Randomized Controlled Trial Comparing Single-dose and Divided-dose G-CSF for Peripheral Blood Stem Cell Mobilization in Healthy Donors for Allogeneic Hematopoietic Stem Cell Transplantation.
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 560
- 试验地点
- 8
- 主要终点
- Proportion of donors achieving a first apheresis yield of ≥ 4 × 10⁶ CD34⁺ cells/kg (donor weight).
研究概览
简要总结
National and international guidelines/consensus recommend G-CSF (granulocyte colony-stimulating factor) at 10 μg/kg/day as a single daily dose or divided into two daily doses for mobilization in healthy donors for allogeneic hematopoietic stem cell transplantation. However, there is no consensus or standard regarding single versus divided dosing, and high-quality evidence is lacking. Existing randomized controlled trials have small sample sizes and inconsistent conclusions, and none have focused on Asian population characteristics (e.g., body weight and drug metabolism differences). This study aims to provide level I evidence to optimize donor experience and define the optimal administration strategy.
Inclusion criteria: Healthy allogeneic stem cell donors aged 18-60 years, meeting institutional standard donor screening criteria (HLA matching, normal blood counts, normal liver and kidney function, negative infection screening), and providing written informed consent.
Primary endpoint: The rate of achieving a first apheresis yield of ≥ 4 × 10⁶ CD34⁺ cells/kg (donor body weight) after 5 days of G-CSF mobilization.
Secondary endpoints: The rate of achieving ≥ 2 × 10⁶ CD34⁺ cells/kg with at most one apheresis; time to myeloid, platelet, and erythroid engraftment in recipients; the proportion and composition of immune cells (CD34⁺, CD3⁺, CD19⁺, CD56⁺, etc.) in the apheresis product; donor adverse events; donor-reported outcomes; and the difference in CD34⁺ stem cell yields between single-dose and divided-dose mobilization.
Intervention: G-CSF will be administered at a total dose of 10 μg/kg/day, either as a single daily injection or divided into two equal daily injections.
This study is designed to investigate whether single-dose or divided-dose G-CSF administration is superior for mobilizing healthy donors in allogeneic hematopoietic stem cell transplantation.
详细描述
National and international guidelines/consensus recommend G-CSF (granulocyte colony-stimulating factor) at 10 μg/kg/day as a single daily dose or divided into two daily doses for mobilization in healthy donors for allogeneic hematopoietic stem cell transplantation. However, there is no consensus or standard regarding single versus divided dosing, and high-quality evidence is lacking. Existing randomized controlled trials have small sample sizes and inconsistent conclusions, and none have focused on Asian population characteristics (e.g., body weight and drug metabolism differences). This study aims to provide level I evidence to optimize donor experience and define the optimal administration strategy.
Inclusion criteria: Healthy allogeneic stem cell donors aged 18-60 years, meeting institutional standard donor screening criteria (HLA matching, normal blood counts, normal liver and kidney function, negative infection screening), and providing written informed consent.
Primary endpoint: The rate of achieving a first apheresis yield of ≥ 4 × 10⁶ CD34⁺ cells/kg (donor body weight) after 5 days of G-CSF mobilization.
Secondary endpoints: The rate of achieving ≥ 2 × 10⁶ CD34⁺ cells/kg with at most one apheresis; time to myeloid, platelet, and erythroid engraftment in recipients; the proportion and composition of immune cells (CD34⁺, CD3⁺, CD19⁺, CD56⁺, etc.) in the apheresis product; donor adverse events; donor-reported outcomes; and the difference in CD34⁺ stem cell yields between single-dose and divided-dose mobilization.
Intervention: G-CSF will be administered at a total dose of 10 μg/kg/day, either as a single daily injection or divided into two equal daily injections.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-65 years.
- •Provision of written informed consent.
- •White blood cell (WBC) count > 2.5 × 10⁹/L.
- •Absolute neutrophil count (ANC) > 1.5 × 10⁹/L and platelet count > 100 × 10⁹/L.
- •Deemed suitable as a donor by the investigator based on donor physical examination and HLA matching.
- •Body weight ≥ 40 kg for females and ≥ 45 kg for males.
排除标准
- •Currently having any disease or condition that, in the judgment of the investigator, would make the donor unsuitable for participation in this study, such as severe neurological, hepatic, renal, endocrine, cardiovascular, hematologic, gastrointestinal, respiratory, or metabolic diseases; malignancies; myeloproliferative disorders; or psychiatric illnesses.
- •Currently having an active infection requiring systemic therapy.
- •Allergy to the study drug.
- •Presence of a malignant tumor.
- •Untreated HBV infection with HBV-DNA above the lower limit of detection.
- •HIV infection.
- •Addition of any new medication within 2 weeks prior to entry into this study.
- •Female donors who are pregnant or breastfeeding.
研究组 & 干预措施
Divided-dose Arm
G-CSF 10 μg/kg per day divided into two equal subcutaneous doses daily for 5 days (up to 7 days if needed).
干预措施: Divided-dose Granulocyte colony-stimulating factor (G-CSF) (Drug)
Single-dose Arm
G-CSF 10 μg/kg administered subcutaneously once daily for 5 days (up to 7 days if needed based on CD34⁺ yield).
干预措施: Single-dose Granulocyte colony-stimulating factor (G-CSF) (Drug)
结局指标
主要结局
Proportion of donors achieving a first apheresis yield of ≥ 4 × 10⁶ CD34⁺ cells/kg (donor weight).
时间窗: From enrollment to the end of stem cell collection (8 weeks)
Proportion of donors achieving a first apheresis yield of ≥ 4 × 10⁶ CD34⁺ cells/kg (donor weight).
次要结局
- Proportion of donors achieving a yield of ≥ 2 × 10⁶ CD34⁺ cells/kg (donor weight) with no more than one apheresis.(From enrollment to the end of stem cell collection (8 weeks))
- Cumulative incidence rates of neutrophil engraftment in allogeneic stem cell transplant recipients.(28 days after transplantation)
- Cumulative incidence rates of platelet engraftment in allogeneic stem cell transplant recipients.(28 days after transplantation)
- Cumulative incidence rates of erythroid engraftment in allogeneic stem cell transplant recipients.(28 days after transplantation)
- The proportion and composition of immune cells (including CD34⁺, CD3⁺, CD19⁺, CD56⁺, etc.) in the apheresis product(From enrollment to the end of stem cell collection (8 weeks))
- Donor adverse events and recipient-reported outcomes(From enrollment to the end of stem cell collection (8 weeks))
- Comparison of peripheral blood CD34⁺ cell counts (cells/μL) on Days 1, 2, 3, 4, and 5 between healthy donors mobilized with single-dose versus divided-dose G-CSF(From enrollment to the end of stem cell collection (8 weeks))
- Comparison of the rate of engraftment failure in recipients between the two groups(From enrollment to the end of stem cell collection (8 weeks))
- Comparison of overall survival (OS) rates at 2 years in recipients between the two groups;(2 years post transplantation)
- Comparison of overall survival (OS) rates at 5 years in recipients between the two groups;(5 years post transplantation)
- Comparison of CD34⁺ stem cell yield in the apheresis product between the two groups(From enrollment to the end of stem cell collection (8 weeks))
研究者
Yi Luo
Professor
First Affiliated Hospital of Zhejiang University