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

目前的序贯试验设计利用机会窗口来评估PS-341单独治疗侵袭性大细胞淋巴瘤的效果。然而，由于复发性DLBCL可能通过EPOCH单独化疗（20%）或干细胞移植（25%）治愈，因此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在复发性和未治疗的DLBCL中得到验证，并且是一种潜在的可治愈方案。因此，如果PS-341被证明是有活性的，它可能与EPOCH联合用于预后不良的NF-κ B表达DLBCL的初始治疗。 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（DLBCL）以及ABC和GCB分子亚型中的缓解。1.1.2评估PS-341和EPOCH在DLBCL中的毒性和安全耐受剂量。1.1.3获取DLBCL中PS-341和EPOCH响应的导频信息。 次要1.1.4使用微阵列和IHC评估PS-341对DLBCL肿瘤活检的生物学效应，包括bcl-2和NF-κ B。 1.1.5评估对PS-341和EPOCH应答的耐药性标志物（bcl-2、MIB-1、p53）。

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-kB-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-kB. 1.1.5 Assess markers of drug resistance (bcl-2, MIB-1, p53) on response to PS-341 and EPOCH.