背景:原发性中枢神经系统淋巴瘤(PCNSL)是一种高度侵袭性非霍奇金淋巴瘤(NHL),在过去30年中在免疫功能正常的患者中发病率不断上升。虽然结果有所改善,与全身性NHL相比,PCNSL的预后仍然较差。关于最佳治疗方法的许多问题仍然没有答案。
方法:这是一个随机的,开放标签,两个平行臂的国际III期试验。我们将从德国合作PCNSL研究组和国际结外淋巴瘤研究组网络内的约35个中心招募250名新诊断的PCNSL患者。所有入选患者将接受由4个周期的利妥昔单抗375mg/m(2)/d(第0天和第5天)组成的诱导化疗,甲氨蝶呤3.5g/m(2)(d1),阿糖胞苷2×2g/m(2)/d(d2-3),和噻替帕30毫克/米(2)(d4)每21天。所有患者将在第二个周期后进行干细胞收获。经过4个周期的诱导化疗,达到部分或完全缓解的患者将被集中随机分为2种不同的巩固治疗:(A)利妥昔单抗375mg/m的常规剂量免疫化疗(2)(d0),地塞米松40mg/d(d1-3),依托泊苷100mg/m(2)/d(d1-3),异环磷酰胺1500mg/m(2)/d(d1-3)和卡铂300mg/m(2)(d1)(R-DeVIC)或(B)大剂量化疗BCNU(或白消安)和噻替帕后自体干细胞移植(HCT-ASCT)。目的是证明与R-DeVIC相比,HCT-ASCT在无进展生存期方面的优越性(PFS,主要终点)。次要终点包括总生存期(OS),治疗反应和治疗相关的发病率。治疗完成后的最小随访时间为24个月。
结论:在PCNSL中进行巩固治疗的理由是消除残留的淋巴瘤细胞并降低复发风险。这可以通过以常规剂量或以需要自体干细胞支持的高剂量施用穿过血脑屏障的药剂来实现。HCT-ASCT已被证明对新诊断的PCNSL患者是可行且高效的。然而,目前尚不清楚,在新诊断的PCNSL患者中,强化抗代谢物免疫化疗后,HCT-ASCT是否真的优于常规剂量化疗.为了回答这个问题,我们设计了这项研究者发起的随机III期试验.
背景:德国临床试验注册中心DRKS00005503于2014年4月22日注册,ClinicalTrials.govNCT02531841于2015年8月24日注册。
BACKGROUND: Primary central nervous system lymphoma (PCNSL) is a highly aggressive Non-Hodgkin lymphoma (NHL) with rising incidence over the past 30 years in immunocompetent patients. Although outcomes have improved, PCNSL is still associated with inferior prognosis compared to systemic NHL. Many questions regarding the optimal therapeutic approach remain unanswered.
METHODS: This is a randomized, open-label, international phase III
trial with two parallel arms. We will recruit 250 patients with newly diagnosed PCNSL from approximately 35 centers within the networks of the German Cooperative PCNSL
study group and the International Extranodal Lymphoma
Study Group. All enrolled patients will undergo induction chemotherapy consisting of 4 cycles of rituximab 375 mg/m(2)/d (days 0 & 5), methotrexate 3.5 g/m(2) (d1), cytarabine 2 × 2 g/m(2)/d (d2-3), and thiotepa 30 mg/m(2) (d4) every 21 days. All patients will undergo stem-cell harvest after the second cycle. After 4 cycles of induction chemotherapy, patients achieving partial or complete response will be centrally randomized to 2 different consolidation treatments: (A) conventional-dose immuno chemotherapy with rituximab 375 mg/m(2) (d0), dexamethasone 40 mg/d (d1-3), etoposide 100 mg/m(2)/d (d1-3), ifosfamide 1500 mg/m(2)/d (d1-3) and carboplatin 300 mg/m(2) (d1) (R-DeVIC) or (B) high-dose chemotherapy with BCNU (or busulfan) and thiotepa followed by autologous stem cell transplantation (HCT-ASCT). The objective is to demonstrate superiority of HCT-ASCT compared to R-DeVIC with respect to progression-free survival (PFS, primary endpoint). Secondary endpoints include overall survival (OS), treatment response and treatment-related morbidities. Minimal follow-up after treatment completion is 24 months.
CONCLUSIONS: The rationale for consolidation treatment in PCNSL is to eliminate residual lymphoma cells and to decrease the risk for relapse. This can be achieved by agents crossing the blood brain barrier either applied at conventional doses or at high doses requiring autologous stem cell support. HCT-ASCT has been shown to be feasible and highly effective in patients with newly-diagnosed PCNSL. However, it is unclear whether HCT-ASCT is really superior compared to conventional-dose chemotherapy after an intensified antimetabolites-based immunochemotherapy in patients with newly-diagnosed PCNSL. To answer this question, we designed this investigator initiated randomized phase III
trial.
BACKGROUND: German clinical trials registry DRKS00005503 registered 22 April 2014 and ClinicalTrials.gov NCT02531841 registered 24 August 2015.