BIOLOGIC MODIFIER THERAPIES IN AIDS MALIGNANCIES

该申请是一项为期五年的艾滋病恶性肿瘤联盟（AMC）资助的竞争性续期，该资助目前授予俄亥俄州立大学（OSU）的Michael a . Caligiuri医学博士。在该奖项的过去四年中，PI积极参与了AMC淋巴瘤工作组和AMC实验室工作组。PI成功竞争了两项AMC临床试验的相关科学奖项，并且PI目前主持了一项AMC临床方案，该方案在HIV非霍奇金淋巴瘤（NHL）中使用生物反应调节剂。PI目前正在为AMC开发另外两项临床研究：第一项是在HIV NHL首次诱导治疗后进行低剂量白细胞介素（IL） 2的随机试验。这项研究可能会与欧洲的工业和艾滋病恶性肿瘤合作进行。AMC审查了意向书，并向AMC提交了一份协议。PI提交的第二项研究是一项II期研究，评估抗cd20单克隆抗体对移植后淋巴细胞增生性疾病（PTLD）患者的抗肿瘤活性。PTLD现在将作为一种免疫缺陷淋巴瘤纳入AMC议程，这将是AMC中第一个这样的协议。意向书已获AMC批准，协议也已提交。尽管俄勒冈州立大学及其前附属机构罗斯威尔公园癌症研究所做出了这些智力贡献，但其收益却很差，在13个主要癌症中心中排名约为第8位。因此，为了解决这一弱点，PI现在与四个新站点建立了联系，每个站点都有大量的HIV-1+患者和艾滋病恶性肿瘤患者，每个站点都是AMC的新成员。私家侦探不再隶属于罗斯威尔公园。这四个新地点包括马里兰大学癌症中心、埃默里大学布雷迪纪念医院、纽约圣文森特综合癌症中心和澳大利亚三家医院组成的联盟，该联盟隶属于一个名为国家艾滋病流行病学和临床研究中心（NCHECR）的共同临床研究小组。NCHECR评估和治疗绝大多数的HIV-1和艾滋病恶性患者为所有澳大利亚。俄勒冈州立大学的每一个附属网站都有其独特的优势。一些中心拥有大量的内城人口，其中有大量的妇女和少数民族患者，而其他中心则拥有非常强大的I-III期合作小组试验历史或独特的实验室专业知识。总的来说，这组新的俄勒冈州立大学附属站点应该为AMC带来几个优势，最明显的是增加了HIV NHL和HIV卡波西肉瘤的AMC方案。已经制定了一项预算，为每个附属机构提供最低限度的支持，以获得机构审查委员会批准的方案，并开始筛选患者进行研究。然而，在每个站点最初积累了4名患者之后，每个站点的资金就与他们积累患者的能力挂钩了。总的来说，与我们之前的应用程序相比，该应用程序在AMC的智力贡献和患者累积方面提供了增强的力量。

This application is a five year competing renewal for the AIDS Malignancy Consortium (AMC) grant currently awarded to Michael A. Caligiuri, M.D. at The Ohio State University (OSU). During the past four years of this award, the PI was an active participant in the AMC Lymphoma Working Group and the AMC Laboratory Working Group. The PI successfully competed for correlative science awards for two AMC clinical trials, and the PI currently chairs one AMC clinical protocol that uses a biologic response modifier in HIV non Hodgkin's lymphoma (NHL). Two additional clinical studies are currently under development by the PI for the AMC: The first is a randomized trial of low dose interleukin (IL) 2 following first induction therapy in HIV NHL. This study will likely be performed in collaboration with industry and AIDS malignancy sites in Europe. The letter of intent (LOI) was reviewed by the AMC and a protocol has been submitted to the AMC. The second study submitted by the PI is a phase II study assessing the anti-tumor activity of anti-CD20 monoclonal antibody against patients with posttransplant lymphoproliferative disorder (PTLD). PTLD will now be incorporated into the AMC agenda as an immunodeficiency lymphoma, and this will be the first such protocol within the AMC. The LOI as been approved by the AMC and the protocol has been submitted. Despite these intellectual contributions, the accrual of OSU and its former affiliate, Roswell Park Cancer Institute, was poor, ranking approximately 8th among 13 primary AMC sites. Therefore, in order to address this weakness, the PI has now affiliated with four new sites, each with a high patient volume of HIV-1+ patients and patients with AIDS malignancies, and each a new member to the AMC. The PI is no longer affiliating with Roswell Park. These four new sites include the University of Maryland Cancer Center, The Brady Memorial Hospital of Emory University, Saint Vincent's Comprehensive Cancer Center in New York, and a consortium of three hospitals in Australia that function under a common clinical research group called the National Center for HIV Epidemiology and Clinical Research (NCHECR). The NCHECR evaluates and treats the vast majority of HIV-1 and AIDS malignancy patients for all of Australia. Each of the OSU- affiliated sites has unique strengths. Some centers have large inner city populations with high volumes of women and minority patients, while other centers have extremely strong histories of phase I-III cooperative group trials or unique laboratory expertise. Collectively, this new group of OSU-affiliated sites should bring several strengths to the AMC, most notably an increase in accrual to AMC protocols for HIV NHL and HIV Kaposi's sarcoma. A budget has been structured to provide a minimal baseline of support for each affiliated site to get protocols approved by Institutional Review Boards and to begin to screen patients for study. However, after an initial accrual of four patients per site, the funding of each site becomes tied to their ability to accrue patients. Collectively, this application provides enhanced strength in intellectual contributions and patient accrual for the AMC, compared to our previous application.