TAT INHIBITOR (R024-7429) TO TREAT KAPOSI'S SARCOMA

TAT 抑制剂 (R024-7429) 治疗卡波西肉瘤

• 批准号: 2104197
• 负责人: JAMIE H VON ROENN
• 金额: $ 6.94万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-09-30 至 1999-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2104197
• 关键词: AIDS; AIDS therapy; Kaposi's sarcoma; antineoplastics; antiviral agents; biomarker; clinical trials; dosage; enzyme linked immunosorbent assay; human immunodeficiency virus 1; human subject; human therapy evaluation; leukocyte count; medical complication; messenger RNA; neoplasm /cancer chemotherapy; polymerase chain reaction; provirus; quality of life; virus DNA; virus antigen; virus genetics; virus protein

Kaposi's sarcoma (KS) is the most common malignancy associated with HIV- infection. Over the last decade, deaths due to KS have nearly doubled. Opportunistic infection, either alone or in combination with progressive KS, is the leading cause of death. HIV-associated immunosuppression is the basis for this high infection rate, underscoring the urgent need for new therapeutic strategies for AIDS-related KS which incorporate antiretroviral therapy. The purpose of this proposal is to evaluate the tat inhibitor, RO24-7429 in a phase II trial for its potential as both a therapeutic agent for AIDS-related KS and as an antiretroviral agent. The study will be conducted within the Eastern Cooperative Oncology Group and take advantage of its large demographically diverse patient population and extensive experience with clinical trials. The specific aims of this proposal are 1) to investigate an optimal dose of the tat inhibitor, RO24-7429, in patients with AIDS-related KS, and to evaluate the overall and complete response rate of RO24-7429 in these patients, 2) to evaluate its effect on quality of life of patients with AIDS- related KS, 3) to evaluate the antiretroviral activity of RO24-7429 by monitoring CD4 and CD8 lymphocyte subsets, p24 antigen levels, and levels of free virus; and evaluate the molecular effects of RO24-7429 by serially evaluating levels of HIV-1 proviral DNA, spliced tatmRNA and unspliced mRNA (gag) in peripheral blood mononuclear cells by quantitative PCR, and 4) to explore the relationship between the antineoplastic effect and antiretroviral effect of RO24-7429.

Kaposi的肉瘤（KS）是与HIV相关的最常见的恶性肿瘤 感染。 在过去的十年中，由于KS而导致的死亡几乎翻了一番。 机会性感染，无论是单独还是与渐进式感染 KS是死亡的主要原因。 与HIV相关的免疫抑制是 高感染率的基础，强调了迫切需要 与AIDS相关的KS的新治疗策略，该策略合并 抗逆转录病毒疗法。 该提议的目的是评估 TAT抑制剂，RO24-7429在II期试验中的潜力 与AIDS相关的KS的治疗剂和抗逆转录病毒剂。 该研究将在东方合作肿瘤学组内进行 并利用其大量人口多样的患者 人口和临床试验的丰富经验。 具体 该提案的目的是1）研究TAT的最佳剂量 抑制剂RO24-7429，与AIDS相关KS的患者，并评估 在这些患者中，RO24-7429的总体和完全缓解率， 2）评估其对艾滋病患者生活质量的影响 - 相关KS，3）评估RO24-7429的抗逆转录病毒活性 监测CD4和CD8淋巴细胞亚群，P24抗原水平以及水平 自由病毒；并评估RO24-7429的分子效应 串行评估HIV-1病毒DNA，剪接的tatmRNA和 未经贴花的mRNA（GAG）在外周血单核细胞中 定量PCR和4）探索 RO24-7429的抗塑性作用和抗逆转录病毒作用。