Phase I study of bortezomib and DA-EPOCH-R with microarray in DLBCL

目前的序贯试验设计利用了一个机会窗口来单独评估PS-341在侵袭性大细胞淋巴瘤中的作用。然而，由于复发的DLBCL有可能仅用Epoch化疗(20%)或干细胞移植(25%)治愈，因此没有进入CR的PS-341患者将接受PS-341和Epoch化疗。之所以选择Epoch化疗，是因为它的疗效在复发和未治疗的DLBCL中都得到了验证，是一种潜在的治愈方案。因此，如果PS-341被证明是活性的，它可能与EPOCH联合用于预后不良的DLBCL的初步治疗。1.1.研究目的：评估PS-341在弥漫性大B细胞淋巴瘤(DLBCL)以及ABC和GCB分子亚型中的反应。1.1.2评估PS-341和EPOCH对DLBCL的毒性和安全耐受量。1.1.3获取DLBCL的PS-341和EPOCH响应的引航员信息。使用微阵列和免疫组化技术评估PS-341对DLBCL肿瘤活检组织的生物学效应，包括bcl-2和NF-61547；B.1.1.5评估耐药标志物(bcl2、mib-1、p53)对PS-341和EPOCH的反应。

The present sequential trial design takes advantage of a window of opportunity to assess PS-341 alone in aggressive large cell lymphomas. However, because recurrent DLBCL is potentially curable with EPOCH chemotherapy alone ( 20%) or stem cell transplant ( 25%), patients who do not enter CR with PS-341 will receive PS-341 and EPOCH chemotherapy. EPOCH chemotherapy was selected because its efficacy has been validated in both recurrent and untreated DLBCL and is a potentially curable regimen. Hence, if PS-341 is shown to be active, it could potentially be combined with EPOCH for the initial treatment of poor prognosis NF-B-expressing DLBCL. 1.1. Study Objectives  Primary 1.1.1 Assess response of PS-341 in diffuse large B-cell lymphoma (DLBCL) and within the ABC and GCB molecular subtypes. 1.1.2 Assess toxicity and safe tolerated dose of PS-341 and EPOCH in DLBCL. 1.1.3 Obtain pilot information on response of PS-341 and EPOCH in DLBCL.  Secondary 1.1.4 Assess biological effect of PS-341 on DLBCL tumor biopsies using microarray and IHC, including bcl-2 and NF-B. 1.1.5 Assess markers of drug resistance (bcl-2, MIB-1, p53) on response to PS-341 and EPOCH.