A Phase 2a Study of Ultratrace™ Iobenguane I 131 in Patients With Relapsed/Refractory High-Risk Neuroblastoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 15
- 试验地点
- 8
- 主要终点
- Maximum Tolerated Dose
研究概览
简要总结
RATIONALE: Radioactive drugs, such as iodine I 131 metaiodobenzylguanidine (MIBG), may carry radiation directly to tumor cells and not harm normal cells. A bone marrow or peripheral stem cell transplant using stem cells from the patient may be able to replace blood-forming cells that were destroyed by I 131 MIBG.
PURPOSE: This phase II trial is studying the side effects and best dose of iodine I 131 MIBG followed by a stem cell transplant in treating young patients with relapsed or refractory high-risk neuroblastoma.
详细描述
OBJECTIVES:
Primary
- To establish the maximum tolerated dose of iodine I 131 metaiodobenzylguanidine (^131I-MIBG) in patients with relapsed/refractory high-risk neuroblastoma.
Secondary
- To describe toxicity following treatment with ^131I-MIBG in patients with relapsed/refractory high-risk neuroblastoma.
- To estimate radiation absorbed doses to measurable lesions and to a standard set of normal organs following a 0.1 mCi/kg [3.7 MBq/kg] (minimum dose of 1.0 mCi [37 MBq] but not to exceed 5.0 mCi [185 MBq]) intravenous administration of ^131I-MIBG in patients with relapsed/refractory high-risk neuroblastoma.
- To describe, within the confines of a phase IIa trial, objective tumor response following treatment with ^131I-MIBG in patients with relapsed/refractory high-risk neuroblastoma.
- To explore dose-response following treatment with ^131I-MIBG in patients with relapsed/refractory high-risk neuroblastoma.
- To explore quality of life assessment following treatment with ^131I-MIBG in patients with relapsed/refractory high-risk neuroblastoma.
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
- •Patients must be at least one year and no more than 30 years of age when registered on this study.
- •Patients must have high risk neuroblastoma and either have tumor left after treatment started at diagnosis or have had the tumor grow back (relapsed) after getting some treatment
- •Patients must an MIBG scan done and it must be positive for neuroblastoma.
- •Patients must have a PBSC or bone marrow stem cell product available that meets study criteria. If they don't already have stem cells frozen away then they must be able to have a stem cell pheresis done to collect the necessary amount of stem cells for study entry and these stem cells must meet study criteria.
- •Patients must have adequate heart, lung, liver, kidney and bone marrow function.
排除标准
- •They have had a stem cell transplant using another person as the stem cell donor. (You can still be in the study if a previous transplant used your own stem cells)
- •They have other medical problems that could get much worse if they had this treatment.
- •They are on dialysis for badly working kidneys or have other kidney problems.
- •They are pregnant or breast feeding.
- •They have tumor in the brain or spinal cord that is seen on a CT or MRI scan one month before starting treatment
- •They had total body radiation or radiation to the entire belly.
- •They have a known allergy to MIBG, iodine or SSKI.
- •They can't cooperate with the special precautions that are needed during UltratraceTM MIBG treatment or with other safety monitoring requirements of the study..
研究组 & 干预措施
Ultratrace™ Iobenguane I 131
Eligible patients received a diagnostic imaging dose of Ultratrace™ Iobenguane I 131 (1-5 mCi) within 7 days of study enrollment, followed by three dosimetry scans over 3-6 days. If the imaging dose demonstrated normal biodistribution and tumor uptake, then the patient received a therapeutic dose within 7-28 days of the diagnostic imaging dose, followed by a single imaging scan on Day 7 post therapy. As per protocol, therapeutic dosing was to begin at 12.0 mCi/kg and escalate to 15.0, 18.0, and 21.0 mCi/kg until the MTD was established or the 21.0 mCi/kg dose level was reached. Actual doses administered ranged from 8.8 to 18.6 mCi/kg. Based on actual doses administered, patients were grouped into 3 mean dose groups: 11.2, 15.5, and 18.2 mCi/kg.
The dosimetry dose was administered over a period of 1-3 minutes by injection; the therapeutic dose was diluted in up to 25 mL normal saline and infused intravenously over 30 to 60 minutes.
干预措施: UltratraceTM Iobenguane I 131 Imaging (Drug)
Ultratrace™ Iobenguane I 131
Eligible patients received a diagnostic imaging dose of Ultratrace™ Iobenguane I 131 (1-5 mCi) within 7 days of study enrollment, followed by three dosimetry scans over 3-6 days. If the imaging dose demonstrated normal biodistribution and tumor uptake, then the patient received a therapeutic dose within 7-28 days of the diagnostic imaging dose, followed by a single imaging scan on Day 7 post therapy. As per protocol, therapeutic dosing was to begin at 12.0 mCi/kg and escalate to 15.0, 18.0, and 21.0 mCi/kg until the MTD was established or the 21.0 mCi/kg dose level was reached. Actual doses administered ranged from 8.8 to 18.6 mCi/kg. Based on actual doses administered, patients were grouped into 3 mean dose groups: 11.2, 15.5, and 18.2 mCi/kg.
The dosimetry dose was administered over a period of 1-3 minutes by injection; the therapeutic dose was diluted in up to 25 mL normal saline and infused intravenously over 30 to 60 minutes.
干预措施: UltratraceTM Iobenguane I 131 Therapy (Drug)
结局指标
主要结局
Maximum Tolerated Dose
时间窗: Day 60 +/-10 or Engraftment, whichever comes first
The maximum tolerated dose (MTD) was defined as the dose immediately below the level at which dose escalation would be stopped due to dose limiting toxicities (DLTs). Once the MTD was reached, an additional 3 patients were to be treated at that dose level, for a total of 6 patients at that planned dose level. DLTs were defined as any of the events that are possibly, probably or definitely attributable to UltratraceTM iobenguane I 131. The MTD was supposed to be the highest dose tested at which fewer than 1/3 of pts experience a DLT when 6 patients have been treated at the MTD but the dosimetry results indicated that the maximal dosage allowed to normal organs would be exceeded if the highest planned dose (21.0 mCi/kg) was administered, so the highest dose administered in the study was 18.6 mCi/kg .
次要结局
- Dosimetric Estimation of Radiation Absorbed Doses to Measurable Lesions(Day 5 post Dosimetric Dose)
- Quality of Life(Day 60 +/- 10 days post Therapeutic Dose)
- Overall Objective Tumor Response Post Therapeutic Treatment(Day 60 +/- 10 days post Therapeutic Dose)
- Dose Limiting Toxicities(From the time of signed informed consent until Day 60 or until the end of therapy evaluation is completed (whichever comes first).)
- Tumor Response in CT/MRI Lesions Post Therapeutic Treatment(Day 60 +/- 10 days post Therapeutic Dose)