Radioimmunotherapy of Acute Leukemia

急性白血病的放射免疫治疗

• 批准号: 6601561
• 负责人: Eneida R Nemecek
• 金额: $ 13.37万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6601561
• 关键词: Macaca nemestrina; acute leukemia; acute myelogenous leukemia; bone marrow transplantation; clinical research; hematopoietic tissue transplantation; human subject; lymphocytic leukemia; monoclonal antibody; neoplasm /cancer radioimmunotherapy; patient oriented research; radionuclides; radiotracer; stem cell transplantation

DESCRIPTION (provided by applicant): The main objective of this award is to enable the candidate to acquire the skills necessary to become an independent clinical investigator in the field of marrow transplantation for acute leukemia. This research award is intended to evaluate radiolabeled monoclonal antibody therapy as a means to improve the outcome of hematopoietic stem cell transplant (HSCT) for patients with acute myeloid (AML) and lymphoid (ALL) leukemia. Studies of 131I-anti-CD45 antibody combined with conventional HSCT regimens have shown that this antibody can deliver significant targeted radiation to hematopoietic tissues while relatively sparing normal organs. Preliminary results of a study of patients with AML in first remission receiving antibody, busulfan and cyclophosphamide followed by related HSCT are encouraging. In contrast, many patients with advanced AML or ALL receiving radiolabeled antibody, cyclophosphamide and total body irradiation followed by related or unrelated HSCT have relapsed. These preliminary results indicate the need to further define the impact on disease free-survival of a regimen using 131I-anti-CD45 antibody in patients with AML in first remission with an extended Phase II study and a subsequent Phase III study, as proposed in Aim 1. The high relapse rates and transplant-related mortality in patients with advanced acute leukemia suggest the need to find methods to improve targeting of hematopoietic tissues without adding excess toxicity, as proposed in Aim 2. Preliminary pre-clinical studies have suggested that alternative radioisotopes of higher energy and shorter half-life than 131I such as yttrium-90 (90Y) may improve the relative radiation delivered to target hematopoietic tissues. The potential benefit of this isotope can be determined by studying the relative organ localization and retention of 90Y-anti-CD45 antibody in non-human primates, an animal model that has been very predictive of the biodistribution of radiolabeled anti-CD45 antibody in humans. If these pre-clinical studies suggest a potential therapeutic advantage for 90Y, they will provide the background necessary to initiate the evaluation of this approach in a Phase I clinical study, To complement the proposed mentored research activities, the candidate will also participate in a structured didactic program in clinical research and nuclear medicine.

描述（由申请人提供）：该奖项的主要目的是使候选人能够获得成为急性白血病骨髓移植领域的独立临床研究者所必需的技能。 该研究奖旨在评估放射性标记的单克隆抗体疗法，以改善急性髓样（AML）和淋巴样（所有）白血病患者造血干细胞移植（HSCT）的结果。 对131-ANTI-CD45抗体结合使用常规HSCT方案的研究表明，该抗体可以对造血组织提供明显的靶向辐射，同时相对较高的正常器官。 在接受抗体，Busulfan和环磷酰胺随后是相关HSCT的AML患者研究中，AML患者的初步结果令人鼓舞。 相比之下，许多患有晚期AML或所有接受放射标记抗体，环磷酰胺和全身照射的患者，然后是相关或无关的HSCT。 这些初步的结果表明，有必要进一步定义AML患者在AML患者中使用131I-ANTI-CD45抗体对疾病自由活性影响的影响，并在AIM 1中提出了一项延长的II期研究和随后的III期研究，并提出了AIM 1的III期研究。在AIM 2中提出的那样，没有增加过量的毒性。初步临床前研究表明，比Yttrium-90（90Y）等131I（90Y）的替代放射性异位素可以改善传递到靶造血组织的相对辐射。 该同位素的潜在益处可以通过研究非人类灵长类动物中90Y-ANTI-CD45抗体的相对器官定位和保留，这是一种非常预测人类放射性标记抗CD45抗体的生物分布的动物模型。 如果这些临床前研究提出了90年代的潜在治疗优势，则它们将提供必要的背景来在I期临床研究中对该方法进行评估，以补充拟议的指导研究活动，候选人还将参加临床研究和核医学的结构性教学计划。