Biostatistics and Data Management

生物统计学和数据管理

• 批准号: 10465098
• 负责人: Haesook T Kim
• 金额: $ 28.26万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-14 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10465098
• 关键词: Allogenic; Biometry; Blinded; Blood; Clinical; Clinical Data; Clinical Research; Clinical Trials; Clinical Trials Design; Collaborations; Collection; Data; Data Analyses; Data Element; Databases; Donor Lymphocyte Infusion; Ensure; Goals; Graft vs Tumor Effect; Hematopoiesis; Hematopoietic Stem Cell Transplantation; Immune; Immune system; Immunologics; Immunotherapy; Laboratories; Laboratory Research; Laboratory Study; Leukemic Cell; Maintenance; Malignant Neoplasms; Manuscripts; Mediating; Minor Histocompatibility Antigens; Outcome; Patient-Focused Outcomes; Patients; Procedures; Protocols documentation; Quality Control; Regulatory T-Lymphocyte; Relapse; Research Design; Research Personnel; Research Project Grants; Services; T cell response; Therapeutic; Time; Transplantation; Tumor Immunity; Vaccination; Writing; data management; design; donor stem cell; graft vs leukemia effect; high risk; immune checkpoint blockade; immunoregulation; improved; inhibitor; neoantigens; novel; novel strategies; operation; post-transplant; programs; relapse patients; research study

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

项目摘要 异基因造血干细胞移植（HSCT）是治疗血液恶性肿瘤的一种长期有效的方法。 通过HSCT实现的治疗益处和潜在治愈是由移植物抗肿瘤（GVT）效应介导的， 来源于供体免疫系统。本计划项目研究项目的总体目标 因此，本申请的目的是通过施用随后的药物来增强这种GVL对复发的高风险患者的作用。 免疫调节，目的是开发选择性增强肿瘤免疫的新策略， 从而改善患者结果。具体来说，项目1将专注于新型免疫疗法的临床试验， 设计为使用全白血病细胞疫苗接种预先增强移植后免疫反应性， 新抗原/次要组织相容性抗原（mHAgs）疫苗接种或检查点阻断抑制剂或治疗 使用Treg耗尽的供体淋巴细胞输注加检查点阻断抑制剂治疗复发。项目2将 研究GVL的潜在机制和对新抗原/mHAgs的特异性T细胞应答 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 造血干细胞（CHIP）对移植后临床和免疫结果的影响。的 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 所有参与本项目的研究者。这包括与项目调查人员合作， 项目1中的临床试验和项目2和3中的实验室研究的设计，临床和实验室分析 数据，并在项目1-3中建立临床结局与实验室结果的相关性，并参与 在所有项目中写作。核心1还将提供集中机制，以确保及时和 完整采集本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，以确保及时收集每个方案所需的所有数据元素;以及 必要时，设计研究程序和数据库，以进行设盲实验室评估， 随后与患者级别数据集成进行分析。 PHS 398/2590（Rev. 11/07）