MSKCC BMT CTN Renewal

MSKCC BMT CTN 更新

基本信息

批准号：
10187629
负责人：
MIGUEL-ANGEL PERALES
金额：
$ 20.01万
依托单位：
SLOAN-KETTERING INST CAN RESEARCH
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-09-30 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10187629
关键词：
Accreditation Acute Lymphocytic Leukemia Adoptive Cell Transfers Adoptive Transfer Adult Adverse event Autologous B-Cell NonHodgkins Lymphoma B-Lymphocytes Blood Bone Marrow Transplantation CD19 gene CD28 Antigens Cell Therapy Cells Cellular immunotherapy Childhood Clinical Clinical Services Clinical Trials Clinical Trials Network Combination Drug Therapy Comprehensive Cancer Center Correlative Study Country Disease Disease Resistance Disease-Free Survival Dose Effectiveness Enrollment Future Gene-Modified Genes Genetic Engineering Goals Grant Hematological Disease Hematology Hematopoietic Stem Cell Transplantation Immune Infusion procedures Leadership Lymphoma Malignant - descriptor Malignant lymphoid neoplasm Memorial Sloan-Kettering Cancer Center Mission Multi-Institutional Clinical Trial Neurologic Non-Hodgkin&apos s Lymphoma Non-Malignant Oncology Outcome Participant Patient Care Patient-Focused Outcomes Patients Pilot Projects Progression-Free Survivals Progressive Disease Protocols documentation Radiation therapy Randomized Recurrent disease Refractory Relapse Research Research Personnel Resistance Risk Safety Schedule Scientist Serum Services Signal Transduction Structure T-Cell Receptor T-Lymphocyte Testing Time Toxic effect Transplant Recipients Tumor Antigens Work arm chemotherapy chimeric antigen receptor chimeric antigen receptor T cells clinical center cytokine cytotoxic design disorder control early phase trial experience genetically modified cells hematopoietic cell transplantation high risk improved improved outcome innovation large cell Diffuse non-Hodgkin&apos s lymphoma member next generation novel phase 2 study phase I trial phase II trial preclinical study primary endpoint programs randomized trial receptor standard of care success transplantation therapy

项目摘要

Project Summary/Abstract The mission of the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) is to “advance hematopoietic cell transplantation (HCT) for patients with rare and difficult to treat blood diseases through high- quality multi-center clinical trials by evaluating new ways to improve traditional HCT approaches or by advancing HCT therapy through the use of either novel ex vivo manipulated cell products or genetically- modified cells.” Memorial Sloan Kettering Cancer Center (MSK) is an NCl-designated Comprehensive Cancer Center with one of the largest HCT programs in the country. The HCT program at MSK is FACT-accredited program and divided into pediatric and adult services. MSK has been a Core Member of the BMT CTN since its inception and Dr. Perales (Deputy Service Chief, grant PI), Dr. Giralt (Adult BMT Service Chief, former PI) as well as all members of the Adult BMT Service consider participation in the BMT CTN an integral part of their mission. In this grant, we detail our ongoing commitment to the success of the Network through the formation of an oversight structure that includes a BMT CTN MSK Executive Committee, a BMT CTN Protocol Management Team, and a BMT CTN Internal Advisory Board. These three administrative structures leverage not only the senior leadership of the clinical services in the Division of Hematologic Oncology, but also some of MSK's most outstanding scientists and investigators. We are also committed to continue to provide leadership to the Network with the next generation of innovative trials and correlative studies. In particular, we propose a multicenter randomized phase II trial to determine the safety and efficacy of post-HCT administration of CD19 targeted chimeric antigen receptor (CAR) T cells in patients undergoing high-dose therapy followed by autologous HCT (HDT-AHCT) for relapsed/refractory (rel/ref) DLBCL. We propose 3 specific aims: (1) Demonstrate that MSK has the clinical and translational expertise, and capabilities in novel cell therapies, genetically-modified cells, and early phase trials to fulfill the obligations of a BMT CTN Core Clinical Center that will move forward the BMT CTN mission and goals; (2) Complete a phase II study in which rel/ref DLBCL patients will receive 3 monthly infusions of CD19 CAR T cells after HDT-AHCT. In Arm 1, the 1st infusion will be day +3 after HCT, with later infusions on days +30 and +60. In Arm 2, the 1st infusion will be day +10, with later infusions on the same Arm 1 schedule. The primary endpoint will be PFS at a 1-year. A pick-the-winner design will be used for the study; (3) Assess quantitative persistence and qualitative function of CAR T cells and correlate to: serum cytokine profiles, B cell aplasia, and clinical outcomes. This research is significant as it proposes a novel treatment paradigm in patients with relapsed DLBCL resistant to standard-dose 2nd-line chemotherapy, who typically would have long-term EFS with HDT-AHCT of only 10-15%. The proposed study is highly relevant to the BMT CTN, since it presents an innovative cell therapy, u s i n g genetically modified cells to improve outcomes in patients with advanced lymphoid malignancies, including rel/ref DLBCL.

项目概要/摘要血液和骨髓移植临床试验网络 (BMT CTN) 的使命是“推进造血细胞移植（HCT）针对罕见且难以治疗的血液疾病患者，通过高通过评估改进传统 HCT 方法的新方法或通过通过使用新型离体工程细胞产品或基因疗法来推进 HCT 疗法改良细胞。”纪念斯隆凯特琳癌症中心 (MSK) 是 NCl 指定的综合癌症中心 MSK 斯隆的 HCT 项目已获得 FACT 认证，该中心拥有全国最大的 HCT 项目之一。计划并分为儿科和成人服务，自那时以来 MSK 一直是 BMT CTN 的核心成员。其成立以及 Perales 博士（副服务主管、授予 PI）、Giralt 博士（成人 BMT 服务主管、前 PI）以及成人 BMT 服务的所有成员都认为参与 BMT CTN 是其工作的一个组成部分在这笔赠款中，我们详细说明了我们对通过组建网络取得成功的持续承诺。监督结构包括 BMT CTN MSK 执行委员会、BMT CTN 协议管理团队和 BMT CTN 内部顾问委员会利用这三个管理结构。不仅是血液肿瘤科临床服务的高级领导，还有一些我们还致力于继续发挥 MSK 最杰出的科学家和研究人员的领导作用。我们特别向该网络提出了下一代创新试验和相关研究。确定 HCT 后给予 CD19 的安全性和有效性的多中心随机 II 期试验接受高剂量治疗的患者中的靶向嵌合抗原受体 (CAR) T 细胞，然后自体 HCT (HDT-AHCT) 治疗复发/难治性 (rel/ref) DLBCL 我们提出 3 个具体目标：(1) 证明 MSK 斯隆拥有临床和转化专业知识以及新型细胞疗法的能力，转基因细胞和早期试验，以履行 BMT CTN 核心临床中心的义务 (2) 完成一项 II 期研究，其中 rel/ref DLBCL HDT-AHCT 后，患者将接受 3 个月的 CD19 CAR T 细胞输注。在第 1 组中，第一次输注将是。 HCT 后第 +3 天，稍后在第 +30 天和 +60 天进行输注在第 2 组中，第一次输注将在第 +10 天，稍后进行。相同 Arm 1 时间表的输注将是 1 年的 PFS。 (3) 评估CAR T细胞的定量持久性和定性功能与以下因素相关：血清细胞因子谱、B 细胞发育不全和临床结果。这项研究意义重大。为对标准剂量二线耐药的复发性 DLBCL 患者提出了一种新的治疗模式化疗，HDT-AHCT 的长期 EFS 通常仅为 10-15%。与 BMT CTN 高度相关，因为它提供了一种创新的细胞疗法，主要使用转基因技术细胞可改善晚期淋巴恶性肿瘤患者的预后，包括 rel/ref DLBCL。