A PHASE II TRIAL OF RITUXAN IN MULTIPLE SCLEROSIS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。Rituxan （Genetech）是一种针对b细胞特异性抗原CD20的人源化单克隆抗体。它已经被用于治疗非霍奇金淋巴瘤好几年了。有几百人使用这种药物的经验，但没有在多发性硬化症患者。以375mg/m2为单位，分4次静脉给药，间隔1周。这种剂量可以在治疗后的6个月内完全消除循环中的B细胞。有相当大的数据,B细胞和/或抗体可能参与的jpathogenesis女士然而,B细胞是否真正发挥作用,需要评估是否eliminiation好处因此女士,作为第一步,我们提出一个30个病人,II期临床试验的安全性和有效性在30患者积极治疗,复发患者继续服用女士的标准剂量β干扰素在审判。参加试验的受试者必须在治疗前的三次脑部核磁共振成像中有两次钆增强病变的证据，并且在入组前的18个月内至少有一次临床复发，尽管正在接受干扰素治疗。终点将是安全性，即药物的毒性和MS恶化的可能性，以及基于MRI活性替代测量的有效性。主要疗效终点将是治疗后进行的每月3次的脑部核磁共振成像与治疗前进行的每月3次核磁共振成像相比，钆增强病变的体积减少。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Rituxan (Genetech) is a humanized monoclonal antibody directed against the B-cell specific antigen, CD20. It has been used for several years in the therapy of non-Hodgkin's lymphoma. There is experience using this agent in several hundred human subjects, but not in MS patients. The agent will be administered intravenously in 4 doses, one week apart of 375mg/m2. This dose eliminates circulating B cells completely for up to 6 months following therapy. There is considerable data that B cells and/or antibody may be involved in the jpathogenesis of MS. However, to determine whether B cells truly play a role will require an assessment of whether their eliminiation benefits the course of MS. Therefore, as a first step we propose a 30 patient, Phase II trial of the safety and efficacy of Rituxan in 30 patients with active, relapsing MS. Patients will continue taking the standard dose of beta-interferon while in the trial. Subjects enrolled in the trial must have evidence of two gadolinium0enhacing lesions on any of three pre-treatment brain MRIs, and will have had at least one clinical relapse in the 18months prior to enrollment, despite being on beta-interferon therapy. The endpoints will be safety, in terms of toxicity of the agent and the possibility of worsening of MS, and efficacy based on the surrogate measure of MRI activity. The primary efficacy endpoint will be reduction in volume of gadolinium-enhancing lesions on the 3-once-monthly brain MRIs performed post-treatment in comparison to the three once-monthly MRIs performed pre-treatment.