 45%.
- •Karnofsky Performance Status < 70% at time of randomization.
- •The presence of any psychological, family-related, social, and/or geographical condition potentially jeopardizing compliance with the study protocol and follow-up schedule.
结局指标
主要结局
Intention to treat analysis of 2-year graft-vs.-host disease- and relapse-free survival
时间窗: 2 years
Defined in this study as the time between inclusion and either grades III-IV acute GVHD, severe chronic GVHD or disease relapse. All events occuring from SCT to last follow-up are considered when calculating GRFS. Incomplete data resulting from patients who are lost to follow-up or who withdraw their informed consent will be censored at the date they were last known to be alive. Patients who are alive at study termination will be censored at the latest date of contact. Analysed according to original treatment arm assignment (intention-to-treat)
次要结局
- Per protocol analysis of 2-year graft-vs.-host disease- and relapse-free survival(2 years)
- Per protocol analysis of Overall survival(2 years and 5 years)
- Per protocol analysis of Disease-free survival(2 years and 5 years)
- Infection(2 years)
- Secondary malignancies(5 years)
- Intention to treat analysis of 5-year graft-vs.-host disease- and relapse-free survival(5 years)
- Per protocol analysis of 5-year graft-vs.-host disease- and relapse-free survival(5 years)
- Intention to treat analysis of Overall survival(2 years and 5 years)
- Intention to treat analysis of Disease-free survival(2 years and 5 years)
- Acute graft.vs.-host disease(2 years)
- Chronic graft.vs.-host disease(2 years and 5 years)
- Relapse(2 years and 5 years)
- Engraftment of neutrophil granulocytes(90 days)
- Engraftment of thrombocytes(1 year)
- Other non-specified transplant complications(2 years)
研究者
Jonas Mattsson
Professor
Karolinska Institutet