PHASE I TRIAL OF BORTEZOMIB (PS-341:NSC 681239) AND FLAVOPIRIDOL (NSC 649890)

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 本研究的主要目的是确定硼替佐米（PS341）和flavopiridol联合治疗复发性或难治性惰性B细胞肿瘤的II期推荐剂量。 其他目的是确定药物组合的毒性和最大耐受剂量，观察组合的疾病相关作用。观察该组合在来自骨髓瘤患者的正常和肿瘤外周骨髓细胞中对MCI-1、XIAP、磷酸化-JNK、NF-B和细胞凋亡的药效学作用，并描述当与硼替佐米（PS-341）组合施用时flavopiridol的药代动力学。 项目描述： 虽然有许多治疗淋巴瘤，骨髓瘤和相关癌症的方法，但大多数患者无法治愈。 这项研究的目的是改善淋巴瘤、骨髓瘤和相关癌症的治疗。 硼替佐米是一种相对较新的药物，已被批准用于治疗骨髓瘤，并在淋巴瘤和相关癌症中显示出有希望的活性。 实验室研究表明，将硼替佐米（也称为万珂或PS-341）与研究药物flavopiridol联合使用可能会实现这一目标。 这项研究是研究性的，因为这种药物尚未被食品和药物管理局批准用于这些类型的癌症。 硼替佐米被认为是研究性的，因为尽管它已被批准用于骨髓瘤，但尚未被批准用于淋巴瘤或其他相关癌症。 硼替佐米和flavopiridol有标准剂量，但没有一起给药的经验。本研究的具体目的是确定硼替佐米和flavopiridol组合的适当剂量。 为了确定合适的剂量，将用不同的药物剂量治疗不同的患者，并观察其效果，特别是与较高剂量相关的副作用。

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. The primary objective of this study is to identify recommended phase II doses for the combination bortezomib (PS341) and flavopiridol in the treatment of recurrent or refractory indolent B cell neoplasms. Additional objectives are to determine the toxicities and maximum tolerated dose of the drug combination, to observe disease-related effects of the combination. to observe pharmacodynamic effects of the combination in normal and neoplastic peripheral bone marrow cells from patients with myeloma on MCI-1, XIAP, phospho-JNK, NF-B and apoptosis and to describe pharmacokinetics of flavopiridol when administered in combination with bortezomib (PS-341). Project Description: Although there are many treatments for lymphomas, myeloma, and related cancers, most patients are not cured. The purpose of this research is to improve the treatment of lymphomas, myeloma, and related cancers. Bortezomib, a relatively new agent, is approved agent for the treatment of myeloma, and it has shown promising activity in lymphoma and related cancers. Laboratory studies suggest that combining Bortezomib (also known as Velcade or PS-341) with the investigational drug, flavopiridol, may accomplish this. This study is investigational because this drug has not yet been approved by the Food and Drug Administration for use with this these types of cancer. Bortezomib is considered investigational because, although it has been approved for use in myeloma, is has not yet been approved for use in lymphoma or other related cancers. There are standard doses for bortezomib and flavopiridol, but there is no experience with giving the drugs together. The specific purpose of this study is to identify appropriate doses for the combination of bortezomib and flavopiridol. In order to identify appropriate doses, different patients will be treated with different drug doses and observed for the effects, especially the side effects associated with higher doses.