A Randomized Phase II Clinical trial to Determine the Safety, Tolerability and Ef

确定安全性、耐受性和疗效的随机 II 期临床试验

基本信息

  • 批准号:
    7729554
  • 负责人:
  • 金额:
    $ 14.16万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2008
  • 资助国家:
    美国
  • 起止时间:
    2008-09-11 至 2011-08-31
  • 项目状态:
    已结题

项目摘要

There are no treatments available to men with non-metastatic hormone-refractory (NMHR) prostate cancer (PC). For such patients immunotherapy may be beneficial. This proposal aims to enhance the clinical effectiveness of therapeutic vaccination against PC and test it in patients in the NMHR stage such that progression to metastatic hormone-refractory prostate cancer (HRPC) may be delayed. The study aims to combine two hitherto separately applied modes of immunotherapy: vaccination with autologous dendritic cells and vaccination with allogeneic PC cells (APCCs). Recently our collaborators reported that a vaccine consisting solely of APCCs reduced PSA velocity in 42 percent of patients and extended the median time to progression in men suffering from NMHR-PC to 58 weeks compared to historical controls of 26 weeks (Michael et al., Clin Cancer Res, 11: 4469-4478; 2005). We hypothesize that clinical efficacy of this APCC vaccine will be enhanced by combination with fully mature autologous myeloid dendritic cells (amDCs) that are engineered to secrete IL-6 and IL-12; these cytokines are expected to stimulate expansion of cytotoxic T cells over the suppressing T regulatory cells. The specific aims of this study are: 1) To conduct a two-arm randomized phase 2 clinical trial of the APCC vaccine administered alone (Arm I) or in combination with amDCs (Arm II) to patients suffering from NHHR-PC. Based on our recent findings that human serum kallikrein-2 (hK2) levels correlate with overall survival in patients suffering from HRPC, we will determine the role of hK2 as a survival predictor in HRPC patients treated with immunotherapy. 2) To identify and characterize the type, extent, and duration of the immune response in patients treated in Arm I and Arm II. We will enroll 30 patients to each arm of this open-label phase 2 trial. Metastasis-free survival is the primary endpoint, while vaccine toxicity and tolerability, PSA-based progression-free survival, change in PSA velocity and duration of PSA response, changes in the predictive survival score and changes of immune function are among secondary endpoints. The proposed trial combines the advantages of APCCs as a source of tumor antigens with DCs that present antigens both to CD4+ and CD8+ T cells. The applicants are fully equipped, trained and experienced in clinical grade manufacturing of APCCs and DCs and have tested them in earlier separate clinical trials assuring timely initiation and technical success of the study.
非转移性激素耐药(NMHR)前列腺癌的男性尚无治疗方法 (PC)。对于这样的患者,免疫治疗可能是有益的。这项建议旨在提高临床 治疗性接种前列腺癌疫苗的效果,并在NMHR阶段的患者中进行测试,以便 转移性激素难治性前列腺癌(HRPC)的进展可能会延迟。这项研究旨在 结合两种迄今单独应用的免疫治疗模式:自体树突状细胞疫苗接种 细胞和用异基因PC细胞(APCCs)接种。最近,我们的合作者报告说,一种疫苗 在42%的患者中,仅由APCCs组成的PSA速度降低,中位时间延长至 患有NMHR-PC的男性患者进展至58周,而历史对照组为26周 (Michael等人,《临床癌症研究》,11:4469-4478;2005)。我们假设这种APCC的临床疗效 疫苗将通过与完全成熟的自体髓系树突状细胞(AmDC)相结合而得到增强 被设计成分泌IL-6和IL-12;这些细胞因子有望刺激细胞毒性T细胞的扩张 抑制T调节细胞上的细胞。本研究的具体目的是:1)进行双臂 APCC疫苗单独接种(ARM I)或联合应用的随机2期临床试验 AMDC(ARM II)用于NHHR-PC患者。根据我们最近的发现,人类血清 激肽释放酶-2(HK2)水平与HRPC患者的总生存期相关,我们将确定 HK2在接受免疫治疗的HRPC患者中作为生存预测因子的作用。2)识别和 描述接受ARM I和ARM II治疗的患者的免疫反应的类型、程度和持续时间。 在这项开放标签的第二阶段试验中,我们将为每组患者招募30名患者。无转移生存是首要的 终点,虽然疫苗的毒性和耐受性、基于PSA的无进展生存率、PSA的变化 PSA反应的速度和持续时间、预测生存评分的变化和免疫的变化 函数属于次要端点。拟议的试验结合了APCCs作为一项 肿瘤抗原的来源,DC同时向CD4+和CD8+T细胞呈递抗原。申请者是 设备齐全,训练有素,有临床级APCCs和DC的制造经验,并已进行过测试 他们在早期的单独临床试验中,确保了研究的及时启动和技术成功。

项目成果

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STANIMIR VUK-PAVLOVIC其他文献

STANIMIR VUK-PAVLOVIC的其他文献

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{{ truncateString('STANIMIR VUK-PAVLOVIC', 18)}}的其他基金

A Randomized Phase II Clinical trial to Determine the Safety, Tolerability and Ef
确定安全性、耐受性和疗效的随机 II 期临床试验
  • 批准号:
    8128728
  • 财政年份:
  • 资助金额:
    $ 14.16万
  • 项目类别:
A Randomized Phase II Clinical trial to Determine the Safety, Tolerability and Ef
确定安全性、耐受性和疗效的随机 II 期临床试验
  • 批准号:
    7919517
  • 财政年份:
  • 资助金额:
    $ 14.16万
  • 项目类别:

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