A Comparative Pharmacokinetic and Safety Study of Chimeric Monoclonal Antibody ch14.18 With Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF), Interleukin-2 (IL-2) and Isotretinoin in High Risk Neuroblastoma Patients Following Myeloablative Therapy
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 28
- 试验地点
- 13
- 主要终点
- Peak Plasma Concentration (Cmax)
研究概览
简要总结
The purpose of this study is to compare the pharmacokinetics (blood levels) and safety of chimeric (ch) 14.18 manufactured by two independent drug makers (United Therapeutics [UTC] or the National Cancer Institute [NCI]).
详细描述
This is a multi-center, randomized, open-label, two-sequence, cross-over study for eligible subjects with high-risk neuroblastoma to assess the comparability of ch14.18 manufactured with UTC drug product and ch14.18 manufactured with NCI drug product. Subjects will be randomly allocated to receive ch14.18 manufactured by UTC or NCI during Courses 1 and 2 followed by ch14.18 manufactured by other manufacturer (UTC or NCI) during Courses 3, 4, and 5.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 8 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of high-risk neuroblastoma
- •8 years of age or younger at diagnosis of high-risk neuroblastoma
- •Patients must have completed therapy including intensive induction followed by autologous stem cell transplantation (ASCT) and radiotherapy
- •* Radiotherapy may be waived for patients who either have small adrenal masses which are completely resected up front, or who never have an identifiable primary tumor
- •Must meet the International Neuroblastoma Response Criteria (INRC) for CR, VGPR, or PR for primary site, soft tissue metastases, and bone metastases AND must also meet the protocol specified criteria for bone marrow response as follows:
- •* No more than 10% tumor (of total nucleated cellular content) seen on any specimen from a bilateral bone marrow aspirate/biopsy
- •Patient who have no tumor seen on the prior bone marrow, and then have ≤ 10% tumor on any of the bilateral marrow aspirate/biopsy specimens done at pre-ASCT and/or pre-enrollment evaluation will also be eligible
- •No more than 12 months from starting the first induction chemotherapy after diagnosis to the date of ASCT
- •* For patients who became high-risk neuroblastoma after initial non-high risk disease, the 12 months period should start from the date of induction therapy for high-risk neuroblastoma to the date of ASCT
- •No progressive disease at time of registration except for protocol-specified bone marrow response
- •Adequate hematological, renal, hepatic, pulmonary and cardiac function
- •CNS toxicity < Grade 2
排除标准
- •Prior anti-GD2 antibody therapy
- •Prior vaccine therapy for neuroblastoma
- •Concurrent anti-cancer or immunosuppressive therapy
研究组 & 干预措施
Sequence 1
UTC ch14.18 for two courses and NCI ch14.18 for three courses
干预措施: ch14.18 -NCI (Biological)
Sequence 1
UTC ch14.18 for two courses and NCI ch14.18 for three courses
干预措施: ch14.18-UTC (Biological)
Sequence 1
UTC ch14.18 for two courses and NCI ch14.18 for three courses
干预措施: Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) (Biological)
Sequence 1
UTC ch14.18 for two courses and NCI ch14.18 for three courses
干预措施: Aldesleukin (IL-2) (Biological)
Sequence 1
UTC ch14.18 for two courses and NCI ch14.18 for three courses
干预措施: Isotretinoin (Drug)
Sequence 2
NCI ch14.18 for two courses and UTC ch14.18 for three courses
干预措施: ch14.18 -NCI (Biological)
Sequence 2
NCI ch14.18 for two courses and UTC ch14.18 for three courses
干预措施: ch14.18-UTC (Biological)
Sequence 2
NCI ch14.18 for two courses and UTC ch14.18 for three courses
干预措施: Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) (Biological)
Sequence 2
NCI ch14.18 for two courses and UTC ch14.18 for three courses
干预措施: Aldesleukin (IL-2) (Biological)
Sequence 2
NCI ch14.18 for two courses and UTC ch14.18 for three courses
干预措施: Isotretinoin (Drug)
结局指标
主要结局
Peak Plasma Concentration (Cmax)
时间窗: PK samples obtained during Courses 1 and 3: Days 0, 3, 4, 5, 6, 7, 9, 10, 11, 14, 15, 16, 17; PK samples obtained during Courses 2 and 4: Days 0, 7, 10; End of Treatment
Twenty-two PK samples will be obtained at the following timepoints: Courses 1 and 3: Day: 0 Days: 3, 4, 5 and 6: post ch14.18 Days 7:10 to 14 hours post ch14.18 Days 9 to 11: Single sample Days 14 to 17: Single sample Courses 2 and 4: Day 0: Pre-IL-2 Day 7: Pre-ch14.18 Day 10 (Course 4 only): Post ch14.18 End of Treatment: Within 2 weeks post isotretinoin
Area Under the Plasma Concentration Curve (AUC)
时间窗: PK samples obtained during Courses 1 and 3: Days 0, 3, 4, 5, 6, 7, 9, 10, 11, 14, 15, 16, 17; PK samples obtained during Courses 2 and 4: Days 0, 7, 10; End of Treatment
Twenty-two PK samples will be obtained at the following timepoints: Courses 1 and 3: Day: 0 Days: 3, 4, 5 and 6: post ch14.18 Days 7:10 to 14 hours post ch14.18 Days 9 to 11: Single sample Days 14 to 17: Single sample Courses 2 and 4: Day 0: Pre-IL-2 Day 7: Pre-ch14.18 Day 10 (Course 4 only): Post ch14.18 End of Treatment: Within 2 weeks post isotretinoin
次要结局
未报告次要终点