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

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 假设： 该阶段I研究的目标是非霍奇金淋巴瘤（NHL）的患者： 1。定义每周4剂抗人CD40单克隆抗体的安全概况，SGN-40 2。确定每周4剂量的最大耐受剂量 3。获得SGN-40的初步抗肿瘤活性 目标： NHL是源自淋巴细胞的异质性恶性肿瘤。在美国，估计发病率约为54,000/年，患病率约为331,000。大多数（80％）的淋巴瘤病例是B细胞起源。虽然该疾病在各个年龄段都可以发生，但发病率随着年龄的增长而增加，通常的发作开始于40年以上的成年人。 NHL的特征是淋巴细胞的克隆增殖，这些淋巴细胞积聚在淋巴结，血液，骨髓和脾脏中，尽管可能涉及任何主要器官。 NHL可以分为两个预后组：懒惰和侵略性。强化组合化疗方案可以治愈某些侵略性形式的NHL的情况。影响所有NHL患者几乎一半的疾病的懒惰和卵泡形式被认为是无法治愈的。虽然懒惰的NHL对放射疗法和化学疗法有反应，但通常在晚期阶段可以看到连续的复发率。在从初级治疗中复发并且不是干细胞移植的候选者的患者中，需要提供可以提供临床益处的新型疗法。 CD40的表达是肿瘤坏死因子（TNF）超家族的成员，对侵略性NHL的表达使该抗原成为治疗复发患者的有吸引力的靶标。 CD40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，树突状细胞（在神经系统中），内皮细胞（血管内）和上皮细胞的受体分子。 端点： 这是I阶段研究，因此端点将包括： + NHL患者的40剂量SGN-40的安全概况[剂量限制毒性（DLT）] +确定NHL患者的40例SGN-40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