VELCADE IN PATIENTS WITH RELAPSED OR REFRACTORY WALDENSTROM'S MACROGLOBULINEMIA

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。在复发和难治性情况下，目前推荐的治疗方法在Waldenstrom巨球蛋白血症（WM）中观察到的缓解率约为30%，持续时间为一年。此外，烷基化剂的使用（或重复使用），如氯苯以及核苷类似物，引起了对潜在的干细胞损伤的担忧，因此影响了未来的自体移植工作。因此，在这种情况下，探索新的治疗方法似乎是必要的。VELCADE的初步经验表明，治疗后收集干细胞是可行的，尽管需要更多的研究来澄清。此外，据报道，VELCADE在多发性骨髓瘤（一种与WM密切相关的疾病）患者中的反应率约为30%，因此与在复发/难治性WM中使用治疗药物所观察到的反应率相当。虽然VELCADE在多发性骨髓瘤（MM）中的成功本身并不能预测在WM中的同等疗效，但在两种疾病的实验室研究中，在临床前环境中观察到相似的疗效。本研究中使用的方案采用了最近完成的VELCADE在一组相似的MM患者中的II期研究，该研究建立了疗效和耐受性。这是一项II期多中心研究，旨在评估VELCADE在1.3 mg/m2/剂量下的疗效和安全性，在长达8个治疗周期中给予一线治疗后复发或难治性疾病的WM患者。治疗周期包括四次注射VELCADE（第1、4、8和11天），然后是10天的休息期。治疗期间应执行的程序包括监测不良事件，包括神经毒性的直接调查问卷、每次给药前后的生命体征、对伴随用药和其他支持疗法（包括生长因子和输血）的审查、疾病评估和临床实验室检查。

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.