Interferon-α Prevents Leukemia Relapse of AML Patients Undergoing HLA-identical Allogeneic Hematopoietic Stem Cell Transplantation With Pretransplant MRD
试验速览
- 阶段
- 不适用
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- cumulative incidence of relapse
研究概览
简要总结
Allogeneic stem cell transplantation (SCT) remains a powerful therapeutic modality for patients with acute myeloid leukemia (AML).The superior clinical outcomes of allogeneic human SCT versus chemotherapy alone as post-remission treatment could be related to the graft-versus-leukemia (GVL) effects of recovered donor T cells. Our previous study investigated both the association of MRD status with transplant outcomes in haplo-SCT and matched sibling donor transplantation(MSDT)， and also possible differences in the transplant outcomes of patients with positive pre-MRD (as determined by MFC) who underwent haplo-SCT versus MSDT. It provided new evidence that unmanipulated haplo-SCT is superior to matched sibling donor transplantation in eradicating pre-transplantation MRD, indicating that unmanipulated haploidentical allografts have stronger GVL effects.As to the AML patients in standard-risk, who have a positive MRD before MSDT, whether these patients should be given any relapse prevention is the question to be answered in this study. Interferon α-2b exerts a relatively strong immunomodulatory effect. It can kill AL cells by regulating T-cell and/or natural killer cell functions.Consequently, interferon α-2b may have potential value for high-risk AL patients after transplantation. The study hypothesis: Using interferon α-2b following hematopoietic stem cell transplantation in patients with standard-risk AML can further reduce relapse rate and improve leukemia-free survival.
详细描述
The standard-risk AML patients (18-60 years) receiving HLA-identical allogeneic stem cell transplantation in Peking University Institute of Hematology will be enrolled in this study if their MRD were positive before SCT, in CR1/CR2, remain in CR and MRD negative in the first two months after transplantation. The patients in this study will be treated with interferon-alpha injection twice a week (3 million units / time, iH) since the third month posttransplant. If the patients were well tolerated, the interferon-alpha treatment will continue 6 months. All the enrolled patients will undergo MRD monitoring after SCT as the same as the routine procedure. Bone marrow examination will be performed at the regular time points (+1, 2,3, 4, 5, 6, 9, 12 month) and 8-colour flow cytometry and RQ-PCR-based WT1 examination will be empolyed to evaluate MRD and disease status. Based on the statistical calculation, in order to reduce the incidence of relapse from 40% (previous data) to 15% (the cumulative incidence of relapse in pre-MRD- AML patients), total 29 patients will be enrolled. The main side effects might related to interferon-alpha include induction of severe GVHD, hematological toxicity and Flu - like symptoms. If the patients met the following criteria, they will withdraw from the trial: 1）met the combined criteria for positive MRD (MRDco+) which was defined as 2 consecutive FCM+ or WT1+ results or both FCM+ and WT1+ in a single sample within 1 year after transplantation; 2）hematological relapse; 3) grade III or IV acute GVHD, or moderate/ severe chronic GVHD; 4) severe infection; 5) grade IV hematological toxicity; 6) organ failure; 7) death; 8) patients refuse to continue the interferon-alpha treatment. The main end point of the study is one-year cumulative incidence of relapse. the second end points include OS, NRM, DFS, MRD, GVHD, infection and hematological toxicity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 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
- •standard-risk AML in CR1/CR2
- •without t(9;22) and t(15;17)
- •receive HLA-identical transplantation
- •with positive MRD before transplantation (measured by flow cytometry)
- •CR within the first two months posttransplantation and MRD is negative
- •between 18-60 years
排除标准
- •uncontrolled GVHD
- •be in myelosuppression (WBC<1.5x10^9/L, ANC<0.5×10^9/L，PLT<25×10^9/L,HB<65g/L)
- •severe infection
- •organ failure
- •the patients do not agree to participate in the study
研究组 & 干预措施
Interferon alpha group
The patients in arm will be receive interferon alpha injection (3 million U/time)twice a week, as the intervention since the third month after HLA-identical transplantation.
干预措施: Interferon-alpha (Drug)
结局指标
主要结局
cumulative incidence of relapse
时间窗: within the first year after transplantation
the cumulative incidence of relapse
次要结局
- acute GVHD(within 100 days after transplantation)
- OS(within the first year after transplantation)
- DFS(within the first year after transplantation)
- NRM(within the first year after transplantation)
- MRD(within the first year after transplantation)
- chronic GVHD(within the first year after transplantation)
- infection(within the first year after transplantation)
研究者
Xiaojun Huang,MD
Director of Peking University Institute of Hematology
Peking University People's Hospital