This clinical trial investigates the safety, side effects, and effectiveness of combining an immunotherapy drug called dinutuximab-beta with standard induction chemotherapy for patients newly diagnosed with high-risk neuroblastoma. Dinutuximab-beta is an antibody designed to target specific molecules on the surface of neuroblastoma cells. In this pilot study, enrolled patients will receive dinutuximab-beta as a continuous intravenous infusion alongside a standard 6-cycle induction chemotherapy regimen. The primary goals of this study are to monitor how well patients tolerate the new combination treatment closely and to determine how effectively tumors shrink before patients proceed to the next phase of their standard consolidation therapy.
This is a prospective, single-arm, pilot study aiming to evaluate the tolerability, safety, and clinical efficacy of incorporating GD2-directed immunotherapy (Dinutuximab-beta) into the frontline induction chemotherapy for high-risk neuroblastoma. Patients with newly diagnosed high-risk neuroblastoma will receive Dinutuximab-beta administered as a 10-day continuous intravenous infusion (10 mg/m²/day) during Cycles 2 to 6 of the standard 6-cycle induction chemotherapy. The chemotherapy backbone includes cyclophosphamide, vincristine, doxorubicin/epirubicin, etoposide, and cisplatin. The study is designed with a safety monitoring phase for the initial cohort to evaluate unacceptable toxicities closely. Following the completion of the 6-cycle induction therapy, patients will be assessed for clinical response based on the revised International Neuroblastoma Response Criteria (INRC) before proceeding to standard consolidation therapy, which includes high-dose chemotherapy with stem cell rescue, radiotherapy, and maintenance therapy. Exploratory evaluations will also be conducted to monitor minimal residual disease (MRD), assess event-free and overall survival, and explore the correlation between immune biomarkers and clinical outcomes.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Dinutuximab-beta 10 mg/m²/day administered as a continuous intravenous infusion on Days 0-9 of Cycles 2-6.
Six cycles of standard induction chemotherapy consisting of cyclophosphamide, vincristine, doxorubicin (or epirubicin), etoposide, and cisplatin administered according to the study treatment schedule.
National Taiwan University Hospital
Taipei, Taiwan, Taiwan
Chang Gung Memorial Hospital Linkou Branch
Taoyuan, Taiwan, Taiwan
Number of Participants with Unacceptable Toxicities or Toxic Death
Tolerability is assessed by the number of toxic deaths and the number of patients experiencing unacceptable toxicities. Unacceptable toxicities are assessed according to CTCAE criteria and include: 1. toxicity requiring pressors for ≥ 24 hours (e.g., Grade 4 capillary leak syndrome, Grade 4 anaphylaxis/allergic reaction, or Grade 3-4 hypotension), 2. toxicity requiring ventilatory support for \> 24 hours, 3. Grade 4 or unresolved Grade 3 peripheral motor/sensory neuropathy, 4. Grade 4 acute infusion reaction.
Time frame: During Cycles 2-6 of induction therapy (up to approximately 6 months).
Clinical Response Rate (RR)
Clinical response rate is defined as the percentage of eligible participants who achieve a Partial Response (PR) or better (e.g., Complete Response or Very Good Partial Response). The tumor response will be evaluated using the revised International Neuroblastoma Response Criteria (INRC).
Time frame: At the end of induction therapy (up to approximately 6 months).
Event-Free Survival (EFS)
Event-free survival (EFS) is defined as the time from the date of study enrollment to the occurrence of disease relapse or progression, secondary malignancy, or death.
Time frame: Up to 10 years from the date of study enrollment.
Overall Survival (OS)
Overall survival (OS) is defined as the time from the date of study enrollment to death from any cause. Patients without death will be censored at the time of last follow-up.
Time frame: Up to 10 years from the date of study enrollment.
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