A Phase 1, Open Label, Multicenter Trial to Assess the Safety, Tolerability and Efficacy of MB-106 in Patients with Relapsed or Refractory CD20+ B-Cell NHL or CLL

一项 1 期、开放标签、多中心试验，旨在评估 MB-106 在复发或难治性 CD20 B 细胞 NHL 或 CLL 患者中的安全性、耐受性和有效性

• 批准号: 10489813
• 负责人: Manuel Litchman
• 金额: $ 99.93万
• 依托单位: MUSTANG BIO, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-16 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10489813
• 关键词: Antigens; Autologous; B lymphoid malignancy; B-Cell Lymphomas; B-Cell NonHodgkins Lymphoma; B-Lymphocytes; Binding; Blood; Bone Marrow; CAR T cell therapy; CD19 gene; CD28 gene; CD4 Positive T Lymphocytes; CD8-Positive T-Lymphocytes; Cell Therapy; Cellular immunotherapy; Chronic; Chronic Lymphocytic Leukemia; Clinical; Clinical Trials; Collection; Disease; Disease remission; Dose; Elements; Enrollment; Fc Receptor; Fred Hutchinson Cancer Research Center; Future; Genetic; Human; Immunotherapy; Incidence; Individual; Infusion procedures; Intervention; Investigational Drugs; Left; Lentivirus Vector; Leukapheresis; Ligands; Lymphatic; Lymphoma; MS4A1 gene; Malignant Neoplasms; Measures; Methodology; Multi-Institutional Clinical Trial; Multicenter Trials; Mus; Non-Hodgkin' s Lymphoma; Organ; Patients; Peripheral Blood Mononuclear Cell; Phase; Phase I Clinical Trials; Phase II Clinical Trials; Phenotype; Preclinical Testing; Productivity; Protocols documentation; Quality of life; Receptor Gene; Refractory; Relapse; Research; Research Subjects; Role; Safety; Scientist; Severities; Site; Small Business Innovation Research Grant; T cell therapy; T-Lymphocyte; TCF3 gene; Testing; Therapeutic; Time; anti-CD20; base; cellular engineering; cellular transduction; chimeric antigen receptor; chimeric antigen receptor T cells; curative treatments; cytokine; cytokine release syndrome; dosage; efficacy testing; genetically modified cells; innovation; manufacturing process; molecular targeted therapies; neurotoxicity; open label; plasmid DNA; primary endpoint; promoter; prototype; receptor; response; treatment group; tumor; vector

ABSTRACT In this application, we propose to optimize the feasibility of Mustang Bio's propriety MB-106 and its impact on B- cell Non-Hodgkin's Lymphoma (NHL) and Chronic Lymphatic Lymphoma (CLL) patients and determine an optimal dosage for patients with relapsed or refractory CD20+ B-cell NHL or CLL. While the current courses of molecular targeted therapies have resulted in prolonged remissions, to date there is no curative therapeutic for NHL and CLL cancers. Therefore, an innovative approach is needed for an individualized and specific therapy that can persist past remission dates. CAR T cell therapy such as proposed here, is a cellular immunotherapy that uses adoptive T-cells expressing a chimeric antigen receptor specific to targeting tumor-associated B- cell antigens. The methodology proposed is highly individualized, as each product is manufactured individually for each patient. In this Direct to Phase 2 clinical trial, MB-106 will be tested for efficacy, safety, and determine the optimal dosage for patients. Proposed is an open-label interventional, non-randomized adoptive T-cell immunotherapy study to broaden the understanding the impact of MB-106 in blood, bone marrow, and other sites of disease measured by cytokine levels post infusion. At the conclusion of this project, the recommended dosage of MB-106 for patients will be determined and will be used as the basis for treatment in future clinical trials and ultimate clinical use.

摘要 在本申请中，我们建议优化Mustang Bio专有MB-106的可行性及其对B- 细胞非霍奇金淋巴瘤（NHL）和慢性淋巴瘤（CLL）患者，并确定一个 复发性或难治性CD 20 + B细胞NHL或CLL患者的最佳剂量。 虽然目前的分子靶向治疗疗程已导致长期缓解，但迄今为止， 对NHL和CLL癌症没有治愈性治疗。因此，需要一种创新的方法， 个体化和特定的治疗，可以持续过去缓解日期。CAR T细胞疗法，例如 在此，是一种细胞免疫疗法，其使用表达嵌合抗原受体的过继性T细胞，所述嵌合抗原受体特异于 靶向肿瘤相关B细胞抗原。所提出的方法是高度个性化的，因为每个产品 为每位患者单独制造。 在这项直接进入2期临床试验中，MB-106将被测试有效性、安全性，并确定最佳剂量。 对患者拟定的是一项开放标签干预性、非随机过继性T细胞免疫治疗研究， 拓宽对MB-106在血液、骨髓和其他疾病部位中的影响的理解 通过输注后细胞因子水平。在该项目结束时， 将确定患者，并将其用作未来临床试验和最终临床试验的治疗基础。 使用.