Phase I/II study of an anti-CD30 monoclonal antibody (MDX-060) in Hodgkin's lymphoma and anaplastic large-cell lymphoma
Phase I/II study of an anti-CD30 monoclonal antibody (MDX-060) in Hodgkin's lymphoma and anaplastic large-cell lymphoma
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DOI：
10.1200/jco.2006.07.8972
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发表时间：
2007-07-01
影响因子：
45.3
通讯作者：
Borchmann, Peter
中科院分区：
文献类型：
--
作者：
Ansell, Stephen M.;Horwitz, Steven M.;Borchmann, Peter
目的MDX-060是一种人源抗CD 30免疫球蛋白（IG）G1 κ单克隆抗体，在临床前模型中可抑制表达CD 30的肿瘤细胞的生长。为了确定复发或难治性CD 30+淋巴瘤患者的安全性、最大耐受剂量（MTD）和MDX-060的疗效，进行了连续的I期和II期研究。Patients and MethodsIn the phase I portion，MDX-060以0.1、1、5或10 mg/kg的剂量每周静脉内给药4周至3至6名患者的队列。21例患者-16例霍奇金淋巴瘤（HL），3例间变性大细胞淋巴瘤（ALCL），2例CD 30 + T细胞淋巴瘤-入组。由于缺乏确定的MTD或剂量-反应相关性，对II期部分进行了修订，以纳入几个剂量水平。在第二阶段的部分，另外51例患者，47与HL和4与ALCL，治疗剂量为1，5，10和15 mg/kg.ResultsMDX-060耐受性良好，和MTD尚未确定。只有7%的患者发生了3级或4级治疗相关不良事件。在接受治疗的72例患者中，6例观察到临床反应。25例患者病情稳定，其中5人仍然没有进展1年后treatment.ConclusionMDX-060耐受性良好，剂量高达15 mg/kg。MDX-060作为单一药物具有有限的活性，但观察到的最小毒性和具有稳定疾病的显著比例的患者表明，有必要进一步研究MDX-060与其他疗法的组合。
PurposeMDX-060 is a human anti-CD30 immunoglobulin (Ig) G1 kappa monoclonal antibody that inhibits growth of CD30-expressing tumor cells in preclinical models. To determine the safety, maximum-tolerated dose (MTD), and efficacy of MDX-060 in patients with relapsed or refractory CD30+ lymphomas, sequential phase I and II studies were performed.Patients and MethodsIn the phase I portion, MDX-060 was administered intravenously at doses of 0.1, 1, 5, or 10 mg/kg weekly for 4 weeks to cohorts of three to six patients. Twenty-one patients-16 with Hodgkin's lymphoma (HL), three with anaplastic large-cell lymphoma (ALCL), and two with CD30+ T-cell lymphoma-were enrolled. Because of the lack of a defined MTD or dose-response correlation, the phase II portion was amended to include several dose levels. In the phase II portion, an additional 51 patients, 47 with HL and four with ALCL, were treated at doses of 1, 5, 10, and 15 mg/kg.ResultsMDX-060 was well tolerated, and an MTD has not been identified. Only 7% of patients experienced grade 3 or 4 treatment-related adverse events. Among the 72 patients treated, clinical responses were observed in six. Twenty-five patients had stable disease, including five who remained free from progression 1 year after treatment.ConclusionMDX-060 was well tolerated at doses up to 15 mg/kg. MDX-060 has limited activity as a single agent, but the minimal toxicity observed and the significant proportion of patients with stable disease suggests that further study of MDX-060 in combination with other therapies is warranted.