Pilot Study of Combining of Dinutuximab-β With Induction Chemotherapy in Newly Diagnosed High Risk Neuroblastoma
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Number of Participants with Unacceptable Toxicities or Toxic Death
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Year 至 30 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Must be 1 to 30 years of age at the time of initial diagnosis.
- •Must have histological verification of neuroblastoma or ganglioneuroblastoma, OR demonstration of neuroblastoma cells in the bone marrow with elevated urinary VMA at the time of initial diagnosis.
- •Must have newly diagnosed high-risk neuroblastoma according to the revised COG NBL risk classifier (version 2), defined as meeting at least ONE of the following:
- •INRG Stage M: MYCN amplification (> 4-fold increase), OR age 12 to < 18 months without MYCN amplification but with unfavorable histology/DI = 1/SCA, OR age > 18 months regardless of biologic features.
- •INRG Stage MS: MYCN amplification, OR age 12 to < 18 months without MYCN amplification but with unfavorable histology/DI = 1/SCA.
- •INRG Stage L2: MYCN amplification, OR age 18 months to < 5 years without MYCN amplification but with unfavorable histology, OR age ≥ 5 years without MYCN amplification but with unfavorable histology (undifferentiated or poorly differentiated tumor).
- •INRG Stage L1: Tumor with incomplete resection and MYCN amplification.
- •Patients > 18 months of age initially diagnosed with INRG Stage L1, L2, or MS who are subsequently upgraded to high-risk disease.
- •Must have had no prior systemic therapy, or have only completed the first cycle of induction chemotherapy under the TPOG N2020-HR protocol.
- •Must have measurable disease, defined as at least ONE of the following (Note: Patients with elevated VMA only are NOT eligible):
- •Measurable tumor on MRI or CT scan within 3 weeks prior to study entry (≥ 10 mm in at least one dimension) that is MIBG avid or demonstrates increased FDG/FDOPA uptake on PET scan.
- •MIBG or FDG/FDOPA PET scan within 2 weeks prior to study entry with positive uptake at a minimum of one site.
- •ECOG Performance Status of 0, 1, or
- •Adequate organ function, including:
- •Renal: Creatinine clearance or estimated GFR ≥ 60 mL/min/1.73 m², or serum creatinine ≤ upper limit of normal (ULN) based on age/gender.
- •Liver: Total bilirubin ≤ 1.5 x ULN for age AND SGPT (ALT) ≤ 5.0 x ULN (if liver tumor is present) or ≤ 3.0 x ULN (if no liver tumor).
- •CNS: No clinical or radiological evidence of active CNS disease (well-controlled seizures allowed), and CNS toxicity ≤ Grade
- •Cardiac: Shortening fraction ≥ 27% or Ejection fraction ≥ 50% by ECHO or gated radionuclide study.
- •Pulmonary: No dyspnea at rest, no exercise intolerance, no chronic oxygen requirement, and room air pulse oximetry > 94%.
- •Must be enrolled on the TPOG N2020-GD2 protocol with completed informed consent forms, and be willing to proceed to standard therapy of high-risk neuroblastoma with a 10-year follow-up.
排除标准
- •Participation in other interventional clinical trials within 1 month.
- •Inability to obey the trial instructions.
- •Patients with bone marrow failure syndromes.
- •Current requirement for immunosuppressive medications (e.g., tacrolimus, cyclosporine, systemic corticosteroids for reasons other than prevention/treatment of acute allergic reactions or adrenal replacement therapy).
- •Females who are pregnant or breastfeeding (A pregnancy test is required for female patients of childbearing potential).
- •Female patients who are pregnant are ineligible since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential.
- •Lactating females who plan to breastfeed their infants.
- •The subject or their partner is planning to conceive
- •Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method during study therapy and for two months after the last dose of (ch14.18/CHO) (dinutuximab-β) are not eligible.
结局指标
主要结局
Number of Participants with Unacceptable Toxicities or Toxic Death
时间窗: During Cycles 2-6 of induction therapy (up to approximately 6 months).
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.
Clinical Response Rate (RR)
时间窗: At the end of induction therapy (up to approximately 6 months).
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).
次要结局
- Event-Free Survival (EFS)(Up to 10 years from the date of study enrollment.)
- Overall Survival (OS)(Up to 10 years from the date of study enrollment.)
研究者
CHEN, SHIH-HSIANG
M.D., Pediatric Hematology/Oncology
Chang Gung Memorial Hospital