Phase II Study of Chidamide-Dinutuximab Beta-Irinotecan-Temozolomide for Refractory/Relapsed Neuroblastoma in Children

Inclusion criteria

• 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.

Exclusion criteria

• Patients with CTCAE v5.0 Grade 3 or higher toxicities involving hearing impairment, hematologic disorders, hepatic, or renal diseases.
• Patients with CTCAE v5.0 Grade 2 or higher neurotoxicity.
• Major surgical procedure within 14 days prior to the first dose of the study drug.
• Severe infection (requiring IV antibiotics, antifungals, or antivirals) within one week prior to treatment, or unexplained fever >38.5°C during screening or before the first dose.
• Congenital or acquired immunodeficiency, or active infectious diseases such as HIV or active hepatitis (with transaminase levels not meeting inclusion criteria; HBV DNA ≥1000 IU/mL; HCV RNA ≥1000 IU/mL). Chronic HBV carriers with HBV DNA <2000 IU/mL may be enrolled if they receive concurrent antiviral therapy during the trial.
• Any concomitant condition that, in the investigator's judgment, seriously jeopardizes patient safety, may confound the study results, or could impede the patient's completion of the study.