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

本序贯试验设计利用了一个机会窗口， 评估单独的PS-341在侵袭性大细胞淋巴瘤中的作用。然而，由于复发性DLBCL是 单独使用EPOCH化疗（#61504; 20%）或干细胞治疗可能治愈 移植（#61504; 25%），PS-341未进入CR的患者将接受 PS-341和EPOCH化疗。选择EPOCH化疗是因为其疗效已被证实。 在复发和未治疗的DLBCL中均得到验证，并且是一种潜在的可治愈方案。因此，我们认为， 如果PS-341被证明是活跃的，它可能会与EPOCH相结合，用于最初的 治疗预后不良的NF-#61547; B表达DLBCL。1.1.研究目的 主要1.1.1评估PS-341在弥漫性大B细胞淋巴瘤中的反应 （DLBCL）和在ABC和GCB分子亚型内。1.1.2毒性和安全性评估 DLBCL中PS-341和EPOCH的耐受剂量。1.1.3获取飞行员对下列问题的反应信息： DLBCL中的PS-341和EPOCH。次要1.1.4评估生物效应 使用微阵列和IHC的PS-341对DLBCL肿瘤活检的影响，包括bcl-2和 NF-#61547;B。1.1.5评估耐药性标志物（bcl-2、MIB-1、p53）， 对PS-341和EPOCH的响应。

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.