NANT 2002-01 PHASE 1 STUDY OF HIGH DOSE PYRASOLACRIDINE (PZA)(NSC 366140) SUPPOR

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。复发的高危神经母细胞瘤患者预后不佳，目前尚无有效的治疗方法。这是一项静脉注射药物焦唑吖啶（PZA）的I期研究。PZA的工作原理是将自己插入DNA分子之间，这样DNA就无法复制，细胞也无法分裂。PZA已经在儿童和成人I期研究中进行了有限活性的研究。然而，在通常对化疗非常耐药的神经母细胞瘤细胞系中，有希望的临床前数据使这组患者对PZA保持了兴趣。有数据表明，PZA在以前的研究中可能没有起作用的原因是由于长期接触该药物的时间有限。因此，本研究使用至少6小时的长时间输注。也有理由相信，之前的剂量可能不够高，不足以起作用。剂量限制性毒性包括低血球计数和神经毒性。在本研究中，随着输注时间的延长，未观察到神经毒性。低计数可以通过干细胞抢救来治疗。干细胞拯救是当你注入从外周血中收集的干细胞并在化疗前储存。这已经被用作高风险神经母细胞瘤患者标准一线治疗的一部分。为了有资格参加这项研究，患者必须储存自己的一些干细胞。病人很可能已经储存了一些他们之前接受过治疗的干细胞。只有当患者出现长期的低血球计数，或者患者出现危及生命的毒性时，本研究才需要它们。这项研究的所有患者将只接受一个疗程的PZA治疗。

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. High-risk neuroblastoma patients who relapse have a dismal prognosis and there is no known effective therapy. This is a phase I study of the intravenous agent pyrozolocridine (PZA). PZA works by inserting itself in between DNA molecules such that DNA cannot duplicate and cells cannot divide. PZA has already been studied in pediatric and adult phase I studies with limited activity. However, promising pre-clinical data in neuroblastoma cell lines that are normally very resistant to chemotherapy has maintained interest in PZA for this group of patients. There is data that suggest that the reason PZA might not have worked in previous studies is due to limited exposure to the drug over time. Therefore, this study uses a prolonged infusion of at least 6 hours. There is also reason to believe that previous doses might not have been high enough to work. Dose-limiting toxicities have included low blood counts and neurotoxicity. The neurotoxicity is not observed with the longer infusion times used in this study. The low counts can be treated by using stem cell rescue. Stem cell rescue is when you infuse stem cells that were collected from the peripheral blood and stored prior to chemotherapy. This is already used as a part of standard front-line therapy for high-risk neuroblastoma patients. To be eligible for this study, patients must have some of their own stem cells stored. It is likely that patients will already have some stem cells in storage from their previous therapies. They will only be needed for this study if patients experienced prolonged low blood counts, or if the patient experiences life-threatening toxicity. All patients on this study will receive only one course of treatment with PZA.