Pediatric malignant tumors
Conditions
Interventions
Case series:Patients were enrolled by the design of phase I study standard. Sindilimab was divided into three dose levels: 1 mg / kg, 3 mg / kg, and 10 mg / kg. Dose escalation was carried out from th
Sponsors
Cancer center of Sun Yat sen University
Eligibility
Sex/Gender
All
Age
1 Years to 18 Years
Inclusion criteria
Inclusion criteria: 1. Patients aged 1-18 years; 2. ECoG PS score: 0-1; 3. Patients with children's malignant tumors confirmed by histopathology, including Hodgkin's lymphoma, mediastinal large B-cell lymphoma, NK / T-cell lymphoma, nasopharyngeal carcinoma, malignant melanoma, neuroblastoma, hepatoblastoma, sarcoma, brain tumor, etc; 4. Advanced patients who failed to receive standard treatment; 5. Patients who must have at least one measurable lesion defined by RECIST or who standard; 6. Patients with estimated survival time >=6 months; 7. Heart function: (1) LVEF >=50% by color Doppler echocardiography; (2) EKG showed no myocardial ischemia; (3) There was no history of arrhythmia requiring drug intervention before admission; 8. Patients must completely recover from the acute toxicity of all previous anticancer chemotherapy; (1) Myelosuppression chemotherapy: at least 21 days after the last myelosuppression chemotherapy (42 days if nitrosourea was used in the earlier stage); (2) Experimental drug or anti-cancer therapy other than chemotherapy: it can not be used within the first 28 days before the planned start of the use of cindilimab, and must be clearly recovered from the clinically significant toxicity of the therapy; (3) Immunotherapy: at least 42 days after completion of any type of immunotherapy (excluding steroids), including immunocheckpoint inhibitors and tumor vaccines; (4) X-ray therapy (XRT): at least 14 days after local palliative XRT (small oral area); in case of other substantial bone marrow (BM) irradiation, including pre radioiodinated m-iodobenzidine (131I-MIBG) treatment, at least 42 days must be ended; (5) Stem cell infusion without total body irradiation (TBI): there is no evidence of active graft-versus-host disease. At least 56 days must elapse after transplantation or stem cell infusion; 9. Patients who have previously received CTLA-4 antibody must meet the following conditions to be admitted to the group: (1) More than 12 weeks after the last administration; (2) There was no history of serious immune related adverse events (CTCAE v4.03 G3 or G4); 10. For patients who have known no BM involvement: (1) Neutrophil absolute count (ANC) >=1.0x10^9 / L; (2) Platelet count >=100.0x10^9/L; (3) Hemoglobin >=90 g/L; 11. Liver and kidney function should meet the following standards: (1) Bilirubin (sum of combined and unconjugated) is less than 2.5 ULN (corresponding to age). Patients who have been confirmed as Gilbert's syndrome can be judged whether to enter the group according to the researchers; (2) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were less than 2.5 ULN; (3) Estimated glomerular filtration rate >=30 ml / min / 1.73 m2 or serum creatinine (CR) < 1.5 ULN; 12. Patients who are able to follow outpatient treatment, laboratory monitoring and necessary clinical visits during the study; 13. The parents / guardians of the child or adolescent subjects have the ability to understand, agree and sign the study informed consent form (ICF) and the applicable child consent form before initiating any program related procedures; the subjects have the ability to express their consent (when applicable) with the consent of the parents / guardians.
Exclusion criteria
Exclusion criteria: 1. Patients who have received targeted drugs of anti-PD-1 or anti-PD-L1 monoclonal antibody or related pathway; 2. Patients who are known to be allergic to monoclonal antibody PD-1 or any of its adjuvants; patients who have a history of allergic diseases or have severe allergic constitution; 3. Patients suffering from other malignant tumor diseases other than those treated by the Institute, except: cured malignant tumors that did not recur within 3 years before the study was selected, completely resected basal cell and squamous cell skin cancer, and completely resected carcinoma in situ of any type; 4. Patients with active central nervous system metastasis (whether or not treated), including symptomatic brain metastasis or meningeal metastasis or spinal cord compression, etc.; except: asymptomatic brain metastasis (no progress within at least 4 weeks after radiotherapy and / or no neurosis or signs after surgical resection, no dexamethasone or mannitol treatment is required); 5. Uncontrollable patients with pleural effusion, pericardial effusion or ascites requiring repeated drainage; 6. The patients whose toxicity of previous treatment was still higher than grade 1 (CTCAE v4.03 standard), except for alopecia and neurotoxicity; 7. Patients with a history of mental disorders; 8. Patients with a history of drug use or drug abuse; 9. Patients with history of idiopathic pulmonary fibrosis or pneumonia; 10. Patients who need to be treated with immunosuppressive drugs, or need to use corticosteroids in whole or in part according to the dose with immunosuppressive effect (prednisone > 10 mg / day or equivalent dose of similar drugs). 11. Patients with a history of autoimmune diseases, including but not limited to systemic lupus erythematosus, psoriasis, rheumatoid arthritis, inflammatory bowel disease, Hashimoto's thyroiditis, etc., except: type I diabetes mellitus, hypothyroidism that can be controlled only by hormone replacement therapy, skin diseases (such as vitiligo and psoriasis) that do not need systemic treatment, and controlled celiac disease , or diseases that are not expected to recur if there is no external stimulus; 12. Patients with active tuberculosis infection in the past or at present; 13. Patients with active infection who need systemic treatment; 14. Uncontrolled hypertension (systolic blood pressure >=140 mmHg and / or diastolic blood pressure = 90) Patients with mmHg or pulmonary hypertension or unstable angina pectoris, myocardial infarction or bypass and stent operation within 6 months before administration, chronic heart failure history meeting the New York Heart Association (NYHA) standard grade 3-4, clinically significant valve disease, severe arrhythmias (except for atrial fibrillation and paroxysmal supraventricular tachycardia) requiring treatment, including men with QTc interval It was >=450 ms, female >=470 MS (calculated by fridericia formula), cerebrovascular accident (CVA) or transient ischemic attack (TIA) within 6 months before administration; 15. Patients with serious medical diseases, including but not limited to: uncontrolled diabetes, active peptic ulcer, active bleeding, etc; 16. The patients with anti HIV, TP AB, HCV AB positive, HBV Ag positive and HBV DNA copy number > the upper limit of normal value of detection unit; 17. Patients with abnormal thyroid function (FT3, FT4, T3, T4); 18. Patients expected to have major surgery within 28 days before administration or during treatment;
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| MTD; | — |
Secondary
| Measure | Time frame |
|---|---|
| Hematology and non-hematology toxicity (NCI CTCAE v5.0 );Objective presponse rate (ORR); | — |
Countries
China
Contacts
Public ContactYizhuo Zhang
Cancer center of Sun Yat sen University
Outcome results
None listed