ADVL0319 PHASE I STUDY OF CC-5013 (LENALIDOMIDE) IN PEDIATRIC PATIENTS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。这项I期研究测试了一种名为CC-5013或来那度胺的新型实验性药物在实体瘤患者和骨髓增生异常综合征（MDS）患者中的安全性。CC-5013通过阻断某些细胞过程来阻止癌细胞的生长，从而导致细胞死亡。在成人中寻找安全剂量的CC-5013的研究正在进行I期试验，但还没有在儿童中进行CC-5013的试验。这项研究的目的是测试CC-5013的安全性，看看它对儿童和儿童癌症有什么影响（好的和坏的），并找到可以给患有实体瘤的儿童服用的最高剂量CC-5013，而不会造成严重的副作用。这项研究的其他目标是了解人体如何处理药物，并更好地了解肿瘤细胞与健康细胞不同的功能。CC-5013在实体瘤和MDS患者中的抗肿瘤作用也将被进一步研究。因为这个I期试验的主要目的是找到可以安全地给予患有实体瘤的儿童CC-5013的最大剂量，一些患者接受的剂量可能太小而对他们的癌症没有任何影响，或者可能太高而导致不良副作用。目前尚不清楚这种药物在任何剂量下对治疗癌症是否有效。患有实体瘤的儿童将被分成几组。第一组儿童将以起始剂量给予CC-5013。如果开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CC-5013。这一过程将持续到发现最大剂量不会产生不可接受的副作用为止。CC-5013的剂量不会在每个儿童中增加。患有MDS的儿童将不参与方案的剂量递增部分。相反，所有MDS患者将接受相同剂量的CC-5013治疗。CC-5013将用于MDS患者的剂量大致相当于已被证明对成年MDS患者具有临床效果的剂量。每疗程28天。在每个疗程中，患者将通过吞咽胶囊或食用洒在苹果酱上的CC-5013胶囊的内容物来给予CC-5013。CC-5013将在21天内每天给儿童服用，在下一次课程开始前有7天的休息时间。在这项研究中，只要患者的癌症没有恶化，只要没有不良副作用发生，就可以给予CC-5013，最多12个疗程，参加这项研究的儿童在治疗期间将接受标准的医学检查，如体检、血液检查、扫描或其他检查，以评估他们的肿瘤。除了标准测试之外，患者还可以选择抽取血液样本进行药代动力学测试，以了解药物在体内细胞中的表现，并进行测试以了解CC-5013对免疫功能的影响。

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 CC-5013, or lenalidomide in solid tumor patients and in patients with myelodysplastic syndrome (MDS). CC-5013 works to stop cancer cells from growing by blocking certain cell processes, causing the cell to die. Studies to find a safe dose of CC-5013 in adults are ongoing in Phase I trials like this one, but there have been no trials of CC-5013 in children yet. The goals of this study are to test the safety of CC-5013, to see what effects (good and bad) it has on children and children¿¿s cancer, and to find the highest dose of CC-5013 that can be given to children with solid tumors without causing severe side effects. Other goals of this study are to learn how the body handles the drug, and to better understand the functions in tumor cells that differ from healthy cells. The anti tumor effect of CC-5013 in solid tumor and MDS patients will also be studied. Because the main purpose of this phase I trial is to find the maximum dose of CC-5013 that can be safely given to children with solid tumors, the dose that some patients receive may be too small to have any effect on their cancer, or it may be too high and cause bad side effects. It is not known if this drug, at any dose, will be effective in treating cancer. Children with solid tumors will be separated into groups. The first group of children will be given CC-5013 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 CC-5013. This will continue until the maximum dose is found that does not result in unacceptable side effects. The dose of CC-5013 given will not be increased in each individual child. Children with MDS will not participate in the dose escalation portion of the protocol. Instead all patients with MDS will be treated with the same dose of CC-5013. The dose of CC-5013 that will be administered to patients with MDS is approximately equivalent to the dose that has been demonstrated to have clinical effect in adult patients with MDS. Each course of therapy will last for 28 days. During each course, the patient will be given CC-5013 by swallowing capsules, or by eating the contents of CC-5013 capsules sprinkled onto applesauce. CC-5013 will be given to children every day for 21 days, with a period of 7 days to rest before the next course begins. Patients on this study can be given CC-5013 as long as their cancer is not getting worse, and as long as no bad side effects happen, for up to 12 courses Children on this study will be given standard medical exams during therapy, such as physical exams, blood tests, and scans or other tests to evaluate their tumor. In addition to standard tests, patients will be the given the option to have blood samples taken for tests called pharmacokinetics to find out how the drug is behaving in cells the body, and for tests to learn what CC-5013 does to immune functions.