CLINICAL TRIAL: ADMINISTRATION OF LMP1- AND LMP2-SPECIFIC CYTATOXIC T-LYMPHOCYTE

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 摘要 这项I期剂量递增试验旨在评估自体LMP1和LMP2特异性CTL递增剂量的安全性。在T细胞治疗的新试验设计中，我们一直在使用一种改进的持续再评估方法(MCRM)。我们使用这种基于模型的适应性设计的基本原理来自于我们在这些细胞抑制疗法方面的丰富经验，与细胞毒剂不同，这些疗法在所建议的剂量范围内具有浅的剂量-毒性分布。因此，加速剂量递增的设计不应损害患者的安全。基于之前T细胞免疫治疗试验的模拟表明，这种设计提供了更高的概率宣布适当的剂量为MTD，并允许在较低的甚至可能是次优的剂量水平下积累较少的患者。更重要的是，我们的模拟表明，与标准的3+3设计相比，使用mCRM策略不会导致毒性增加。 不设随机化或对照组。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. ABSTRACT This Phase I dose-escalation trial is designed to evaluate the safety of escalating doses of autologous LMP1- and LMP2-specific CTL. We have been using a modified version of the continual reassessment method (mCRM) in the design of new trials on T-cell based therapies. Our rationale for the use of this model-based, adaptive design stems from our considerable experience with these cytostatic therapies, which unlike cytotoxic agents, have shallow dose-toxicity profiles over the range of doses proposed. As such, designs with more accelerated dose escalations should not compromise the safety of our patients. Simulations based on previous T-cell immunotherapy trials, indicate that this design provides higher probabilities of declaring the appropriate dose as the MTD and allows smaller numbers of patients to be accrued at lower and possibly suboptimal dose levels. More importantly, our simulations indicate that use of the mCRM strategy will not lead to increased toxicities, compared with standard 3+3 designs. There is no randomization or control groups.