Phase II Study of Hu3F8, Irinotecan/Temozolomide and Sargramostim (HITS) Chemoimmunotherapy for High-Risk Neuroblastoma
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
研究概览
简要总结
The purpose of this study is to find out whether an experimental drug called Hu3F8 can be given with the chemotherapy drugs irinotecan and temozolomide and another drug called GM-CSF. The investigators want to find out if this combination is safe and what effect it has on the participant and the disease.
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
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of NB as defined by international criteria,.e., histopathology (confirmed by the MSK Department of Pathology) or bone marrow metastases plus high urine catecholamine levels
- •High-risk NB as defined as any of the following:
- •Stage 4 with MYCN amplification (any age)
- •Stage 4 without MYCN amplification (>1.5 years of age)
- •Stage 3 with MYCN amplification (unresectable; any age)
- •Stage 4S with MYCN amplification (any age)
- •Patients fulfill one of the following criteria:
- •Have evidence of soft tissue disease OR
- •If they only have osteomedullary disease at protocol enrollment, they should have:
- •Had previously received Hu3F8+GMCSF therapy AND have had less than a complete response to it OR
- •Had progressed progressive disease after their most recent anti-neuroblastoma therapeutic regimen
- •Patients must have evaluable (microscopic marrow metastasis, elevated tumor markers, positive MIBG or PET scans) or measurable (CT, MRI) disease documented after completion of prior systemic therapy.
- •Prior treatment with murine and hu3F8 is allowed.
- •Prior treatment with irinotecan or temozolomide is permitted.
- •Patients with prior m3F8, hu3F8, ch14.18 or hu14.18 treatment must have a negative HAHA antibody titer. Human anti-mouse antibody positivity is allowed.
- •Signed informed consent indicating awareness of the investigational nature of this program.
排除标准
- •Patients with CR/VGPR disease
- •Existing severe major organ dysfunction, i.e., renal, cardiac, hepatic, neurologic, pulmonary, or gastrointestinal toxicity ≥ grade 3 except for hearing loss, alopecia, anorexia, nausea, and hypomagnesemia from TPN, which may be grade 3
- •ANC < 500/uL
- •Platelet count <30K/uL
- •History of allergy to mouse proteins
- •Active life-threatening infection
- •Inability to comply with protocol requirements
- •Women who are pregnant or breast-feeding
研究组 & 干预措施
Hu3F8, Irinotecan/Temozolomide and Sargramostim (HITS)
Each cycle consists of four doses of hu3F8, five doses each of irinotecan and temozolomide and five doses of GM-CSF.
干预措施: Hu3F8 (Biological)
Hu3F8, Irinotecan/Temozolomide and Sargramostim (HITS)
Each cycle consists of four doses of hu3F8, five doses each of irinotecan and temozolomide and five doses of GM-CSF.
干预措施: Irinotecan (Drug)
Hu3F8, Irinotecan/Temozolomide and Sargramostim (HITS)
Each cycle consists of four doses of hu3F8, five doses each of irinotecan and temozolomide and five doses of GM-CSF.
干预措施: temozolomide (Drug)
Hu3F8, Irinotecan/Temozolomide and Sargramostim (HITS)
Each cycle consists of four doses of hu3F8, five doses each of irinotecan and temozolomide and five doses of GM-CSF.
干预措施: GM-CSF (Drug)
结局指标
主要结局
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
时间窗: 2 years
The regimen will be considered safe if there are no toxicities requiring discontinuation of therapy in at least 9/10 patients during the first two cycles.
response rate (CR+PR)
时间窗: 2 years
Response assessment will be based on the best response over the course of four cycles. Disease response for NB will use the International NB Response Criteria. Patients who withdraw from the study prior to cycle 4 with \< partial response will also not be considered evaluable for response and will be replaced.
次要结局
未报告次要终点