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

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 子项目的主要研究者可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 表示子项目使用的中心基础设施的估计数量， NCRR赠款不直接向子项目或子项目工作人员提供资金。 摘要 这项I期剂量递增试验旨在评估递增剂量的自体LMP 1和LMP 2特异性CTL的安全性。我们一直在使用修改后的持续再评估方法（mCRM）设计基于T细胞疗法的新试验。我们使用这种基于模型的适应性设计的理由源于我们对这些细胞抑制疗法的大量经验，与细胞毒性药物不同，这些疗法在拟定剂量范围内具有较浅的剂量毒性特征。因此，加速剂量递增的设计不应损害患者的安全性。基于先前的T细胞免疫治疗试验的模拟表明，这种设计提供了将适当剂量宣布为MTD的更高概率，并允许在较低和可能次优的剂量水平下累积较少数量的患者。更重要的是，我们的模拟表明，与标准3+3设计相比，使用mCRM策略不会导致毒性增加。 没有随机分组或对照组。

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.