CLINICAL TRIAL: PHASE 1 STUDY OF UCN-01 WITH PERIFOSINE IN PATIENTS WITH ACUTE L

临床试验：UCN-01 联合哌利福辛治疗急性 L 患者的 1 期研究

• 批准号: 7951153
• 负责人: IVANA GOJO
• 金额: $ 0.79万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7951153
• 关键词: Acids; Acute; Acute leukemia; Adverse effects; Affect; Algorithms; Antiemetics; Binding; Carboplatin; Clinical Research; Computer Retrieval of Information on Scientific Projects Database; Dose; Dose-Limiting; Funding; Glycoproteins; Grant; Hour; Hyperglycemia; Infusion procedures; Institution; Investigation; Maintenance; Marrow; Maryland; Maximum Tolerated Dose; Nausea; Patients; Perifosine; Pharmaceutical Preparations; Phase; Phase I Clinical Trials; Phosphorylation; Prophylactic treatment; Protocols documentation; Refractory; Relapse; Research; Research Personnel; Resources; Schedule; Source; Supportive care; Toxic effect; United States National Institutes of Health; Universities; Upper arm; experience; gastrointestinal; neoplastic cell

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 is a two arm, dose escalating Phase 1 study to determine the effects of UCN-01 and perifosine in combination in relapsed and refractory acute leukemias. UCN-01 will be dose escalated to a maximum tolerated dose/recommended phase 2 dose in the presence of the recommended phase 2 dose of perifosine. The sequence of administration of the two drugs will also be studied. The current proposed protocol will examine in a focused way whether in patients with circulating or marrow-accessible tumor cells each agent alone and in combination will affect akt phosphorylation status, the possible target of perifosine. Owing to the tight binding of UCN-01 to alpha1-acid glycoprotein, a Phase I escalation of UCN-01 is proposed initially in the presence of the recommended Phase 2 concentrations of perifosine to confirm the absence of unexpected toxicities of the combination. Neither agent was myelotoxic in initial Phase I studies conducted by a co-investigator of this proposed protocol. UCN-01 caused dose limiting hyperglycemia and nausea, while gastrointestinal side effects dominated in the case of perifosine. Note that the perifosine schedule proposed for use here utilizes a style of loading and maintenance perifosine doses that achieves similar perifosine concentrations with potentially continuous rather than interrupted dosing with manageable gastrointestinal toxicity, as compared to the interrupted schedule in the NCI phase 1 experience. Antiemetic prophylaxis will be routinely used prior to perifosine loading, and with UCN-01 as needed. In prior perifosine and UCN-01 phase 1 investigations, drug concentrations as single agents expected to modulate akt were achieved. UCN-01 will be administered as a three hour infusion, a schedule with which University of Maryland has experience and has already developed supportive care algorithms owing to a previous combined UCN-01 and carboplatin phase I experience.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 这是一项两臂，剂量升级的第一阶段研究，可确定UCN-01和perifosine在复发和难治性急性白血病中的组合中的影响。 UCN-01将在建议的2阶段2剂量的perifosine剂量的情况下将剂量升级为最大耐受剂量/推荐阶段2剂量。还将研究两种药物的给药顺序。当前提出的方案将以重点的方式检查，无论单独和组合循环或可掌握的肿瘤细胞患者是否会影响Akt磷酸化状态，这是perifosine的可能目标。由于UCN-01与α1-酸糖蛋白的紧密结合，最初提出了UCN-01的I期升级，最初是在建议的2期perifosine浓度的存在下确认没有意外的组合毒性的。该提议方案的共同研究器进行的初始I阶段研究中，这两种药物都不是骨髓毒性。 UCN-01引起剂量限制高血糖和恶心，而胃肠道副作用在perifosine的情况下占主导地位。请注意，与NCI第1阶段1经验中中断的时间表相比，此处提议使用的perifosine计划使用了一种载荷和维护perifosine剂量，具有具有可管理的胃肠道毒性的可能连续而不是中断的胃肠道毒性，而不是具有可管理的胃肠道毒性的可能连续而不是可管理的胃肠道毒性，而不是具有可管理的胃肠道毒性。抗过敏性预防将在perifosine载荷之前定期使用，并根据需要使用UCN-01。在先前的perifosine和UCN-01第1阶段研究中，预计将调节Akt的单一药物浓度。 UCN-01将作为三个小时的输液进行管理，马里兰州大学具有经验的时间表，并且由于以前的UCN-01和Carboplatin I期经验，已经开发了支持护理算法。