Radioimmunotherapy Based Transplant Regimens for Treatment of B-Cell Lymphoma and

基于放射免疫疗法的 B 细胞淋巴瘤和移植治疗方案

• 批准号: 7016807
• 负责人: Stephen J Forman
• 金额: $ 59.21万
• 依托单位: BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7016807
• 关键词: B cell lymphoma; acute myelogenous leukemia; antiantibody; clinical research; clinical trial phase I; clinical trial phase II; hematopoietic tissue transplantation; homologous transplantation; human subject; human therapy evaluation; neoplasm /cancer radioimmunotherapy; neoplasm /cancer transplantation; patient oriented research; radiotracer; relapse /recurrence; tumor antigens; yttrium

Relapse remains the most important cause of failure for many patients undergoing either autologous or allogeneic transplant for the treatment of malignant lymphoma and acute myelogenous leukemia. This project will focus on studies of radioimmunotherapy targeted to tumor-associated antigens, as a component of the preparatory regimens for autologous and allogeneic hematopoietic cell transplantation used in the treatment of these diseases. The proposed studies seek to improve the anti-tumor efficacy, as well as reduce the toxicity of the procedure which will extend the application of hematopoietic cell transplantation (HCT) to older patients who form the majority of patients with both AML and lymphoma. The proposed studies will investigate the incorporation of radiolabeled antibodies conjugated to a heavy metal radioisotope (Yttrium-90) that target either the CD20 antigen on malignant B-cells or the CD33 antigen on blasts in patients with AML and myelodysplasia. We propose to perform five clinical studies using novel regimens for autologous or allogeneic transplant for AML and B-cell lymphoma: 1) For patients with advanced lymphoma (low-grade, intermediate-grade, and mantle cell) we will continue our studies of high-dose 90Y-labeled anti-CD20 antibody combined with etoposide and cyclophosphamide in the Phase II setting; 2) For older patients (age>60) with relapsed lymphoma we will extend our Phase I observations to a Phase II study of 90Y-labeled anti-CD20 antibody combined with BEAM chemotherapy in order to develop an effective regimen that can be used safely in this population of patients; 3) 90Y-labeled anti-CD20 antibody will also be developed as part of a reduced intensity allogeneic transplant regimen for patients with lymphoma who are not candidates for an autologous approach, including those with relapsed mantle cell lymphoma, multiple relapsed low-grade lymphoma, or patients who have relapsed after autologous transplant; 4) For patients with AML, who have intermediate- and high-risk cytogenetics, we will initiate a study of 90Y-labeled anti-CD33 antibody to replace total body irradiation in combination with etoposide and cyclophosphamide for autologous transplant; 5) After completion of a Phase I safety study, we will conduct a Phase II study with this regimen. For patients with advanced leukemia (early relapse, older age, AML with prior MDS, relapse after auto-transplant), we will incorporate the 90Y-labeled anti-CD33 antibody into a reduced intensity allogeneic transplant regimen to improve the outcome for this high-risk population of patients. It is the general hypothesis of this project that targeted radiation therapy as a component of the autologous and allogeneic transplant preparative regimens will help improve therapeutic efficacy by decreasing post-HCT disease relapse and by reducing toxicity, thereby extending the potential benefit of treatment to a larger population of patients with these diseases.

对于许多接受自体或异体移植的患者来说，复发仍然是失败的最重要原因 移植治疗恶性淋巴瘤和急性髓性白血病。该项目将重点研究 针对肿瘤相关抗原的放射免疫治疗，作为治疗准备方案的一部分 自体和异体造血细胞移植用于治疗这些疾病。拟议的 研究旨在提高抗肿瘤功效，并降低手术的毒性，从而延长治疗时间 造血细胞移植（HCT）在老年患者中的应用，这些患者占大多数患有两种 AML 的患者 和淋巴瘤。拟议的研究将调查与结合的放射性标记抗体的结合 重金属放射性同位素 (Yttrium-90)，靶向恶性 B 细胞上的 CD20 抗原或恶性 B 细胞上的 CD33 抗原 AML 和骨髓增生异常患者的原始细胞。我们建议使用新疗法进行五项临床研究 用于治疗 AML 和 B 细胞淋巴瘤的自体或同种异体移植： 1) 对于晚期淋巴瘤患者（低级别、 中级和套细胞）我们将继续研究高剂量90Y标记的抗CD20抗体组合 II 期试验中使用依托泊苷和环磷酰胺； 2) 对于患有复发性淋巴瘤的老年患者（年龄>60） 我们将把我们的 I 期观察扩展到 90Y 标记的抗 CD20 抗体与 BEAM 结合的 II 期研究 化疗以开发可安全用于该患者群体的有效治疗方案； 3) 还将开发 90Y 标记的抗 CD20 抗体，作为降低强度同种异体移植方案的一部分，适用于不适合自体方法的淋巴瘤患者，包括复发性套细胞淋巴瘤、多发性复发低度淋巴瘤、或自体移植后复发的患者； 4）对于细胞遗传学中高危的AML患者，我们将启动90Y标记抗CD33抗体替代全身照射联合依托泊苷和环磷酰胺进行自体治疗的研究 移植; 5）完成I期安全性研究后，我们将对该方案进行II期研究。为了 晚期白血病患者（早期复发、年龄较大、患有既往 MDS 的 AML、自体移植后复发），我们将 将 90Y 标记的抗 CD33 抗体纳入强度降低的同种异体移植方案中，以改善 这一高危患者群体的结果。该项目的一般假设是针对辐射 作为自体和异体移植准备方案的一部分的治疗将有助于改善治疗 通过减少 HCT 后疾病复发和降低毒性来提高疗效，从而扩大潜在益处 为更多患有这些疾病的患者提供治疗。