VELCADE IN PATIENTS WITH RELAPSED OR REFRACTORY WALDENSTROM'S MACROGLOBULINEMIA

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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. In the relapsed and refractory setting, response rates of approximately 30% with durations of response of one year have been observed with currently recommended therapeutics in Waldenstrom's macroglobulinemia (WM). Moreover, the use (or re-use) of alkylator agents such as Chlorambucil as well as nucleoside analogues raise concerns over potential inflicting stem cell injury, and therefore compromising future autologous transplant efforts. Therefore, the exploration of novel therapeutics in this setting appears warranted. Initial experience with VELCADE suggests that collection of stem cells post-therapy is feasible, though more studies are needed for clarification. In addition, the reported response rates of VELCADE in patients with multiple myeloma, a closely related disease to WM is approximately 30% therefore on par with that observed in the use of therapeutics in the relapsed/refractory setting of WM. While the success of VELCADE in multiple myeloma (MM) does not per se predict for an equivalent response in WM, similar efficacy in the pre-clinical setting has been observed in laboratory studies for both diseases. The schema to be utilized in this study was adopted from the recently completed Phase II study of VELCADE in a comparable group of patients with MM, wherein both efficacy and tolerability were established. This is an Phase II, multicenter study designed to evaluate the efficacy and safety of VELCADE at a dose of 1.3 mg/m2/dose, administered in up to eight treatment cycles to patients with WM who have relapsed or refractory disease following frontline therapy. A treatment cycle is comprised of four injections of VELCADE (on Days 1, 4, 8, and 11) followed by a 10-day rest period. Procedures to be performed during treatment include monitoring for adverse events, including a directed questionnaire for neurologic toxicities, vital signs before and following each dose, review of concomitant medications and other support therapies, including growth factors and transfusions, disease assessments, and clinical laboratory tests.