CLINICAL TRIAL: SGN-40 (ANTI-HUCD40 MAB) IN PATIENTS WITH NON-HODGKIN'S LYMPHOMA

临床试验：SGN-40（抗 HUCD40 MAB）在非霍奇金淋巴瘤患者中的应用

• 批准号: 7717874
• 负责人: RAJ ADVANI
• 金额: $ 0.08万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-12-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7717874
• 关键词: Adult; Affect; Age; Antigens; B lymphoid malignancy; B-Lymphocytes; Blood; Blood Vessels; Bone Marrow; Cell surface; Chemotherapy-Oncologic Procedure; Clinical; Clinical Trials; Computer Retrieval of Information on Scientific Projects Database; Dendritic Cells; Disease; Dose; Dose-Limiting; End Point; Endothelial Cells; Epithelial Cells; Funding; Goals; Grant; Human; Incidence; Indolent; Institution; Lymphocyte; Lymphoma; Malignant Neoplasms; Mature B-Lymphocyte; Maximum Tolerated Dose; Monoclonal Antibodies; Nervous system structure; Non-Hodgkin' s Lymphoma; Organ; Patients; Phase I Clinical Trials; Prevalence; Radiation therapy; Rate; Relapse; Research; Research Personnel; Resources; Safety; Source; Spleen; Staging; Stem cell transplant; TNFRSF5 gene; Toxic effect; Tumor Necrosis Factor-alpha; Tumor Necrosis Factors; United States; United States National Institutes of Health; chemotherapy; human TNF protein; lymph nodes; lymphocyte proliferation; member; monocyte; novel; prognostic; receptor; tumor

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Hypothesis: The objectives of this Phase I study with patients with non-Hodgkin's lymphoma (NHL) are: 1. To define the safety profile of 4 weekly doses of an anti-human CD40 monoclonal antibody, SGN-40 2. To determine the maximum tolerated dose of 4 weekly doses of SGN 3. To obtain preliminary anti-tumor activity of SGN-40 Goals: NHL is a heterogeneous malignancy originating from lymphocytes. In the United States, the incidence is estimated at about 54,000/yr with a prevalence of approximately 331,000. The majority (80%) of lymphoma cases is of B-cell origin. While the disease can occur in all ages, the incidence increases with age, with the usual onset beginning in adults over 40 years. NHL is characterized by a clonal proliferation of lymphocytes that accumulate in the lymph nodes, blood, bone marrow, and spleen, although any major organ may be involved. NHL can be divided into two prognostic groups: indolent and aggressive. Intensive combination chemotherapy regimens cure some cases of the aggressive forms of NHL. The more indolent and follicular forms of the disease that affect nearly half of all patients with NHL are considered incurable. While indolent NHL is responsive to radiation therapy and chemotherapy, a continuous rate of relapse is usually seen in advanced stages. In patients who have relapsed from primary treatment and who are not candidates for stem cell transplantation, novel therapies that can provide clinical benefit are needed. The expression of CD40, a member of the tumor necrosis factor (TNF) superfamily, on aggressive NHL makes this antigen an attractive target for treatment of relapsed patients. CD40 is a receptor molecule on the cell surface of all mature B cells (B lymphocytes), most B-cell malignancies, monocytes, dendritic cells (in the nervous system), endothelial cells (within blood vessels), and epithelial cells. Endpoints: This is a Phase I study, and as such endpoints will include: + Defining the safety profile [dose limiting toxicity (DLT)] of 4 weekly doses of SGN-40 in patients with NHL + Determining the maximum tolerated dose (MTD) of 4 weekly doses of SGN-40 in patients with NHL + Obtaining preliminary anti-tumor activity of SGN-40 in patients with NHL

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 假设： 这项在非霍奇金淋巴瘤（NHL）患者中进行的I期研究的目的是： 1. 确定抗人CD 40单克隆抗体SGN-40每周4次给药的安全性特征 2. 确定SGN每周4次给药的最大耐受剂量 3. 获得SGN-40的初步抗肿瘤活性 目标： NHL是一种起源于淋巴细胞的异质性恶性肿瘤。在美国，发病率估计约为54，000/年，患病率约为331，000。大多数（80%）淋巴瘤病例是B细胞起源的。虽然这种疾病可以发生在所有年龄段，但发病率随着年龄的增长而增加，通常在40岁以上的成年人中开始发病。NHL的特征在于淋巴细胞的克隆性增殖，其积聚在淋巴结、血液、骨髓和脾脏中，尽管可以涉及任何主要器官。 NHL可分为两个预后组：惰性和侵袭性。强化联合化疗方案治愈了一些侵袭性NHL病例。影响近一半NHL患者的更惰性和滤泡形式的疾病被认为是不可治愈的。虽然惰性NHL对放疗和化疗有反应，但在晚期通常会出现持续的复发率。对于初次治疗后复发且不适合干细胞移植的患者，需要能够提供临床获益的新疗法。 肿瘤坏死因子（TNF）超家族成员CD 40在侵袭性NHL上的表达使该抗原成为治疗复发患者的有吸引力的靶点。CD 40是所有成熟B细胞（B淋巴细胞）、大多数B细胞恶性肿瘤、单核细胞、树突细胞（神经系统中）、内皮细胞（血管内）和上皮细胞的细胞表面上的受体分子。 终点： 这是一项I期研究，因此终点将包括： + 定义NHL患者接受SGN-40每周4次给药的安全性特征[剂量限制性毒性（DLT）] + 确定NHL患者接受SGN-40每周4次给药的最大耐受剂量（MTD） + 在NHL患者中获得SGN-40的初步抗肿瘤活性