A Single-Arm, Prospective Clinical Study of the Efficacy and Safety of VABu Conditioning Regimen in Allogeneic Hematopoietic Stem Cell Transplantation for Non-High-Risk AML Patients in CR1 With Low Performance Status (ECOG ≥ 2) or High Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI ≥ 2)
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 42
- 试验地点
- 1
- 主要终点
- 2-Year Overall Survival (OS)
研究概览
简要总结
This study evaluates the effectiveness and safety of a new conditioning regimen called VABu before stem cell transplantation in patients with acute myeloid leukemia (AML) who are in their first complete remission (CR1), classified as non-high-risk per ELN 2022 guidelines, but have poor physical condition (ECOG performance status ≥ 2) or high comorbidity burden (HCT-CI ≥ 2). VABu combines venetoclax, azacitidine (or decitabine as an alternative), and busulfan. This is a single-arm, prospective study with 42 participants. All participants will receive the VABu regimen followed by stem cell transplantation. The primary outcome measure is 2-year overall survival (OS). Secondary outcomes include 2-year relapse-free survival (RFS), transplant-related mortality (TRM), engraftment failure rate, bloodstream infection (BSI), and 2-year all-cause mortality and non-relapse mortality (NRM). The study is conducted at the First Affiliated Hospital of Soochow University.
详细描述
Acute myeloid leukemia (AML) is the most common acute leukemia in adults. For patients who are unfit for intensive chemotherapy due to poor performance status or high comorbidity burden, allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only potential curative treatment. However, these patients often have low transplantation rates and suboptimal outcomes with reduced-intensity conditioning regimens. Venetoclax combined with azacitidine has been established as the standard of care for unfit AML patients, demonstrating high remission rates and good tolerability. Building on this, our center has previously explored the VABu regimen (venetoclax, azacitidine, and busulfan) as a conditioning therapy in elderly AML patients undergoing allo-HSCT, with preliminary results showing reduced chemotherapy-related toxicity and a 2-year overall survival rate of approximately 70%.
This is a single-arm, prospective, single-center study. A total of 42 participants will be enrolled. Eligible participants are patients aged 18 to 70 years with non-APL AML who have achieved first complete remission (CR1), are classified as non-high-risk per ELN 2022 guidelines, and have either ECOG performance status ≥ 2 (not due to leukemia) or HCT-CI ≥ 2. All participants will receive the VABu conditioning regimen followed by allo-HSCT. The VABu regimen consists of venetoclax 600 mg/m² once daily on days -12 to -7, azacitidine 75 mg/m² once daily on days -11 to -7 (or decitabine 20 mg/m² for 5 days), cytarabine 2.0 g/m² every 12 hours on day -6, busulfan 0.8 mg/kg every 6 hours on days -5 to -3, and antithymocyte globulin (ATG) at 2.5 mg/kg/day according to donor type (haploidentical/unrelated donors on days -5 to -2, or matched sibling donors on days -3 to -2). Hematopoietic stem cell infusion occurs on day 0, followed by standard graft-versus-host disease (GVHD) prophylaxis.
The primary outcome measure is 2-year overall survival (OS). Secondary outcome measures include 2-year relapse-free survival (RFS), transplant-related mortality (TRM), engraftment failure rate, bloodstream infection (BSI), and 2-year all-cause mortality and non-relapse mortality (NRM). Safety will be monitored through adverse event collection and grading per CTCAE 5.0 criteria. Follow-up assessments are scheduled at weeks 1, 2, 3, 4, and months 2, 3, 6, 12 post-transplantation. The study period is from August 2026 to July 2029. Statistical analyses will be performed using SPSS and R, with Kaplan-Meier method for OS, and Cox regression and logistic regression for multivariate analyses.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 to 70 years.
- •Diagnosis of acute myeloid leukemia (AML) other than acute promyelocytic leukemia (APL), with first complete remission (CR1) achieved after induction chemotherapy.
- •Classified as non-high-risk per ELN 2022 risk stratification guidelines.
- •ECOG performance status ≥ 2 (not due to leukemia) OR Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) ≥
- •Willing to undergo allogeneic hematopoietic stem cell transplantation and has a suitable donor.
- •Voluntarily signs informed consent form after full understanding of the study.
排除标准
- •Allergy to any component of the study drugs.
- •Psychiatric or psychological disorders that prevent cooperation with treatment.
- •Uncontrolled systemic or local severe infection.
- •Severe dysfunction of major organs (heart, lung, liver, kidney) that, in the investigator's opinion, makes the patient unsuitable for enrollment.
- •Currently participating in or planning to participate in any other clinical study.
- •Any other conditions that, in the investigator's opinion, make the patient unsuitable for enrollment.
研究组 & 干预措施
VABu Conditioning Regimen
Participants receive the VABu conditioning regimen followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT). The VABu regimen consists of venetoclax 600 mg/m² once daily on days -12 to -7, azacitidine 75 mg/m² once daily on days -11 to -7 (or decitabine 20 mg/m² for 5 days), cytarabine 2.0 g/m² every 12 hours on day -6, and busulfan 0.8 mg/kg every 6 hours on days -5 to -3. Antithymocyte globulin (ATG) is administered at 2.5 mg/kg/day according to donor type: haploidentical or unrelated donors receive ATG on days -5 to -2 (4 doses), while matched sibling donors receive ATG on days -3 to -2 (2 doses). Hematopoietic stem cell infusion occurs on day 0, followed by standard graft-versus-host disease (GVHD) prophylaxis.
干预措施: Decitabine 20 mg/m²/day for 5 days (Drug)
VABu Conditioning Regimen
Participants receive the VABu conditioning regimen followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT). The VABu regimen consists of venetoclax 600 mg/m² once daily on days -12 to -7, azacitidine 75 mg/m² once daily on days -11 to -7 (or decitabine 20 mg/m² for 5 days), cytarabine 2.0 g/m² every 12 hours on day -6, and busulfan 0.8 mg/kg every 6 hours on days -5 to -3. Antithymocyte globulin (ATG) is administered at 2.5 mg/kg/day according to donor type: haploidentical or unrelated donors receive ATG on days -5 to -2 (4 doses), while matched sibling donors receive ATG on days -3 to -2 (2 doses). Hematopoietic stem cell infusion occurs on day 0, followed by standard graft-versus-host disease (GVHD) prophylaxis.
干预措施: Antithymocyte Globulin (ATG) (Drug)
VABu Conditioning Regimen
Participants receive the VABu conditioning regimen followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT). The VABu regimen consists of venetoclax 600 mg/m² once daily on days -12 to -7, azacitidine 75 mg/m² once daily on days -11 to -7 (or decitabine 20 mg/m² for 5 days), cytarabine 2.0 g/m² every 12 hours on day -6, and busulfan 0.8 mg/kg every 6 hours on days -5 to -3. Antithymocyte globulin (ATG) is administered at 2.5 mg/kg/day according to donor type: haploidentical or unrelated donors receive ATG on days -5 to -2 (4 doses), while matched sibling donors receive ATG on days -3 to -2 (2 doses). Hematopoietic stem cell infusion occurs on day 0, followed by standard graft-versus-host disease (GVHD) prophylaxis.
干预措施: Venetoclax (Drug)
VABu Conditioning Regimen
Participants receive the VABu conditioning regimen followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT). The VABu regimen consists of venetoclax 600 mg/m² once daily on days -12 to -7, azacitidine 75 mg/m² once daily on days -11 to -7 (or decitabine 20 mg/m² for 5 days), cytarabine 2.0 g/m² every 12 hours on day -6, and busulfan 0.8 mg/kg every 6 hours on days -5 to -3. Antithymocyte globulin (ATG) is administered at 2.5 mg/kg/day according to donor type: haploidentical or unrelated donors receive ATG on days -5 to -2 (4 doses), while matched sibling donors receive ATG on days -3 to -2 (2 doses). Hematopoietic stem cell infusion occurs on day 0, followed by standard graft-versus-host disease (GVHD) prophylaxis.
干预措施: Busulfan (BU) (Drug)
VABu Conditioning Regimen
Participants receive the VABu conditioning regimen followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT). The VABu regimen consists of venetoclax 600 mg/m² once daily on days -12 to -7, azacitidine 75 mg/m² once daily on days -11 to -7 (or decitabine 20 mg/m² for 5 days), cytarabine 2.0 g/m² every 12 hours on day -6, and busulfan 0.8 mg/kg every 6 hours on days -5 to -3. Antithymocyte globulin (ATG) is administered at 2.5 mg/kg/day according to donor type: haploidentical or unrelated donors receive ATG on days -5 to -2 (4 doses), while matched sibling donors receive ATG on days -3 to -2 (2 doses). Hematopoietic stem cell infusion occurs on day 0, followed by standard graft-versus-host disease (GVHD) prophylaxis.
干预措施: Cytarabine (Ara-C) (Drug)
VABu Conditioning Regimen
Participants receive the VABu conditioning regimen followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT). The VABu regimen consists of venetoclax 600 mg/m² once daily on days -12 to -7, azacitidine 75 mg/m² once daily on days -11 to -7 (or decitabine 20 mg/m² for 5 days), cytarabine 2.0 g/m² every 12 hours on day -6, and busulfan 0.8 mg/kg every 6 hours on days -5 to -3. Antithymocyte globulin (ATG) is administered at 2.5 mg/kg/day according to donor type: haploidentical or unrelated donors receive ATG on days -5 to -2 (4 doses), while matched sibling donors receive ATG on days -3 to -2 (2 doses). Hematopoietic stem cell infusion occurs on day 0, followed by standard graft-versus-host disease (GVHD) prophylaxis.
干预措施: Azacitidine (AZA) (Drug)
结局指标
主要结局
2-Year Overall Survival (OS)
时间窗: 2 years
Overall survival is defined as the time from enrollment to death from any cause. Participants alive at the end of follow-up will be censored at their last known alive date.
次要结局
- 2-Year Relapse-Free Survival (RFS)(2 years)
- 2-Year All-Cause Mortality, Transplant-Related Mortality (TRM), and Non-Relapse Mortality (NRM)(2 years)
- Engraftment Failure Rate(Day 28 post-transplantation)
- Bloodstream Infection (BSI) Rate(Day 28 post-transplantation)