Pilot Study of Umbilical Cord Blood Natural Killer (NK) Cell Therapy for Pediatric Neuroblastoma.
Neuroblastoma is the most common extracranial solid tumor, with more than half of the patients diagnosed at the metastatic stage, classified as high-risk. High-risk neuroblastoma has a poor prognosis and low survival rate. Despite treatment with induction, consolidation, and maintenance therapy including GD2 monoclonal antibody, the survival rate is only about 60%, and many patients still relapse, progress, and die. NK cell therapy is an emerging immunotherapy that can effectively inhibit and kill tumor cells without significant adverse reactions, reducing the risk of tumor recurrence and metastasis, and improving patients' immunity and quality of life. Its safety has been widely recognized. Currently, clinical trials of NK cell infusion therapy for neuroblastoma patients are ongoing, and NK cell-based immunotherapy holds great clinical promise for neuroblastoma. We plan to conduct a phase I clinical trial on umbilical cord blood NK cell therapy in combination with other treatments (GD2 antibody, chemotherpay, etc) for high-risk, recurrent/refractory neuroblastoma in children to determine the maximum tolerated dose of umbilical cord blood NK cell therapy in these patients, thereby laying the foundation for future combination therapies and phase II and III clinical studies.
• All of the following criteria must be met in order to be eligible for this trial:
• Agree to participate in the trial and sign a written informed consent form;
• Age ≤18 years, gender not limited;
• Karnofsky (≥16 years old) or Lansky (\<16 years old) physical status score (Appendix II) of at least 50;
• Patients diagnosed with high-risk, recurrent/refractory neuroblastoma in children according to clinical diagnostic criteria, who have undergone comprehensive treatment (surgery, chemotherapy, radiotherapy ± stem cell transplantation ± GD2 monoclonal antibody therapy);
• Expected survival period of at least 12 weeks;
• The patient must have fully recovered from the acute toxic effects of all previous anticancer chemotherapy, such as recovery to grade I after bone marrow suppression;
• Bone marrow suppressive chemotherapy: At least 21 days after the last bone marrow suppressive chemotherapy (if nitrosoureas were used previously, then 42 days);
• Investigational drugs or anticancer therapies other than chemotherapy: Must not be used within 28 days before the planned start of NK cell immunotherapy. Full recovery from the clinically significant toxicity of that therapy must be confirmed;
• Hematopoietic growth factors: At least 14 days after the last dose of long-acting growth factors or 3 days after the last dose of short-acting growth factors;
⁃ X-ray therapy (XRT): At least 14 days after local palliative XRT (small field port); if other substantial bone marrow (BM) irradiation is involved, including prior radioactive iodine metaiodobenzylguanidine (131I-MIBG) treatment, it must end at least 42 days ago;
⁃ Stem cell infusion without total body irradiation (TBI): No active graft-versus-host disease, must have ended at least 56 days after transplantation or stem cell infusion;
⁃ Laboratory tests during the screening period must meet the following conditions:
∙ Absolute neutrophil count (ANC) ≥1.0×10\^9/L (if bone marrow involvement, then ANC ≥0.5×10\^9/L)
‣ Platelet count (PLT) ≥75×10\^9/L (if bone marrow involvement, then PLT ≥20×10\^9/L)
‣ Bilirubin ≤1.5 times the upper limit of normal (ULN)
‣ Creatinine ≤1.5 times ULN (calculated using the standard Cockcroft-Gault formula)
‣ ALT/AST ≤3 times ULN (if there is liver metastasis, this can be relaxed to 5 times ULN)
⁃ During the study period, able to comply with outpatient treatment, laboratory monitoring, and necessary clinical visits; parents/guardians of pediatric or adolescent participants are capable of understanding, consenting to, and signing the informed consent form (ICF) and applicable child assent forms before initiating any protocol-related procedures; with parental/guardian consent, the participant is capable of expressing their consent (when applicable).