Granulocyte Colony-Stimulating Factor (G-CSF) Mobilization
Conditions
Keywords
CD34, G-CSF, Allo-HSCT
Brief summary
Healthy donors are commonly mobilized with granulocyte colony-stimulating factor (G-CSF) to collect peripheral blood stem cells for allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the efficiency of mobilization varies among donors, and suboptimal mobilization may require additional collection procedures or rescue strategies. This prospective, multicenter, randomized trial evaluates whether the timing of daily G-CSF administration (morning vs evening) affects the level of circulating CD34+ cells in healthy donors. Participants will be randomly assigned to receive subcutaneous G-CSF once daily for 4-5 consecutive days either at 08:00 (±15 minutes) or at 20:00 (±15 minutes). The goal of the study is to identify a practical dosing schedule that may improve stem cell mobilization and streamline donor collection procedures. The study protocol was substantially amended following approval by the Institutional Review Board. The amendments included revisions to the G-CSF administration regimen, the primary and secondary outcome measures, and the assessment schedule. Enrollment under the revised protocol commenced on 1st Nov. Participants enrolled under the previous protocol version will be documented separately and will not be included in the prespecified primary analysis of the revised-protocol cohort.
Detailed description
Background and Rationale Peripheral blood stem cell collection after G-CSF mobilization is the most widely used donation approach for allo-HSCT. Donor mobilization outcomes exhibit inter-individual variability, and donors with lower circulating CD34+ levels may require longer processing volumes, additional collection days, or rescue mobilization. Circadian biology may influence hematopoietic cell trafficking and cytokine responses, suggesting that the administration timing of G-CSF could affect mobilization intensity and collection efficiency. This trial tests whether a simple, operational change in dosing time can improve pre-apheresis CD34+ levels in healthy donors. Study Design This is a prospective, multicenter, stratified randomized controlled trial with two parallel arms. The study is open-label due to the nature of the intervention (fixed dosing times), while the statistician will remain blinded to group allocation until database lock. Allocation is stratified by donor age (\<40 vs ≥40 years) and sex to balance key donor characteristics across arms. Interventions and Procedures Eligible healthy donors will receive subcutaneous G-CSF at 10 μg/kg once daily for 4-5 consecutive days (Day 1 to Day 5, according to the first day collection efficacy), assigned to one of the following schedules: Morning group: 08:00 (±15 minutes) each day Evening group: 20:00 (±15 minutes) each day The first apheresis session is scheduled to begin after the forth G-CSF dose. Collection targets are based on recipient weight, with standard operational procedures for conducting a second collection day if the first-day yield does not meet the target. If peripheral blood CD34+ is low after the final G-CSF dose, centers may apply rescue mobilization per local practice, and such use will be recorded for sensitivity analyses. Outcome Measures Primary Outcome: To compare peripheral blood CD34+ cell counts (cells/μL) between healthy donors receiving morning (08:00) versus evening (20:00) G-CSF administration, measured at a standardized clock time of 11:30 (±15 minutes), after the fourth G-CSF dose and immediately before the first apheresis session. Sample Size and Analysis Overview A total of 160 donors (80 per group) will be enrolled to provide adequate power for detecting clinically meaningful differences in the primary endpoint while allowing for non-evaluable cases. The primary analysis will follow the intention-to-treat principle, with additional per-protocol and sensitivity analyses as appropriate, including analyses accounting for rescue mobilization when applicable. Safety Monitoring and Follow-up Donors will be monitored with clinical assessment and routine laboratory testing during the mobilization period and on collection days. Adverse events commonly associated with G-CSF (e.g., bone pain) and donation-related events will be recorded and managed per standard-of-care practices. Donors will be followed through approximately Day 30 to capture delayed or persistent adverse events.
Interventions
Subcutaneous recombinant human G-CSF (7.5 μg/kg once daily) administered for 4 consecutive days. Participants are assigned to a fixed dosing time: 08:00 (±15 minutes) or 20:00 (±15 minutes).
Sponsors
First Affiliated Hospital of Zhejiang University
The First Affiliated Hospital of Zhengzhou University
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Tongji Hospital
Ruijin Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Intervention model description
This is a multicenter, stratified, randomized parallel-group trial. Healthy donors are assigned 1:1 to morning vs evening once-daily G-CSF dosing (08:00±15 min vs 20:00±15 min) for 4 consecutive days. Randomization uses block randomization and is stratified by donor age (\<40 vs ≥40 years) and sex.
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Age 18-55 years 2. HLA matching appropriate for intended allo-HSCT recipient and meets donor medical evaluation criteria 3. Body weight ≥35 kg and adequate blood volume/BSA for apheresis 4. Karnofsky score ≥80 5. Screening labs meet thresholds (Hb/platelets/ANC, liver/renal/coagulation), no splenomegaly, pregnancy test negative if applicable 6. Written informed consent 7. Stable circadian rhythm before mobilization (no night shift/no ≥3 time-zone travel; avoid melatonin/sedatives or other agents affecting sleep/circadian rhythm)
Exclusion criteria
1. Prior/current hematologic or immune diseases (e.g., aplastic anemia, leukemia, lymphoma, autoimmune disease) 2. Significant cardiovascular/structural heart disease, uncontrolled hypertension, uncontrolled diabetes 3. Neurologic/psychiatric disorders affecting adherence 4. Sleep/circadian disorders; recent night shift or ≥3 time-zone travel 5. Prohibited medications (e.g., beta-blockers, systemic steroids \>10 mg prednisone-equivalent ≥7 days, melatonin/psychotropics; recent G-CSF/GM-CSF/CXCR4 inhibitor use) 6. Severe allergy to G-CSF or components
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Peripheral Blood CD34+ Cell Count before the first apheresis session | After the fourth G-CSF dose, immediately before the first apheresis session (11:30 ±15 minutes). | Peripheral blood CD34+ cell count (cells/μL) measured at a fixed clock time of 11:30 (±15 minutes), after the fourth G-CSF dose and immediately before the first apheresis session, scheduled to begin at 12:00 in both treatment groups. CD34+ cell counts will be determined using standardized flow cytometry procedures. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CD34+ Cell Yield During the First Apheresis Session | At completion of the first apheresis session following the fourth G-CSF dose. | Total number of CD34+ cells collected during the first apheresis session, normalized to donor body weight and expressed as ×10⁶ CD34+ cells/kg. |
| Peripheral Blood CD34+ Cell Count before the second apheresis session | After the fifth G-CSF dose, immediately before the second apheresis session (11:30 ±15 minutes). | Peripheral blood CD34+ cell count (cells/μL) measured at a fixed clock time of 11:30 (±15 minutes), after the fifth G-CSF dose and immediately before the second apheresis session, scheduled to begin at 12:00 in both treatment groups. CD34+ cell counts will be determined using standardized flow cytometry procedures. |
| Peripheral Blood CD34+ Cell Count 12 Hours After the Fourth G-CSF Dose | 12 (±1) hours after the fourth G-CSF dose, regardless of the timing of the first apheresis session. | Peripheral blood CD34+ cell count (cells/μL) measured 12 (±1) hours after the fourth G-CSF dose using standardized flow cytometry procedures. |
| G-CSF Dose Escalation | From the first apheresis session until completion of the final apheresis session, typically within 2 consecutive days and up to 3 consecutive days. | Proportion of donors requiring an increase in the daily G-CSF dose above the protocol-specified 10 μg/kg/day because of inadequate mobilization or insufficient CD34+ cell yield. Routine administration of an additional fifth G-CSF dose without increasing the daily dose will not be classified as dose escalation. |
| Proportion of Donors Requiring Plerixafor Rescue Mobilization | From the first G-CSF dose through completion of the final apheresis session, typically within 2 days and up to 3 consecutive days of apheresis. | Proportion of donors receiving plerixafor rescue mobilization because of inadequate peripheral blood CD34+ mobilization or insufficient collection yield, according to prespecified rescue criteria. |
| Peripheral Blood CD34+ Cell Count 12 Hours After the Third G-CSF Dose | 12 (±1) hours after the third G-CSF dose, before the first apheresis session. | Peripheral blood CD34+ cell count (cells/μL) measured 12 (±1) hours after the third G-CSF dose, before any apheresis procedure. CD34+ cells will be enumerated using standardized flow cytometry procedures. |
| Time to Neutrophil Engraftment After Transplantation | From transplantation (Day 0) through Day 100 after transplantation. | Time from stem cell infusion to neutrophil engraftment in transplant recipients, defined as the first of three consecutive days with an absolute neutrophil count ≥0.5 × 10⁹/L. Death before engraftment will be treated as a competing event in exploratory analyses. |
| Time to Platelet Engraftment After Transplantation | From transplantation (Day 0) through Day 100 after transplantation. | Time from stem cell infusion to platelet engraftment in transplant recipients, defined as the first of seven consecutive days with a platelet count ≥20 × 10⁹/L without platelet transfusion during the preceding seven days. Death before engraftment will be treated as a competing event. |
| Cumulative Incidence of De Novo Grade II-IV and III-IV Acute Graft-versus-Host Disease | From transplantation (Day 0) through Day 100 after transplantation. | Cumulative incidence of newly occurring grade II-IV and grade III-IV acute graft-versus-host disease (aGVHD) among transplant recipients, assessed using prespecified standard grading criteria. Competing events will be handled using competing-risk methods. |
| Total Number of Apheresis Sessions per Donor | From the first apheresis session through completion of the final apheresis session, typically within 2 consecutive days and up to 3 consecutive days. | Total number of apheresis sessions performed for each donor during the mobilization and collection period. |
| Incidence of Adverse Events in Healthy Donors | From the first G-CSF dose through 30 days after the final apheresis session. | Incidence and severity of adverse events associated with G-CSF mobilization, apheresis procedures, and rescue mobilization, including bone pain, headache, fatigue, citrate-related reactions, and vascular access complications. Adverse events will be assessed according to the protocol-specified grading system. |
Countries
China
Contacts
CONTACTHengwei Wu, MD
Outcome results
None listed