CLINICAL TRIAL OF AN IMPROVED MELANOMA VACCINE

描述：(申请人摘要)申请人的长期目标是 开发一种治疗恶性黑色素瘤的有效疫苗。作为一部分 在这一过程中，他已经完成了临床前研究，表明了一种有效的 提高他的黑色素瘤疫苗有效性的方法是使用 新型佐剂QS-21。他希望利用这一新机会。 实验室开发以调查QS-21是否会改善 一种现有黑色素瘤疫苗的效力和临床疗效 这在临床试验中显示了有希望的结果。具体目标 1)进行第二期临床试验，以确定 多价黑色素瘤抗原疫苗的免疫原性可增强 通过将疫苗与QS-21混合。32例AJCC分期的临床分析 IV(播散性疾病)黑色素瘤将随机接受以下治疗 黑色素瘤疫苗混合标准佐剂(明矾)或 三种不同剂量的QS-21(25ug、50ug或75ug/次免疫) 站点)。在之前和之后的两次固定时间间隔 疫苗免疫、抗黑色素瘤B细胞和T细胞反应 不同的患者群体将被比较。的多个参数 体液和细胞免疫反应将被测量，因为QS-21可能 对这些有不同的影响以及该佐剂的作用机制 需要阐明；2)确定最佳生物剂量 QS-21，最大限度地增强这些反应；3)评估 毒性；4)该疗法的临床疗效。

DESCRIPTION: (Applicant's Abstract) The applicant's long term goal is to develop an effective vaccine to treat malignant melanoma. As part of this process, he has completed preclinical studies that show a potent way of increasing the effectiveness of his melanoma vaccine is to use QS-21, a novel adjuvant. He wishes to take advantage of this new development in the laboratory to investigate whether QS-21 will improve the potency and clinical effectiveness of an existing melanoma vaccine which has shown promising results in clinical trials. Specific aims are: 1) To conduct a Phase II clinical trial, to determine whether the immunogenicity of a polyvalent melanoma antigen vaccine can be increased by admixing the vaccine with QS-21. Thirty-two patients with AJCC stage IV (disseminated disease) melanoma will be randomized to treatment with melanoma vaccine admixed with a standard adjuvant (alum) or with one of three different dose levels of QS-21 (25ug, 50ug, or 75ug/immunization site). On two occasions prior to, and at fixed intervals following vaccine immunization, antimelanoma B and T cell responses in the different groups of patients will be compared. Multiple parameters of the humoral and cellular immune responses will be measured since QS-21 may affect these differently and the mechanism of action of this adjuvant needs to be elucidated; 2) Determine the optimal biological dose of QS-21 that maximally potentiates each of these responses; 3) Evaluate the toxicity, and; 4) The clinical effectiveness of this treatment.