Expedited Expansion Cohort Clinical Trial for Relapsed/Refractory 'no-option' Non-Hodgkin's Lymphoma/Leukemia Patients

针对复发/难治性“无选择”非霍奇金淋巴瘤/白血病患者的快速扩展队列临床试验

• 批准号: 10642955
• 负责人: Theresa Deisher
• 金额: $ 100万
• 依托单位: AVM BIOTECHNOLOGY, LLC
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-10 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10642955
• 关键词: Acceleration; Accreditation; Acute; Agreement; Autologous; B-Cell Acute Lymphoblastic Leukemia; Biotechnology; Cancer Center; Cardiotoxicity; Cell Therapy; Cities; Clinical Protocols; Clinical Trials; Cohort Studies; Comprehensive Cancer Center; Data; Desire for food; Dexamethasone; Diagnosis; Disease; Dose; Drops; Enrollment; FDA approved; Formulation; Funding; Future; Glioblastoma; Health; Hematologic Neoplasms; Holden Comprehensive Cancer Center at the University of Iowa; Hospitals; Illinois; In complete remission; Indiana; Label; Malignant Neoplasms; Malignant lymphoid neoplasm; Malignant neoplasm of prostate; Marketing; Medical; New Mexico; Non-Hodgkin' s Lymphoma; Patients; Persons; Pharmaceutical Preparations; Phase; Progressive Disease; Quality of life; Recurrent disease; Refractory; Regimen; Relapse; Reporting; Request for Proposals; Residual Neoplasm; Safety; Salvage Therapy; Second Primary Cancers; Sepsis; Site; Survival Rate; Texas; Therapeutic; Toxic effect; Transplantation; Universities; arm; cancer care; cancer therapy; chemotherapy; chimeric antigen receptor T cells; clinical development; cohort; design; hematopoietic cell transplantation; human old age (65+); improved; innovation; leukemia/lymphoma; novel therapeutics; participant enrollment; patient population; pre-clinical; prevent; response; side effect; standard of care; synergism; treatment center; trial design

ABSTRACT Non-Hodgkin’s Lymphoma (NHL) is the 7th most common cancer in the U.S., with over half of the 77,240 people diagnosed annually over age 65. In about 50% of cases, disease recurs or relapses, typically within two years of initial treatment, and in some patients disease is refractory to additional treatment (Refractory/Relapsed, R/R). Salvage therapy in these patients consists of stronger chemotherapy cocktails or more recently, cell therapy or hematopoietic cell transplantation. Four-year survival rates are about 40% with salvage chemotherapy and 60% for ASCT. Autologous Chimeric Antigen Receptor T (CarT) cell products have triggered great response rates in clinical trials and real-world use for some types of R/R NHL. However, the therapies are not curative with up to 46% relapsing within 2 weeks to 8.5 months even with negative minimal residual disease (MRD); they are associated with significant toxicities and are restricted to administration at accredited treatment centers. AVM Biotechnology’s FDA-approved trial, NCT04329728, is currently ongoing. This clinical trial includes a dose- escalation study of AVM0703 and a pivotal adaptive-design expansion cohort study in no-option patients with lymphoid malignancies who failed at least 1 prior regimen, who do not qualify for any other approved therapy, and who need treatment due to progressive disease. Currently City of Hope, UCLA, Norton Cancer Institute, Levine Cancer Institute, and University of Texas Southwestern are actively enrolling patients. Illinois Cancer Care University of Illinois and Holden Comprehensive Cancer Center at University of Iowa are being activated. Indiana University Melvin and Bren Simon Comprehensive Cancer Center, University of New Mexico Comprehensive Cancer Center, CHI Health St. Francis Hospital, Advent Health Hendersonville, Moffitt Cancer Center and MD Anderson Cancer Center will participate in the expansion cohort phase. Patients dosed to date, in compassionate use and in enrolled dose-escalation cohorts, demonstrate that AVM0703 is distinguished from other investigative drugs in this ‘terminal no-option’ patient population by its absence of safety concerns, and the sites report that their patients feel great, regain appetite and energy, and durable response has been recorded. This proposal requests funding for the adaptive design expansion cohort study. Once the expansion phase dose has been determined (projected for Nov 2021 based on enrollment, safety and response to date) patients will be enrolled in 5 NHL sub-indication specific cohorts, requiring about 18 patients per arm to be able to see significant overall response rates. Adaptive design expansion studies offer a faster way to bring drugs to no-option patients and this expansion study has been specifically designed to meet FDA guidance for a marketing application. In the future AVM0703 will be studied in clinical trials in combination with earlier lines of therapy to determine the potential synergy of AVM0703 with standard of care to enhance complete response rate, reduce relapse rates, and potentially reduce the total number of therapeutic cycles patients require. This could significantly improve acute quality of life by reducing side-effects, reduce medical expenses and reduce long term toxicities.

抽象的 非霍奇金淋巴瘤（NHL）是美国第七大癌症，其中77,240人中有一半以上 每年诊断为65岁以上。在大约50％的病例中，疾病复发或退休，通常在两年内 初始治疗，在某些患者中，疾病是对额外治疗的难治性（难治性/复发，R/R）。 这些患者的打捞疗法包括强烈的化学疗法鸡尾酒，或者最近，细胞疗法或 造血细胞移植。四年生存率约为40％，救助化疗和60％ 对于ASCT。自体嵌合抗原受体T（CART）细胞产品触发了很高的响应率 用于某些类型的R/R NHL的临床试验和现实世界使用。但是，疗法无法治愈 即使患有最小残留疾病（MRD），在2周至8.5个月内复发46％；他们是 与明显的毒性相关，仅限于认可的治疗中心的给药。 AVM生物技术的FDA批准试验NCT04329728目前正在进行中。该临床试验包括剂量 对无选患者 淋巴性恶性肿瘤至少未能接受1个治疗疗法的淋巴恶性肿瘤， 以及由于进行性疾病而需要治疗的人。目前，加州大学洛杉矶分校的希望之城，诺顿癌症研究所， 莱文癌症研究所和德克萨斯大学西南大学正在积极招募患者。伊利诺伊州癌症 爱荷华大学的伊利诺伊州护理大学和霍尔顿综合癌症中心正在被激活。 印第安纳大学梅尔文和布伦·西蒙综合癌症中心，新墨西哥州大学 Chi Health St. Francis医院综合癌症中心，莫菲特癌症 中心和MD安德森癌症中心将参加扩展队列阶段。迄今为止的患者， 在富有同情心的使用和注册的剂量提升同类中，证明了AVM0703与 由于缺乏安全问题，其他调查药物的其他调查药 网站报告说，他们的患者感觉很好，继续食欲和能量，并记录了持久的反应。 该建议要求为自适应设计扩展队列研究提供资金。一旦扩张阶段剂量 已经确定（根据入学率，安全性和迄今为止的响应为2021年11月的预计）患者将是 参加了5个NHL辅助特定人群，每臂需要大约18名患者才能看到显着 总体响应率。自适应设计扩展研究提供了一种更快的方法，可以将药物带到无选患者 这项扩展研究是专门设计的，以满足FDA的营销应用指南。 在将来 AVM0703的潜在协同作用与标准的护理，以提高完整响应率，降低继电器 发生率，并有可能减少患者所需的治疗周期总数。这可能很大 通过减少副作用，减少医疗费用并减少长期毒性来改善急性生活质量。