Pediatric Cancer, Solid Tumor Cancer
Conditions
Brief summary
Pediatric malignant solid tumors (including neuroblastoma, Wilms tumor, hepatoblastoma, rhabdomyosarcoma, osteosarcoma, Ewing sarcoma, and germ cell tumors) account for approximately 60% of childhood malignancies. Despite multimodal therapy, children with relapsed or refractory disease have poor outcomes. Repeated lines of intensive salvage chemotherapy cause cumulative damage to the hematopoietic system, resulting in profound and prolonged myelosuppression (absolute neutrophil count \<0.5×10\^9/L or platelet count \<20×10\^9/L) that often fails to recover despite standard supportive care with short-acting recombinant human granulocyte colony-stimulating factor (rhG-CSF) and recombinant human thrombopoietin (rhTPO). This leads to chemotherapy delays that compromise treatment continuity and intensity. Umbilical cord blood (UCB) contains hematopoietic progenitor cells, NK cells, T lymphocytes, and various hematopoietic and immunomodulatory factors. UCB infusion has been shown to accelerate hematopoietic recovery after chemotherapy and may enhance anti-tumor immune function. This is a single-center, single-arm, prospective exploratory study. Approximately 10 children (aged 1-18 years) with relapsed or refractory malignant solid tumors who develop severe post-chemotherapy myelosuppression with delayed hematopoietic recovery (persistent ANC \<1.0×10\^9/L and platelets \<50×10\^9/L despite ≥7 days of rhG-CSF/rhTPO support, resulting in chemotherapy delay) will receive UCB infusion in addition to continuing background anti-tumor therapy and standardized hematopoietic supportive care. Each patient may receive up to 3 UCB infusions. The follow-up period is 12 weeks from the first infusion. The study aims to: (1) evaluate the effect of UCB infusion on promoting hematopoietic recovery and on-schedule chemotherapy completion (compared with institutional historical controls); (2) evaluate immune reconstitution after UCB infusion, including dynamics of T-lymphocyte subsets, NK cells, B cells, and serum cytokines; (3) assess the safety of UCB infusion; and (4) explore differences in hematopoietic recovery and immune reconstitution across tumor types and treatment backgrounds.
Interventions
OTHERumbilical cord blood
Cryopreserved umbilical cord blood unit(s) selected by Tianjin Cord Blood Hematopoietic Stem Cell Bank (HLA-A, -B, -C, -DRB1, -DQB1 ≤5/10 match acceptable; ABO and Rh(D) compatible; TNC ≥1.5×10\^7/kg body weight). The unit is thawed in a 37-40°C water bath and infused intravenously over approximately 30 minutes with premedication (diphenhydramine and acetaminophen; dexamethasone if indicated) and continuous vital-sign monitoring. Each patient may receive up to 3 infusions, with an interval of ≥21 days between infusions.
Sponsors
Tianjin Medical University Cancer Institute and Hospital
Institute of Hematology & Blood Diseases Hospital, China
Union Stem Cell & Gene Engineering Co
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
0 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
1. Age 1-18 years, any sex; 2. Histopathologically confirmed pediatric malignant solid tumor (including but not limited to neuroblastoma, Wilms tumor, hepatoblastoma, rhabdomyosarcoma, osteosarcoma, Ewing sarcoma, and germ cell tumors), assessed by the investigator as high-risk, relapsed, or refractory; 3. In relapsed or refractory status requiring salvage chemotherapy; 4. Severe myelosuppression after the most recent chemotherapy cycle, meeting at least one of the following: ANC \<0.5×10\^9/L or platelet count \<20×10\^9/L; AND persistent ANC \<1.0×10\^9/L and platelets \<50×10\^9/L despite ≥7 days of standard supportive care (short-acting rhG-CSF 5 μg/kg/day and rhTPO 300 U/kg/day), resulting in a delay of ≥3 days of the next chemotherapy cycle; 5. During the chemotherapy delay period, platelet count ≥20×10\^9/L (transfusion permitted) and hemoglobin ≥60 g/L (transfusion permitted) after standard supportive care; 6. Adequate major organ function: liver function (ALT/AST ≤2.5× ULN, total bilirubin ≤1.5× ULN); renal function (creatinine clearance ≥60 mL/min/1.73 m²); cardiac function (echocardiographic shortening fraction ≥28%); 7. ECOG performance status ≤2 (or Lansky play-performance score ≥50%); 8. Expected survival ≥12 weeks; 9. The guardian fully understands the study and voluntarily signs the informed consent form, agreeing to the patient's completion of immune function monitoring (peripheral blood lymphocyte subsets, NK cells, and serum cytokines); age-appropriate assent is obtained from the child (oral assent with an illustrated assent form for ages 8-12 years; written assent with an adolescent assent form for ages 12-18 years); 10. For repeat infusions: the patient remains in relapsed/refractory status requiring continued chemotherapy and again meets the myelosuppression criterion in item 4.
Exclusion criteria
1. Progressive disease (PD) with investigator judgment that the patient is not suitable for continued chemotherapy; 2. Concurrent second primary malignancy or prior history of other malignancies; 3. Any active autoimmune disease or history of autoimmune disease; 4. Current use of immunosuppressants, or systemic glucocorticoid therapy for immunosuppressive purposes (physiologic replacement therapy excepted), continued within 2 weeks before enrollment; 5. Known allergy to umbilical cord blood components or history of severe transfusion-related adverse reactions; 6. Active, uncontrolled infection requiring intravenous anti-infective therapy for more than 72 hours without control; 7. Known history of psychotropic drug abuse; 8. Any other condition judged by the investigator that could lead to forced early termination of the study, such as other serious diseases (including psychiatric disorders) requiring concomitant treatment, severe laboratory abnormalities, or family/social factors affecting the safety of the participant or the integrity of study data.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite Primary Endpoint Achievement Rate | Within 21 days after each UCB infusion (up to 12 weeks from first infusion) | Proportion of UCB infusions for which all three of the following criteria are met: (1) on-schedule completion of the next chemotherapy cycle (delay ≤3 days); (2) ANC recovery to ≥1.0×10\^9/L sustained for ≥3 days within 21 days after infusion; (3) platelet recovery to ≥50×10\^9/L with platelet-transfusion independence for ≥7 days within 21 days after infusion. Each infusion is evaluated as an independent event, and the best response per patient is recorded. Results are described in comparison with institutional historical controls (on-schedule chemotherapy completion rate approximately 30%-40%). |
| On-schedule Chemotherapy Completion Rate | From each UCB infusion to the next scheduled chemotherapy cycle (up to 12 weeks from first infusion) | Proportion of UCB infusions after which the patient successfully receives the next chemotherapy cycle on the scheduled date (per the background regimen); the actual interval (days) from UCB infusion to the next chemotherapy cycle is recorded. |
| Time to ANC Recovery | Up to 21 days after each UCB infusion (up to 12 weeks from first infusion) | Number of days from each UCB infusion to ANC ≥1.0×10\^9/L sustained for ≥3 days. |
| Time to Platelet Recovery | Up to 21 days after each UCB infusion (up to 12 weeks from first infusion) | Number of days from each UCB infusion to platelet count ≥50×10\^9/L with platelet-transfusion independence for ≥7 days. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with Grade ≥3 hematologic laboratory abnormalities, assessed by NCI-CTCAE v5.0 | Baseline and Days 1, 3, 5, 7, 10, 14 after each infusion | WBC, ANC, hemoglobin, and platelet results collected at baseline and on Days 1, 3, 5, 7, 10, and 14 after each infusion will be graded according to NCI-CTCAE v5.0. The number and percentage of participants with Grade ≥3 hematologic laboratory abnormalities will be reported. |
| Absolute counts and percentages of lymphocyte subsets (CD3+, CD4+, CD8+ T cells, CD16+CD56+ NK cells, CD19+ B cells, and CD4+CD25+FoxP3+ regulatory T cells), measured by multiparameter flow cytometry | Baseline, Day 14, and Day 28 after each infusion | Peripheral blood will be collected at baseline (before each cord blood infusion) and on Days 14 and 28 after each infusion. Lymphocyte subsets will be identified and quantified by multiparameter flow cytometry, including CD3+, CD4+, and CD8+ T cells (with the CD4+/CD8+ ratio), NK cells (CD16+CD56+), B cells (CD19+), and regulatory T cells (CD4+CD25+FoxP3+). Each subset will be reported separately: absolute counts (cells/µL) and percentages among lymphocytes (%) will be summarized at each time point using descriptive statistics (mean ± SD or median \[IQR\]), and changes from baseline will be compared by paired t-test or Wilcoxon signed-rank test. |
| Serum Cytokine Levels | Baseline, Day 14, and Day 28 after each infusion | — |
| Number of units of red blood cells transfused after cord blood infusion | 2 weeks after each infusion | Red blood cell transfusion records will be reviewed within 2 weeks after each cord blood infusion. The volume of red blood cell transfusion (in units) will be recorded for each infusion and summarized per participant using descriptive statistics (mean ± SD or median \[IQR\]). Post-infusion transfusion requirements will be compared with the participant's own pre-infusion/historical data using Wilcoxon signed-rank test. |
| Number of platelet concentrate transfusions after cord blood infusion | 2 weeks after each infusion | Platelet transfusion records will be reviewed within 2 weeks after each cord blood infusion. The number of platelet concentrate transfusions (in bags) will be recorded for each infusion and summarized per participant using descriptive statistics (mean ± SD or median \[IQR\]). Post-infusion transfusion requirements will be compared with the participant's own pre-infusion/historical data using Wilcoxon signed-rank test. |
| Infection Incidence | 2 weeks after each infusion | — |
| Percentage of donor chimerism, assessed by short tandem repeat (STR) analysis | Day 14 after each infusion (plus Days 28 and 56 if chimerism >5%) | Peripheral blood will be collected on Day 14 after each cord blood infusion, and donor chimerism will be quantified by short tandem repeat (STR) analysis against the pre-infusion recipient baseline STR profile and the cord blood donor reference profile. The percentage of donor-derived cells will be reported for each infusion. If donor chimerism exceeds 5%, chimerism testing will be repeated on Days 28 and 56 after that infusion. Results will be summarized per participant using descriptive statistics (median \[range\]). |
| Incidence and Severity of Adverse Events (Cumulative Safety of Up to 3 Infusions) | From first infusion through 12 weeks of follow-up | — |
| Use of Hematopoietic Growth Factors (rhG-CSF/rhTPO) | Up to 12 weeks from first infusion | — |
Contacts
CONTACTYan Jin
Outcome results
None listed