A Phase II Trial of Chidamide Combined With Dinutuximab Beta, Irinotecan, and Temozolomide for Refractory or Relapsed Neuroblastoma in Children
This is a Phase II clinical trial investigating the effectiveness and safety of a four-drug combination-Chidamide, Dinutuximab Beta, Irinotecan, and Temozolomide-for children with relapsed or refractory neuroblastoma. The primary goal is to evaluate how well this regimen works to control the cancer, while the secondary goal is to closely monitor its safety and side effects in these young patients.
• Patients with histologically diagnosed neuroblastoma, defined according to the International Neuroblastoma Risk Group (INRG) classification system or the Chinese expert consensus/guideline for pediatric neuroblastoma.
• Patients with relapsed or refractory neuroblastoma. Relapsed: any patient with recurrent neuroblastoma. Refractory: patients showing an inadequate response (partial response, minor response, or stable disease) to prior therapy, leading to progression.
• Prior treatment with epigenetic drugs (e.g., HDAC inhibitors, DNA methylation inhibitors) or GD2 monoclonal antibodies does not affect eligibility for this study.
• Presence of evaluable disease.
• Performance Status: Lansky score ≥50%, Karnofsky score ≥50%, or ECOG score ≤3.
• Life expectancy ≥12 weeks.
• Bone marrow function: Without bone marrow disease: Platelets ≥75×10⁹/L, Absolute Neutrophil Count (ANC) ≥0.75×10⁹/L, Hemoglobin ≥8 g/dL (transfusion allowed). With bone marrow disease: Platelets ≥50×10⁹/L, ANC ≥0.5×10⁹/L, Hemoglobin ≥8 g/dL (transfusion allowed).
• Renal function: No clinically significant proteinuria (morning urine dipstick \<2+). If proteinuria ≥2+ is detected, the protein-to-creatinine (Pr/Cr) ratio must be \<0.5 or 24-hour protein excretion must be \<0.5 g.
• Serum creatinine ≤1.5 × ULN; if higher, the calculated glomerular filtration rate (by radioisotope method) must be ≥60 mL/min/1.73 m².
⁃ Hepatic function: AST or ALT ≤2.5 × ULN and total bilirubin ≤1.5 × ULN. In the presence of liver metastases: AST or ALT ≤5 × ULN and total bilirubin ≤2.5 × ULN.
⁃ Cardiac function: Left ventricular shortening fraction ≥29% on echocardiogram.
⁃ Coagulation: For patients not on anticoagulation therapy: INR ≤1.5 and APTT ≤1.5 × ULN. Anticoagulation is allowed if INR or APTT is within the therapeutic range (per institutional standards) and the patient has been on a stable dose for at least two weeks prior to study enrollment.
⁃ Oxygen saturation \>94% on room air.
⁃ Ability to comply with the study visit schedule and other protocol requirements.