Phase III Placebo-Controlled Trial of Denileukin Diftitox for Patients With Cutaneous T-Cell Lymphoma
Phase III Placebo-Controlled Trial of Denileukin Diftitox for Patients With Cutaneous T-Cell Lymphoma
复制标题
DOI：
10.1200/jco.2009.26.2386
复制
发表时间：
2010-04-10
影响因子：
45.3
通讯作者：
Negro-Vilar, Andres
中科院分区：
文献类型：
--
作者：
Prince, H. Miles;Duvic, Madeleine;Negro-Vilar, Andres
目的：本研究为III期、安慰剂对照、随机试验，旨在研究两种剂量的地尼白介素Diftitox的有效性和安全性（DD; DAB（389）-白细胞介素-2 [IL-2]），一种靶向表达IL-2受体的恶性T淋巴细胞的重组融合蛋白，用于IA至III期、CD 25检测阳性的皮肤T细胞淋巴瘤（CTCL）患者，包括蕈样肉芽肿和塞扎里综合征，他们接受了多达三种先前的治疗。主要终点是总反应率（ORR）。患者和方法将活检证实的CD 25检测阳性CTCL患者随机分配至DD 9 μ g/kg/d组（45例）、DD 18 μ g/kg/d组（55例）或安慰剂组（44例），每3周连续给药5天，最多8个周期。患者的药物疗效，临床效益和安全性的DD。结果ORR为44%，所有参与者治疗DD在= 100; 10%完全反应[CR]和34%部分反应[PR]）相比，15.9%的安慰剂治疗的患者12%CR和13.6%PR）。18 μ g/kg/d组的ORR高于9 μ g/kg/d组（分别为49.1%和37.8%），两种剂量均显著上级安慰剂。两种DD剂量组的无进展生存期（PFS）均显著长于安慰剂组（中位数，124天; P
Purpose This phase III, placebo-controlled, randomized trial was designed to investigate efficacy and safety of two doses of denileukin diftitox (DD; DAB(389)-interleukin-2 [IL-2]), a recombinant fusion protein targeting IL-2 receptor expressing malignant T lymphocytes, in patients with stage IA to III, CD25 assay positive cutaneous T-cell lymphoma (CTCL), including the mycosis fungoides and Sezary syndrome forms of the disease, who had received up to three prior therapies. The primary end point was overall response rate (ORR).Patients and Methods Patients IN = 144) with biopsy-confirmed, CD25 assay positive CTCL were randomly assigned to DD 9 mu g/kg/d In = 45), DD 18 mu g/kg/d In = 55), or placebo infusions In = 44), administered for 5 consecutive days every 3 weeks for up to eight cycles. Patients were monitored for drug efficacy, clinical benefit, and safety of DD.Results ORR was 44% for all participants treated with DD In = 100; 10% complete response [CR] and 34% partial response [PR]) compared with 15.9% for placebo-treated patients 12% CR and 13.6% PR). ORR was higher in the 18 mu g/kg/d group versus the 9 mu g/kg/d group (49.1% v 37.8%, respectively), and both doses were significantly superior to placebo. Progression-free survival (PFS) was significantly longer (median, > 2 years) for both DD doses compared with placebo (median, 124 days; P