Prospective Randomized Study on the Feasibility of Allogeneic Stem Cell Transplantation in Higher-risk-myelodysplastic Syndromes, Performed Upfront or Preceded by Azacitidine or Conventional Chemotherapy According to the BM-blast Proportion
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 274
- 试验地点
- 46
- 主要终点
- Feasibility of HSCT in terms of proportion of patients who receive HSCT of the total number of randomized patients
研究概览
简要总结
Open-label, randomized multicenter phase III non-inferiority study
详细描述
Open-label, randomized, prospective multicenter phase III study to compare the role of HMT followed by HSCT vs HSCT upfront in HR-MDS with <10% of BM blasts and of CHT vs HMT followed by HSCT in HR-MDS with >10% BM blasts in terms of feasibility of HSCT (non-inferiority trial).
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with newly diagnosed higher-risk MDS, including IPSS Intermediate-2 and high, and IPSS-R intermediate to very-high
- •Age 18-70 years
- •Previously untreated for HR-MDS
- •HSCT - eligible
- •Life expectancy ≥3 months;
- •Signed written informed consent according to ICH/EU/GCP and national local laws
- •Eastern Cooperative Oncology Group Performance Status Grade of 0-2
排除标准
- •Acute myeloid leukaemia with >20% blasts in BM or peripheral blood (PB);
- •concurrent malignancy diagnosed in the past 12 months (with the exception of skin basalioma);
- •severe renal, cardiac, liver or lung impairment;
- •pregnant or lactating or potentially fertile (both males and females), who have not agreed to avoid pregnancy during the trial period; Women of childbearing potential and men must agree to use effective contraception during and up to 3 months after treatment with azacitidine.
- •HIV infection; active, uncontrolled HCV or HBV infections or liver cirrhosis;
- •clinically relevant neurological or psychiatric diseases;
- •hypersensitivity (known or suspected) to AZA;
- •prior Treatments:
- •prior investigational drugs (within 30 days);
- •radiotherapy, chemotherapy, or cytotoxic therapy for non-MDS conditions within the previous 6 months;
- •growth factors (EPO, G-CSF or GM-CSF) during the previous 21 days;
- •androgenic hormones during the previous 14 days;
- •prior transplantation or cytotoxic therapy, including azacitidine, AZA or chemotherapy, administered to treat MDS (a previous treatment with Lenalidomide is admitted, provided that lenalidomide had been stopped at least 60 days before enrolment).
研究组 & 干预措施
Standard clinical treatment
If BM-blasts >= 10%: Conventional chemotherapy: induction one cycle (3+7 protocol) and one optional consolidation cycle, followed by HSCT if a suitable sibling or unrelated donor is available versus
If BM blasts are <10%: HSCT upfront
干预措施: Standard Chemotherapy (Drug)
Standard clinical treatment
If BM-blasts >= 10%: Conventional chemotherapy: induction one cycle (3+7 protocol) and one optional consolidation cycle, followed by HSCT if a suitable sibling or unrelated donor is available versus
If BM blasts are <10%: HSCT upfront
干预措施: Allogeneic stem cell transplantation (Procedure)
Experimental treatment
If BM-blasts >= 10%: Azacitidine (AZA) 75mg/sqm/day subcutaneously for 7 days every 28 days (1 cycle of 28 days) for at least 4 cycles, followed by HSCT if a suitable sibling or unrelated donor is available
If BM blasts are <10%: Azacitidine (AZA) 75mg/sqm/day subcutaneously for 7 days every 28 days (1 cycle of 28 days) for at least 4 cycles, followed by HSCT if a suitable sibling or unrelated donor is available
干预措施: Azacitidine (Drug)
Experimental treatment
If BM-blasts >= 10%: Azacitidine (AZA) 75mg/sqm/day subcutaneously for 7 days every 28 days (1 cycle of 28 days) for at least 4 cycles, followed by HSCT if a suitable sibling or unrelated donor is available
If BM blasts are <10%: Azacitidine (AZA) 75mg/sqm/day subcutaneously for 7 days every 28 days (1 cycle of 28 days) for at least 4 cycles, followed by HSCT if a suitable sibling or unrelated donor is available
干预措施: Allogeneic stem cell transplantation (Procedure)
结局指标
主要结局
Feasibility of HSCT in terms of proportion of patients who receive HSCT of the total number of randomized patients
时间窗: 4 years
Split patients in two categories: the feasibility of HSCT (ITT) in patients with HR-MDS with a proportion of bone marrow blasts below 10% and in patients with a proportion of BM blasts equal or greater than 10%.
次要结局
未报告次要终点