Biostatistics and Data Management

项目摘要 异基因造血干细胞移植(HSCT)是一种历史悠久的血液恶性肿瘤治疗方法。 HSCT的治疗益处和潜在治愈是由移植物抗肿瘤(GVT)效应介导的， 来自供体免疫系统。本计划项目研究项目的总体目标 因此，应用是为了增强这种GVL对复发的高危患者的效果，通过使用 免疫调节，目标是开发选择性增强肿瘤免疫和 改善患者的预后。具体地说，项目1将专注于新的免疫疗法的临床试验，这些疗法 旨在利用全白血病细胞疫苗预先增强移植后的免疫反应性， 新抗原/次要组织相容性抗原(MHAgs)接种或检查点阻断抑制物或治疗 使用Treg耗尽的供者淋巴细胞输注加检查点阻断抑制剂进行复发。项目2将 探讨GVL的发病机制及对新抗原/mHAgs的特异性T细胞反应 在项目1中进行的临床试验中产生的疫苗接种。项目3将侧重于克隆的影响 供体干细胞产品中的造血(芯片)对移植后临床和免疫学结果的影响。这个 生物统计和数据管理核心(核心1)的主要目标是提供统计协作 所有参与该计划项目的调查人员。这包括与项目调查人员在 项目1的临床试验设计和项目2和3的实验室研究，临床和实验室分析 数据，并在项目1-3中建立临床结果与实验室结果的相关性，并参与 在所有项目中撰写手稿。核心一号还将提供集中机制，以确保及时和 完全捕获此计划项目中的所有临床数据。这包括收集和维护 必要的临床信息、数据管理支持、临床数据质量控制和临床监督 试运行，以确保及时收集每项协议所需的所有数据要素；以及 必要时，设计研究程序和数据库，以便进行盲目的实验室评估和 随后与患者级别的数据集成以进行分析。 PHS 398/2590(11/07版)页面续格式页面

Project Summary Allogeneic hematopoietic stem cell transplantation (HSCT) is a long-established therapy for blood malignancies. The therapeutic benefit and potential cure achieved by HSCT is mediated by the graft-vs-tumor (GVT) effect that is derived from donor immune system. The overarching objective of the research projects in this Program Project application is thus to enhance this GVL effect for high risk patients for relapse by administering subsequent immunomodulation with the goal of developing novel strategies for selectively enhancing tumor immunity and improving patient outcomes. Specifically, Project 1 will focus on clinical trials for novel immunotherapies that are designed to enhance post-transplant immune reactivity pre-emptively using whole leukemia cell vaccination, neoantigen/minor histocompatibility antigens (mHAgs) vaccination or check point blockade inhibitor or to treat relapse using Treg depleted donor lymphocyte infusion plus check point blockade inhibitor. Project 2 will investigate the underlying mechanisms of GVL and the specific T cell responses to neoantigen/mHAgs vaccination generated in clinical trials carried out in Project 1. Project 3 will focus on the impact of clonal hematopoiesis (CHIP) in the donor stem cell product on clinical and immunologic outcomes after transplant. The primary objective of the Biostatistics and Data Management Core (Core 1) is to provide statistical collaboration for all investigators involved in this Program Project. This includes collaboration with project investigators in the design of clinical trials in Project 1 and laboratory studies in Projects 2 and 3, analysis of clinical and laboratory data and to establish correlations of clinical outcomes with laboratory results in Projects 1-3, and participate in manuscript writing in all Projects. Core 1 will also provide centralized mechanisms to assure the timely and complete capture of all clinical data in this Program Project. This includes collection and maintenance of necessary clinical information, data management support, quality control for clinical data, and oversight of clinical trial operations to ensure that all data elements required by each protocol are collected in timely fashion; and where necessary, design of research procedures and databases to allow blinded laboratory assessments and later integration with patient-level data for analysis. PHS 398/2590 (Rev. 11/07) Page Continuation Format Page