The aim is to evaluate the outcome and safety of risk-stratification oriented treatment for pediatric Ewing sarcoma in multicenters .

Pediatric Ewing sarcoma is stratified into three risk groups(low risk, moderate risk and high risk) accordiong to age, longest diameter of lesion, volume and tumor site. Participants receive chemotherapy with corresponding intensity. The prospective study is to assess efficacy, outcome and safety profile of different treatment received for pediatric Ewing sarcoma.

The prospecitive single-arm study is to be conducted in Chinese multicenters.

Inclusion Criteria:

• age≤18 years, no gender limitation;
• The ECOG （performance status，PS）is 0～1 score;
• The expected survival time is not less than 12 weeks;
• Heart function: A) Cardiac COLOR ultrasound detection LVEF≥ 50%; B) EKG suggests no myocardial ischemia;C) No history of arrhythmia requiring drug intervention before enrollment;
• Patients who meet the clinical diagnostic criteria and are diagnosed with pediatric Ewing sarcoma;
• Patients who have progressed, relapsed or refractory after first-line treatment (failed to achieve complete or partial response after recent treatment);
• Measurable lesions (according to RECIST 1.1 standards, CT scan length of tumor lesions ≥10mm, CT scan short diameter of lymph node lesions ≥15mm, measurable lesions have not received radiotherapy, freezing and other local treatments);
• The patient must fully recover from the acute toxic effects of all previous anticancer chemotherapy: A) Myelosuppressive chemotherapy: at least 21 days after the last myelosuppressive chemotherapy (42 days if nitrosourea was used previously);B) Experimental drug or anticancer therapy other than chemotherapy: not available within the first 28 days of planned initiation of AI or VIT. Complete recovery from clinically significant toxicity of the therapy must be determined;C) Hematopoietic growth factor: 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;D) Immunotherapy: at least 42 days after completion of any type of immunotherapy (except steroids), such as immune checkpoint inhibitors and tumor vaccines; E) X-ray therapy (XRT) : at least 14 days after local palliative XRT (small mouth); For other substantial bone marrow (BM) irradiation, it must be completed for at least 42 days; F) Stem cell infusion without total body irradiation (TBI) : there is no evidence of active graft-versus-host disease and the transplant or stem cell infusion must be completed at least 56 days after the infusion;
• Laboratory tests during screening should meet the following conditions: A) Absolute value of neutrophils (ANC) ≥1.5×109/L (if bone marrow invasion, ANC≥1.0×109/L); B) Platelet count (PLT) ≥75×109/L (PLT≥50×109/L for bone marrow invasion); C) Bilirubin (sum of combined + uncombined) ≤ 2.5× upper limit of normal value (ULN) (corresponding to age), patients with confirmed Gilbert's syndrome can be included in the group according to the investigator's judgment; D) Estimated glomerular filtration rate ≥30 mL/min/1.73 m2 or serum creatinine (Cr) ≤ 1.5ULN (calculated according to the standard Cockcroft-Gault formula); E) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5×ULN (5 times ULN if liver metastasis is present)
• Able to comply with outpatient treatment, laboratory monitoring and necessary clinical visits during the study period;
• The parent/guardian of the child or adolescent subject is capable of understanding, agreeing to, and signing the study Informed consent (ICF) and the applicable child consent form prior to initiating any program-related procedures; Subject is capable of expressing consent with parental/guardian consent (if applicable).

Exclusion Criteria:

• Exclusion criteria

  • Patients who have symptomatic brain metastasis except that who completed therapy 21 days prior to enrollment and had stable disease related to brain metastasis confirmed by cerebral CT or MRI or radiography;
  • Previous or concurrent clinical significance of active cardiovascular diseases, including congenital heart disease or pericardial disease, history of heart failure, myocardial infarction, coronary heart disease, heart valvular disease, cardiomyopathy, arrhythmias (including persistent atrial fibrillation, complete left bundle branch block, frequent ventricular premature onset); Or prolonged QT interval (QTc) after current corrected heart rate > 480 ms; Patients with grade III ~ IV cardiac insufficiency according to the New York Heart Association (NYHA) cardiac function classification (age > 3 years) or infant cardiac function standard (age ≤3 years), or left ventricular ejection fraction (LVEF) < 50% as indicated by color doppler echocardiography;
  • Patients with a history of pulmonary interstitial disease or concurrent pulmonary interstitial disease;
  • Abnormal coagulation function (INR>1.5 or prothrombin time (PT)>ULN+4 seconds or APTT>1.5 ULN), with a tendency to bleed or undergoing thrombolytic or anticoagulant treatment;
  • Severe chronic skin diseases in the past;
  • Previous allergic asthma or severe allergic disease;
  • Poorly controlled hypertension and diabetes;
  • Have a history of other tumors;
  • HIV or syphilis infected patients;
  • Patients who have previously received organ transplants;
  • Uncontrolled and active systemic bacterial, viral or fungal infection;
  • Contraindications to the use of large doses of hormones, such as uncontrolled hyperglycemia, gastric ulcers or mental diseases;
  • Have a history of severe neurological or psychiatric disorders, including epilepsy or autism.