An Open, Multi-center, Randomized Trial Comparing Haploidentical HSCTs From Young Non-first-degree and Older First-degree Donors in Hematological Malignancies
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 232
- 试验地点
- 10
- 主要终点
- Cumulative incidence of transplant-related nonrelapse mortality (NRM)
研究概览
简要总结
An open, multi-center, randomized trial comparing haploidentical HSCTs from young non-first-degree and older first-degree donors in hematological malignancies
详细描述
This is an open, multi-center, randomized trial comparing the clinical outcomes of haploidentical HSCTs from young non-first-degree and older first-degree donors in hematological malignancies. This study is indicated for patients with hematological malignancies including acute leukemias and MDS who are eligible to haploidentical HSCTs. 2 groups of patients will be enrolled with 116 in each group. The clinical criteria including survival, relapse, transplantation-related mortality will be monitored.
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
- 13 Years 至 78 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient Inclusion Criteria:
- •Patient age 13-78 years
- •Absence of a suitable HLA identical related or unrelated hematopoietic stem cell donor
- •Absence of a suitable partially HLA-mismatched (haploidentical), first-degree related donor aged between 18 and 50
- •Presence of both HLA haploidentical young non-first-degree (age ≤ 40) and older first-degree (age >50) donors
- •Eligible diagnoses:
- •AML（excluding APL） with at least one of the following:
- •median- or high- risk according to the WHO prognostic stratification system
- •failure to achieve CR after 2 cycles of induction chemotherapy
- •AML arising from MDS or a myeloproliferative disorder, or secondary AML
- •patients in CR2 or beyond
- •Mixed-phenotype acute leukemia (MPAL) in morphological remission Acute lymphoblastic leukemia (T or B) in morphological remission
- •MDS with at least one of the following:
- •IPSS score of INT-2 or greater
- •IPSS score of INT-1 with life-threatening cytopenias, including those generally requiring greater than weekly transfusions
- •A first allo-HCT
- •Adequate end-organ function
- •ECOG performance status < 2
- •No other contraindications for HSCT
- •Signature of the informed consent
排除标准
- •Availability of suitable HLA identical related or unrelated hematopoietic stem cell donors
- •Availability of suitable partially HLA-mismatched (haploidentical), first-degree related donor aged between 18 and 50
- •Not the first allo-HCT
- •Presence of uncontrolled bacterial, viral, or fungal infection
- •Patients with severe heart, lung, liver and kidney insufficiency
- •HIV-positive patients
- •Women of childbearing potential who are pregnant (β-HCG+) or breast feeding
- •Patients with a psychiatric history
- •ECOG performance status ≥ 2
- •Patients with malignancies other than the primary disease
- •Refusal to sign the informed consent
- •Donor Inclusion Criteria:
- •The donor and recipient must be HLA haploidentical
- •Meets institutional selection criteria and medically fit to donate
- •Lack of recipient anti-donor HLA antibody
- •Donor Exclusion Criteria:
- •The donor and recipient are HLA identical
- •Has not donated blood products to recipient
研究组 & 干预措施
Non-first-degree donor
Each patient receive graft from a non-first degree donor aged ≤40
Conditoning regimens are decided by each center accoding to disease risk, patient age & status, and cormobidity index.The centers are required to use the same principle when treating NFD and FD patients. The used protocol in the current study included:
For MAC: use BU-CY-based (described in detail)
For RIC: use BUFlu:
Drug: Fludarabine 30 mg/m²/kg, administered IV d-10 through d-5. Drug: Busulfan, 3.2 mg/kg/day administered IV day -6 (BU2) or -7 through -5 (BU3).
Other conditioning regimen may include:
TBF, FluMel, FBM, Cy-TBI, Flu-TBI.
干预措施: Allogeneic HSCT (Procedure)
First-degree donor
Each patients receive graft from a first-degree donor aged >50
Conditoning regimens are decided by each center accoding to disease risk, patient age & status, and cormobidity index.The centers are required to use the same principle when treating NFD and FD patients. The used protocol in the current study included: For MAC: use BU-CY-based (described in detail) For RIC: use BUFlu: Drug: Fludarabine 30 mg/m²/kg, administered IV d-10 through d-5. Drug: Busulfan, 3.2 mg/kg/day administered IV day -6 (BU2) or -7 through -5 (BU3). Other conditioning regimen may include: TBF, FluMel, FBM, Cy-TBI, Flu-TBI.
干预措施: Me-CCNU (Drug)
First-degree donor
Each patients receive graft from a first-degree donor aged >50
Conditoning regimens are decided by each center accoding to disease risk, patient age & status, and cormobidity index.The centers are required to use the same principle when treating NFD and FD patients. The used protocol in the current study included: For MAC: use BU-CY-based (described in detail) For RIC: use BUFlu: Drug: Fludarabine 30 mg/m²/kg, administered IV d-10 through d-5. Drug: Busulfan, 3.2 mg/kg/day administered IV day -6 (BU2) or -7 through -5 (BU3). Other conditioning regimen may include: TBF, FluMel, FBM, Cy-TBI, Flu-TBI.
干预措施: Cyclophosphamide (Drug)
First-degree donor
Each patients receive graft from a first-degree donor aged >50
Conditoning regimens are decided by each center accoding to disease risk, patient age & status, and cormobidity index.The centers are required to use the same principle when treating NFD and FD patients. The used protocol in the current study included: For MAC: use BU-CY-based (described in detail) For RIC: use BUFlu: Drug: Fludarabine 30 mg/m²/kg, administered IV d-10 through d-5. Drug: Busulfan, 3.2 mg/kg/day administered IV day -6 (BU2) or -7 through -5 (BU3). Other conditioning regimen may include: TBF, FluMel, FBM, Cy-TBI, Flu-TBI.
干预措施: Allogeneic HSCT (Procedure)
First-degree donor
Each patients receive graft from a first-degree donor aged >50
Conditoning regimens are decided by each center accoding to disease risk, patient age & status, and cormobidity index.The centers are required to use the same principle when treating NFD and FD patients. The used protocol in the current study included: For MAC: use BU-CY-based (described in detail) For RIC: use BUFlu: Drug: Fludarabine 30 mg/m²/kg, administered IV d-10 through d-5. Drug: Busulfan, 3.2 mg/kg/day administered IV day -6 (BU2) or -7 through -5 (BU3). Other conditioning regimen may include: TBF, FluMel, FBM, Cy-TBI, Flu-TBI.
干预措施: Mycophenolate Mofetil (Drug)
Non-first-degree donor
Each patient receive graft from a non-first degree donor aged ≤40
Conditoning regimens are decided by each center accoding to disease risk, patient age & status, and cormobidity index.The centers are required to use the same principle when treating NFD and FD patients. The used protocol in the current study included:
For MAC: use BU-CY-based (described in detail)
For RIC: use BUFlu:
Drug: Fludarabine 30 mg/m²/kg, administered IV d-10 through d-5. Drug: Busulfan, 3.2 mg/kg/day administered IV day -6 (BU2) or -7 through -5 (BU3).
Other conditioning regimen may include:
TBF, FluMel, FBM, Cy-TBI, Flu-TBI.
干预措施: Cyclophosphamide (Drug)
Non-first-degree donor
Each patient receive graft from a non-first degree donor aged ≤40
Conditoning regimens are decided by each center accoding to disease risk, patient age & status, and cormobidity index.The centers are required to use the same principle when treating NFD and FD patients. The used protocol in the current study included:
For MAC: use BU-CY-based (described in detail)
For RIC: use BUFlu:
Drug: Fludarabine 30 mg/m²/kg, administered IV d-10 through d-5. Drug: Busulfan, 3.2 mg/kg/day administered IV day -6 (BU2) or -7 through -5 (BU3).
Other conditioning regimen may include:
TBF, FluMel, FBM, Cy-TBI, Flu-TBI.
干预措施: Rabbit antithymocyte globulin (Drug)
Non-first-degree donor
Each patient receive graft from a non-first degree donor aged ≤40
Conditoning regimens are decided by each center accoding to disease risk, patient age & status, and cormobidity index.The centers are required to use the same principle when treating NFD and FD patients. The used protocol in the current study included:
For MAC: use BU-CY-based (described in detail)
For RIC: use BUFlu:
Drug: Fludarabine 30 mg/m²/kg, administered IV d-10 through d-5. Drug: Busulfan, 3.2 mg/kg/day administered IV day -6 (BU2) or -7 through -5 (BU3).
Other conditioning regimen may include:
TBF, FluMel, FBM, Cy-TBI, Flu-TBI.
干预措施: Mycophenolate Mofetil (Drug)
Non-first-degree donor
Each patient receive graft from a non-first degree donor aged ≤40
Conditoning regimens are decided by each center accoding to disease risk, patient age & status, and cormobidity index.The centers are required to use the same principle when treating NFD and FD patients. The used protocol in the current study included:
For MAC: use BU-CY-based (described in detail)
For RIC: use BUFlu:
Drug: Fludarabine 30 mg/m²/kg, administered IV d-10 through d-5. Drug: Busulfan, 3.2 mg/kg/day administered IV day -6 (BU2) or -7 through -5 (BU3).
Other conditioning regimen may include:
TBF, FluMel, FBM, Cy-TBI, Flu-TBI.
干预措施: Busulfan (Drug)
Non-first-degree donor
Each patient receive graft from a non-first degree donor aged ≤40
Conditoning regimens are decided by each center accoding to disease risk, patient age & status, and cormobidity index.The centers are required to use the same principle when treating NFD and FD patients. The used protocol in the current study included:
For MAC: use BU-CY-based (described in detail)
For RIC: use BUFlu:
Drug: Fludarabine 30 mg/m²/kg, administered IV d-10 through d-5. Drug: Busulfan, 3.2 mg/kg/day administered IV day -6 (BU2) or -7 through -5 (BU3).
Other conditioning regimen may include:
TBF, FluMel, FBM, Cy-TBI, Flu-TBI.
干预措施: Cytarabine (Drug)
Non-first-degree donor
Each patient receive graft from a non-first degree donor aged ≤40
Conditoning regimens are decided by each center accoding to disease risk, patient age & status, and cormobidity index.The centers are required to use the same principle when treating NFD and FD patients. The used protocol in the current study included:
For MAC: use BU-CY-based (described in detail)
For RIC: use BUFlu:
Drug: Fludarabine 30 mg/m²/kg, administered IV d-10 through d-5. Drug: Busulfan, 3.2 mg/kg/day administered IV day -6 (BU2) or -7 through -5 (BU3).
Other conditioning regimen may include:
TBF, FluMel, FBM, Cy-TBI, Flu-TBI.
干预措施: Me-CCNU (Drug)
First-degree donor
Each patients receive graft from a first-degree donor aged >50
Conditoning regimens are decided by each center accoding to disease risk, patient age & status, and cormobidity index.The centers are required to use the same principle when treating NFD and FD patients. The used protocol in the current study included: For MAC: use BU-CY-based (described in detail) For RIC: use BUFlu: Drug: Fludarabine 30 mg/m²/kg, administered IV d-10 through d-5. Drug: Busulfan, 3.2 mg/kg/day administered IV day -6 (BU2) or -7 through -5 (BU3). Other conditioning regimen may include: TBF, FluMel, FBM, Cy-TBI, Flu-TBI.
干预措施: Cytarabine (Drug)
Non-first-degree donor
Each patient receive graft from a non-first degree donor aged ≤40
Conditoning regimens are decided by each center accoding to disease risk, patient age & status, and cormobidity index.The centers are required to use the same principle when treating NFD and FD patients. The used protocol in the current study included:
For MAC: use BU-CY-based (described in detail)
For RIC: use BUFlu:
Drug: Fludarabine 30 mg/m²/kg, administered IV d-10 through d-5. Drug: Busulfan, 3.2 mg/kg/day administered IV day -6 (BU2) or -7 through -5 (BU3).
Other conditioning regimen may include:
TBF, FluMel, FBM, Cy-TBI, Flu-TBI.
干预措施: Cyclosporin A (Drug)
Non-first-degree donor
Each patient receive graft from a non-first degree donor aged ≤40
Conditoning regimens are decided by each center accoding to disease risk, patient age & status, and cormobidity index.The centers are required to use the same principle when treating NFD and FD patients. The used protocol in the current study included:
For MAC: use BU-CY-based (described in detail)
For RIC: use BUFlu:
Drug: Fludarabine 30 mg/m²/kg, administered IV d-10 through d-5. Drug: Busulfan, 3.2 mg/kg/day administered IV day -6 (BU2) or -7 through -5 (BU3).
Other conditioning regimen may include:
TBF, FluMel, FBM, Cy-TBI, Flu-TBI.
干预措施: MTX (Drug)
First-degree donor
Each patients receive graft from a first-degree donor aged >50
Conditoning regimens are decided by each center accoding to disease risk, patient age & status, and cormobidity index.The centers are required to use the same principle when treating NFD and FD patients. The used protocol in the current study included: For MAC: use BU-CY-based (described in detail) For RIC: use BUFlu: Drug: Fludarabine 30 mg/m²/kg, administered IV d-10 through d-5. Drug: Busulfan, 3.2 mg/kg/day administered IV day -6 (BU2) or -7 through -5 (BU3). Other conditioning regimen may include: TBF, FluMel, FBM, Cy-TBI, Flu-TBI.
干预措施: Rabbit antithymocyte globulin (Drug)
First-degree donor
Each patients receive graft from a first-degree donor aged >50
Conditoning regimens are decided by each center accoding to disease risk, patient age & status, and cormobidity index.The centers are required to use the same principle when treating NFD and FD patients. The used protocol in the current study included: For MAC: use BU-CY-based (described in detail) For RIC: use BUFlu: Drug: Fludarabine 30 mg/m²/kg, administered IV d-10 through d-5. Drug: Busulfan, 3.2 mg/kg/day administered IV day -6 (BU2) or -7 through -5 (BU3). Other conditioning regimen may include: TBF, FluMel, FBM, Cy-TBI, Flu-TBI.
干预措施: Busulfan (Drug)
First-degree donor
Each patients receive graft from a first-degree donor aged >50
Conditoning regimens are decided by each center accoding to disease risk, patient age & status, and cormobidity index.The centers are required to use the same principle when treating NFD and FD patients. The used protocol in the current study included: For MAC: use BU-CY-based (described in detail) For RIC: use BUFlu: Drug: Fludarabine 30 mg/m²/kg, administered IV d-10 through d-5. Drug: Busulfan, 3.2 mg/kg/day administered IV day -6 (BU2) or -7 through -5 (BU3). Other conditioning regimen may include: TBF, FluMel, FBM, Cy-TBI, Flu-TBI.
干预措施: MTX (Drug)
First-degree donor
Each patients receive graft from a first-degree donor aged >50
Conditoning regimens are decided by each center accoding to disease risk, patient age & status, and cormobidity index.The centers are required to use the same principle when treating NFD and FD patients. The used protocol in the current study included: For MAC: use BU-CY-based (described in detail) For RIC: use BUFlu: Drug: Fludarabine 30 mg/m²/kg, administered IV d-10 through d-5. Drug: Busulfan, 3.2 mg/kg/day administered IV day -6 (BU2) or -7 through -5 (BU3). Other conditioning regimen may include: TBF, FluMel, FBM, Cy-TBI, Flu-TBI.
干预措施: Cyclosporin A (Drug)
结局指标
主要结局
Cumulative incidence of transplant-related nonrelapse mortality (NRM)
时间窗: 2 years
All patients will be tracked from Day 0 to date of first objective disease progression, death from any cause, or last patient evaluation. Patients who have not progressed or died will be censored at the last date they were assessed and deemed free of relapse or progression.
Overall survival (OS)
时间窗: 2 years
All patients will be tracked from Day 0 to date of first objective disease progression, death from any cause, or last patient evaluation. Patients who have not progressed or died will be censored at the last date they were assessed and deemed free of relapse or progression.
次要结局
- Cumulative incidence of transplant-related nonrelapse mortality (NRM)(2 years)
- Cumulative incidence of total acute and grade II-IV acute GVHD(180 days)
- Cumulative incidence of total and and moderate-severe chronic GVHD(2 years)
- Overall survival (OS)(2 years)
- Progression-free survival (PFS)(2 years)
- Cumulative incidence of disease relapse or progression(2 years)
- GVHD-free, relapse-free survival (GRFS)(2 years)
- Cumulative incidence of chronic GVHD(2 years)
- Cumulative incidence of acute grade II-IV GVHD(180 days)
研究者
Yi Luo
Clinical Professor
First Affiliated Hospital of Zhejiang University