BIOLOGIC MODIFIER THERAPIES IN AIDS MALIGNANCIES

本申请是艾滋病防治联盟（AMC）资助的五年竞争性更新，目前授予迈克尔A。Caligiuri，医学博士在俄亥俄州州立大学（OSU）。 在过去的四年中，PI是AMC淋巴瘤工作组和AMC实验室工作组的积极参与者。 PI成功地竞争了两项AMC临床试验的相关科学奖，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HIV NHL首次诱导治疗后低剂量白细胞介素（IL）2的随机试验。 这项研究可能会与欧洲的行业和艾滋病恶性肿瘤研究中心合作进行。 AMC审查了意向书（LOI），并向AMC提交了方案。PI提交的第二项研究是一项II期研究，评估抗CD 20单克隆抗体对移植后淋巴增生性疾病（PTLD）患者的抗肿瘤活性。 PTLD现在将作为免疫缺陷淋巴瘤纳入AMC议程，这将是AMC内的第一个此类协议。 LOI已获得AMC批准，方案已提交。 尽管有这些知识贡献，俄勒冈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很差，在13个主要AMC站点中排名第8。 因此，为了解决这一弱点，PI现在已经加入了四个新的研究中心，每个研究中心都有大量的HIV-1+患者和艾滋病恶性肿瘤患者，每个研究中心都是AMC的新成员。 PI不再隶属于罗斯韦尔公园。 这四个新站点包括马里兰州大学癌症中心、埃默里大学布雷迪纪念医院、纽约的圣文森特综合癌症中心，以及澳大利亚的三家医院组成的联盟，这些医院在一个名为国家艾滋病流行病学和临床研究中心（NPR）的共同临床研究小组下运作。 NIGER评估和治疗澳大利亚绝大多数HIV-1和艾滋病恶性肿瘤患者。每一个俄勒冈州立大学附属网站都有独特的优势。 一些中心有大量的内城人口，有大量的妇女和少数民族患者，而其他中心有非常强大的I-III期合作组试验或独特的实验室专业知识的历史。 总的来说，这一新的OSU附属研究中心组应该为AMC带来几个优势，最值得注意的是增加了AMC方案对HIV NHL和HIV卡波西肉瘤的应计费用。 已构建预算，为每个附属研究中心提供最低限度的支持基线，以获得机构审查委员会批准的方案，并开始筛选研究患者。 然而，在每个研究中心最初增加4名患者后，每个研究中心的资金将与其增加患者的能力挂钩。 总的来说，与我们以前的应用程序相比，该应用程序为AMC提供了更强的智力贡献和患者累积。

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.