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.
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