COG ADVL0317: A PHASE I STUDY OF PS-341 (VELCADE, BORTEZOMIV) IN PED PATIENTS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。这项I期研究测试了一种名为PS-341(Velade或Bortezomib)的新药在难治性/复发性白血病患者中的安全性。(白血病是一种影响儿童血细胞的癌症，复发意味着疾病在治疗后复发，难治意味着这种疾病很难治疗。)使用PS-341进行的实验室实验表明，它通过阻止癌细胞的生长来杀死癌细胞。已经在成人和儿童实体瘤患者中发现了安全剂量的PS-341，但在白血病儿童中尚未发现安全剂量。这项研究的目的是测试PS-341的安全性，看看它们对儿童和儿童白血病有什么效果(好的和坏的)，并找到可以给白血病儿童服用而不会引起严重副作用的最高剂量。这项研究的其他目标是了解人体如何处理药物，并更好地了解癌细胞与健康细胞的不同之处。这项研究是这样设计的，孩子们被分成几组。第一组儿童将在开始剂量时给予PS-341。如果起始剂量的副作用不是太严重，下一组儿童将被给予更高剂量的PS-341。这将继续下去，直到找到不会导致不可接受的副作用的最大剂量。PS-341的剂量不会在每个儿童身上增加。每个疗程将持续21天。在每个疗程中，患者将在每个疗程的第1、4、8和11天给予PS-341。PS-341将通过静脉给药。治疗过程的样本概述如下：周一周二周三周四周五周六周日1周PS-341 PS-341周2 PS-341 PS-341周3休息期；本周不给予PS-341第18-22天评估：如果疾病没有恶化且副作用可耐受，则撤退本研究的儿童在治疗期间将接受标准体检，如体检、蛋白质水平测试以及肝肾功能检查。对于前三个疗程，在每个疗程结束时将进行骨髓抽吸，然后在每隔一个疗程结束时进行骨髓抽吸。除了这些标准测试外，患者还可以选择在第一个疗程的几天内采集血液样本，进行称为药代动力学的测试。药代动力学测试发现药物在体内细胞中的行为方式。患者还可以选择参加其他涉及他们的骨髓和血液样本的特殊研究。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This phase I study tests the safety of a new experimental drug called PS-341 (Velcade or Bortezomib) in refractory/recurrent leukemia patients. (Leukemia is a type of cancer that affects a child's blood cells, recurrent means the disease came back after being treated, and refractory means that the disease is hard to treat.) Laboratory experiments performed with PS-341 showed that it kills cancer cells by stopping their growth. A safe dose of PS-341 has already been found in adults and in children with solid tumors, but a safe dose has not been found in children with leukemia. The goals of this study are to test the safety of PS-341, to see what effects (good and bad) they have on children and children's leukemia, and to find the highest dose of PS-341 that can be given to children with leukemia without causing severe side effects. Other goals of this study are to learn how the body handles the drug, and to better understand how cancer cells are different from healthy cells. The study is designed such that the children are separated into groups. The first group of children will be given PS-341 at the starting dose. If the side effects at the starting dose are not too serious, the next group of children will be given a higher dose of PS-341. This will continue until the maximum dose is found that does not result in unacceptable side effects. The dose of PS-341 given will not be increased in each individual child. Each course of therapy will last 21 days. During each course, the patient will be given PS-341 on days 1, 4, 8 and 11 of each course. PS-341 will be given through a vein. A sample overview of a treatment course is below: Monday Tuesday Wednesday Thursday Friday Saturday Sunday Week 1 PS-341 PS-341 Week 2 PS-341 PS-341 Week 3 Rest period; no PS-341 is given this week Day 18-22 Evaluation: retreat if disease is not worse and side effects are tolerable Children on this study will be given standard medical exams during therapy, such as physical exams, protein level tests and tests to examine liver and kidney function. A bone marrow aspirate will be done at the end of every course for the first three courses, and then at the end of every other course. In addition to these standard tests, patients will be the given the option to have blood samples taken on a few days during the first course of therapy for tests called pharmacokinetics. Pharmacokinetic tests find out how the drug is behaving in cells in the body. Patients will also be given the option to participate in other special research studies involving their bone marrow and blood samples.