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

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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.