Umbilical Cord Blood NK Cell Therapy for High-Risk Pediatric Soft Tissue Sarcoma: Efficacy and Safety Study

Inclusion criteria

To be eligible for the study, participants must meet all of the following criteria:

• Give informed consent and sign a written informed consent form.
• Age ≤ 18 years, no gender limitation.
• Karnofsky (≥16 years) or Lansky (<16 years) (Appendix 2) performance status score of at least 50 (Appendix 2).
• Diagnosis of high-risk and relapsed/refractory pediatric soft tissue sarcoma, confirmed by clinical criteria, and who have undergone prior comprehensive treatment (surgery, chemotherapy, radiation, and/or stem cell transplantation).
• Estimated survival time of at least 12 weeks.
• Complete recovery from all acute toxicities of prior anti-cancer chemotherapy, such as bone marrow suppression with recovery to grade I.
• Myelosuppressive chemotherapy: at least 21 days after the last myelosuppressive chemotherapy (42 days if prior use of nitrosourea).
• Experimental drugs or anti-cancer therapies other than chemotherapy: not used within 28 days prior to the planned start of NK cell immunotherapy. Must be fully recovered from the clinical significant toxicity of the therapy.
• Hematopoietic growth factors: at least 14 days after the last administration of long-acting growth factor or 3 days after the last administration of short-acting growth factor.
• X-ray therapy (XRT): at least 14 days after local palliative XRT (small field mouth) or at least 42 days after other substantive bone marrow (BM) irradiation, including prior radioactive iodine-131 meta-iodobenzylguanidine (131I-MIBG) treatment.
• Stem cell transplantation without whole-body irradiation (TBI): no evidence of active graft versus host disease (GvHD), and at least 56 days after transplantation or stem cell transplantation.
• Laboratory tests during the screening period must meet the following conditions:

Absolute neutrophil count (ANC) ≥ 1.0 × 10^9/L (ANC ≥ 0.5 × 10^9/L if bone marrow involvement).

Platelet count (PLT) ≥ 75 × 10^9/L (PLT ≥ 20 × 10^9/L if bone marrow involvement).

Bilirubin ≤ 1.5 times the upper limit of normal (ULN). Creatinine ≤ 1.5 times the ULN (calculated according to the standard Cockcroft-Gault formula).

ALT/AST ≤ 3 times the ULN (can be relaxed to 5 times the ULN if liver metastasis is present).

• Ability to comply with outpatient treatment, laboratory monitoring, and necessary clinical visits during the study. For pediatric or adolescent participants, the parent/guardian must be able to understand, consent, and sign the study informed consent form (ICF) and applicable child consent form before initiating any protocol-related procedures. The participant will be able to express their consent (where applicable) under the consent of the parent/guardian.

Exclusion criteria

Participants who meet any of the following criteria are not eligible for the study:

• Presence of symptomatic brain metastasis (patients with brain metastasis treated and symptomatically stable for at least 2 months before enrollment are eligible, but must be confirmed to have no cerebral hemorrhage symptoms by cranial brain MRI, CT, or venous contrast).
• History of or current cardiovascular disease, including ≥ II-grade myocardial ischemia or myocardial infarction, uncontrolled arrhythmia (including QTc interval ≥ 450 ms in men and ≥ 470 ms in women), or ≥ III-IV-grade heart failure according to the NYHA standard (Appendix 3) or left ventricular ejection fraction (LVEF) < 50% according to echocardiography.
• History of or current interstitial lung disease.
• Coagulation function abnormality (INR > 1.5 or prothrombin time (PT) > ULN + 4 seconds or APTT > 1.5 ULN), with bleeding tendency or receiving anticoagulation or thrombolytic therapy.
• Any venous or arterial thromboembolic event within 12 months prior to enrollment, including cerebrovascular accidents (including transient ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism.
• Known hereditary or acquired bleeding and thrombotic tendency (e.g., hemophiliacs, coagulation dysfunction, thrombocytopenia, splenomegaly).
• Long-term, untreated wounds or fractures (excluding pathologic fractures caused by tumor).
• Major surgery or severe traumatic injury, fracture, or ulcer within 4 weeks prior to enrollment.
• Factors that significantly affect the absorption of oral drugs, such as difficulty swallowing, chronic diarrhea, and intestinal obstruction.
• History of abdominal fistula, gastrointestinal perforation, or peritonitis within the past 6 months.
• Urinary routine showing ≥ ++ proteinuria, and confirmed 24-hour urine protein ≥ 1.0 g.
• Presence of symptomatic serous cavity effusion requiring treatment (including pleural effusion, ascites, pericardial effusion); note: asymptomatic serous cavity effusion can be enrolled, symptomatic serous cavity effusion can be enrolled after active symptomatic treatment (not using anti-cancer drugs for serous cavity effusion treatment), and eligible for enrollment according to the judgment of the researcher.
• Active infection requiring anti-microbial therapy (e.g., requiring the use of antibacterial drugs, antiviral drugs, but not including chronic hepatitis B anti-hepatitis B treatment, anti-fungal drug treatment).
• History of substance abuse of psychiatric drugs and inability to quit or with psychiatric disorders.
• Participation in other anti-tumor drug clinical trials within the past 4 weeks.
• Receiving systemic hormone treatment or other forms of immunosuppressive treatment within 2 weeks prior to the first dose of the study drug.
• History of active autoimmune disease requiring systemic treatment (e.g., using disease-modifying drugs, corticosteroids, or immunosuppressive agents) within the past 2 years; note: alternative treatment (e.g., thyroid hormone, insulin, or physiological corticosteroid replacement therapy for adrenal or pituitary dysfunction) is not considered systemic treatment.
• Contraindications for IL-2 use.
• Active infection requiring systemic venous treatment.
• Administration of live vaccines within 1 month prior to the first use of the study drug; live vaccines against seasonal influenza, injectable inactivated virus vaccines are allowed, but nasal administration of live attenuated influenza vaccines is not allowed.
• Prior or concurrent other untreated malignant tumors, excluding cured superficial basal cell carcinoma, cervical in situ carcinoma, and superficial bladder carcinoma.
• Other conditions judged by the researcher to potentially affect the conduct of the clinical research and the determination of research results.
• Viral screening during the screening period showing any of the following:

HBsAg positive and HBV DNA above the normal upper limit. Anti-HCV positive and HCV RNA positive. HIV positive.

• Prior allogeneic tissue/organe transplantation.
• Poor compliance, unable to cooperate with clinical research.