A Pivotal Phase 2 Trial of Antibody Naxitamab (hu3F8) and Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) in High-Risk Neuroblastoma Patients With Primary Refractory Disease or Incomplete Response to Salvage Treatment in Bone and/or Bone Marrow
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 122
- 试验地点
- 39
- 主要终点
- Response rate during Naxitamab treatment
研究概览
简要总结
Children and adults diagnosed with high-risk neuroblastoma patients with primary refractory disease or incomplete response to salvage treatment in bone and/or bone marrow will be treated for up to 101 weeks with naxitamab and granulocyte-macrophage colony stimulating factor (GM-CSF). Patients will be followed for up to five years after first dose.
Naxitamab, also known as hu3F8 is a humanised monoclonal antibody targeting GD2
详细描述
Each patient will receive treatment for up to 101 weeks following the first Naxitamab administration. After the end of trial visit, each patient will enter a long-term follow-up where they will be monitored for up to 5 years after first treatment cycle.
Each investigational cycle is started with 5 days, days -4 to 0, of Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) administered at 250 µg/m2/day in advance of the start of Naxitamab administration. GM-CSF is thereafter administered at 500 µg/m2/day on days 1 to 5. As standard treatment, Naxitamab is administered at 3 mg/kg/day on days 1, 3, and 5, totalling 9 mg/kg per cycle.
Treatment cycles are repeated every 4 weeks (±1 week) until complete response or partial response followed by 5 additional cycles every 4 weeks (±1 week). Subsequent cycles are repeated every 8 weeks (±2 weeks) through 101 weeks from first infusion at the discretion of the investigator. End of treatment will take place around 8 weeks after the last cycle and thereafter long-term follow-up will continue.
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 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of neuroblastoma as defined per International Neuroblastoma Response Criteria
- •High-risk neuroblastoma patients with either primary refractory disease or incomplete response to salvage treatment (in both cases including stable disease, minor response and partial response) evaluable in bone and/or bone marrow.
- •Life expectancy ≥ 6 months
排除标准
- •Any systemic anti-cancer therapy, including chemotherapy or immunotherapy, within 3 weeks before 1st dose of GM-CSF
- •Evaluable neuroblastoma outside bone and bone marrow
- •Existing major organ dysfunction > Grade 2, with the exception of hearing loss, hematological status, kidney and liver function
- •Active life-threatening infection
研究组 & 干预措施
GM-CSF + Naxitamab
Each investigational cycle is started with 5 days of GM-CSF administered at 250 µg/m2/day in advance of the start of Naxitamab administration. GM-CSF is thereafter administered at 500 µg/m2/day on days 1 to 5. As standard treatment, Naxitamab is administered at 3 mg/kg/day on days 1, 3, and 5 totalling 9 mg/kg per cycle. Treatment cycles are repeated every 4 weeks until CR or PR followed by 5 additional cycles every 4 weeks (±1 week). Subsequent cycles are repeated every 8 weeks (±2 weeks) through 101 weeks from first infusion at the discretion of the investigator. After end of treatment patients will enter a long-term follow up for up to 3 years after end of treatment visit.
干预措施: GM-CSF + Naxitamab (Biological)
结局指标
主要结局
Response rate during Naxitamab treatment
时间窗: 101 weeks
Overall objective response rate (ORR) during the Naxitamab treatment period that will be centrally assessed according to the International Neuroblastoma Response Criteria (INRC) modified with 123I-MIBG criteria and following the use of 18F FDG-PET for MIBG non-avid lesions.
次要结局
- Assessment of the Area under the Curve (AUC) of naxitamab(Pre-naxitamab dose - 552 hours)
- Assessment of the terminal half-life (t½) of naxitamab(Pre-naxitamab dose - 552 hours)
- Assessment of anti-drug antibody (ADA) formation(Pre-naxitamab dose - 552 hours)
- Safety of patients with positive human anti-drug antibody (ADA)(101 weeks)
- Number of infusions done in an outpatient setting(101 weeks)
- Percentage of infusions done in an outpatient setting(101 weeks)
- Overall Survival(5 years)
- Happiness and activity levels(39 days)
- Incidence of adverse events and serious adverse events in ADA positive patients(101 weeks)
- Assessment of the clearance of naxitamab(Pre-naxitamab dose - 552 hours)
- Complete Response Rate(101 weeks)
- Progression Free Survival (PFS)(5 years)
- Duration of Response (DoR)(101 weeks)
- Assessment of the maximum serum concentration (cmax) of naxitamab(Pre-naxitamab dose - 552 hours)
- Assessment of the minimum serum concentration (cmin) of naxitamab(Pre-naxitamab dose - 552 hours)
- Incidence of adverse events and serious adverse events(101 weeks)
- Intravenous (IV) opioid use (cycle 1)(6 hours)
- Hospitalization days (cycle 1)(4 weeks)
- Assessment of the volume of distribution of naxitamab(Pre-naxitamab dose - 552 hours)
- Intravenous (IV) opioid use (all cycles)(101 weeks)