BIOLOGIC MODIFIER THERAPIES IN AIDS MALIGNANCIES

这项申请是对目前授予俄亥俄州立大学(OSU)医学博士Michael A.Caligiuri的艾滋病恶性联盟(AMC)赠款的五年竞争续期。在该奖项的过去四年中，该协会是AMC淋巴瘤工作组和AMC实验室工作组的积极参与者。该协会成功地角逐了两项AMC临床试验的相关科学奖，该协会目前主持了一项AMC临床方案，该方案使用一种生物反应调节剂治疗HIV非霍奇金淋巴瘤(NHL)。PI目前正在为AMC开发另外两项临床研究：第一项是在HIV非霍奇金淋巴瘤首次诱导治疗后进行的低剂量白介素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地点合作进行。AMC审查了意向书(LOI)，并向AMC提交了一份议定书。PI提交的第二项研究是II期研究，评估抗CD20单抗对移植后淋巴增生性疾病(PTLD)患者的抗肿瘤活性。PTLD现在将作为一种免疫缺陷性淋巴瘤被纳入AMC议程，这将是AMC内的第一个此类方案。已获AMC批准的意向书和方案已提交。尽管有这些智力上的贡献，俄亥俄州立大学及其前附属机构罗斯韦尔公园癌症研究所的收益却很差，在13个主要AMC网站中排名约第8。因此，为了解决这一弱点，和平协会现在设立了四个新的网站，每个网站都有大量艾滋病毒-1+患者和艾滋病恶性肿瘤患者，每个网站都是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，以及澳大利亚的三家医院组成的财团，这三家医院隶属于一个名为国家艾滋病毒流行病学和临床研究中心(NCHECR)的共同临床研究小组。NCHECR评估和治疗全澳大利亚绝大多数HIV-1和艾滋病恶性肿瘤患者。俄亥俄州立大学的每个附属网站都有独特的优势。一些中心有大量的市中心人口，有大量的妇女和少数族裔患者，而另一些中心有非常强大的I-III期合作小组试验或独特的实验室专业知识的历史。总体而言，这组新的俄亥俄州立大学附属网站应该会给AMC带来几个优势，最显著的是增加AMC治疗HIV NHL和HIV Kaposi肉瘤的协议的收益。已经制定了一项预算，为每个附属网站提供最低基线的支持，以使方案获得机构审查委员会的批准，并开始筛查患者进行研究。然而，在每个站点最初积累四名患者之后，每个站点的资金变得与它们招收患者的能力挂钩。总体而言，与我们之前的应用程序相比，该应用程序在智力贡献和患者收益方面为AMC提供了更强的实力。

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.