RADIOIMMUNOTHERAPY OF LYMPHOMA

描述：(改编自申请人的摘要) 放射免疫疗法(RIT)似乎有希望成为一种新的治疗方法 淋巴瘤的治疗方式，肿瘤部位的次佳放射治疗和 剂量限制的骨髓抑制仍然是一个重要的问题。这个 该项目的指导性假设是B细胞淋巴瘤的RIT可以是 通过使用放射性标记的单抗进一步增强a) 与以前使用的相比，对B细胞的特异性更有限，b) 通过操纵抗体的给药方法，以及c)通过使用 一种骨髓放射防护细胞因子，如白细胞介素1-α (IL-1-α)。为了研究这些相互关联的问题，申请人将 进行一项分阶段、分三阶段的临床试验。在第一部分中， 不需要骨骼的131-I-抗-B1的最大耐受量(MTD) 支持骨髓移植，适合多次给药 时间表将根据#年第一阶段辐射剂量递增确定 连续的几组病人。作为毒性评估的一部分， 关于外周血和骨髓造血功能的详细研究 将进行恢复(包括骨髓祖细胞分析)。 此外，在试验的这一部分，肿瘤靶向的问题将是 在一项研究中提出了不同水平的未标记的影响 抗体预给药对微量标记抗-B1生物分布的影响 下定决心。这些示踪剂研究的结果将应用于 计划每个患者随后的RIT剂量。在……里面 第二部分，联合应用IL-1-α的可行性、安全性和毒性 用~(131)I-抗-B1将患者测定上三次 持续递增的IL-1-α剂量水平在MTD前给予 第I部分测定的131-I-抗-B1同样详细的血液学检查 将在接受IL-1-α的患者中执行，以便 他们可以与第一部分中未接受IL-1-α治疗的患者进行比较。 第三部分，将确定较高的131-I-抗-B1的MTD是否可以 适用于接受IL-1-α预治疗的患者。 将继续进行详细的血液学研究，以便进一步 比较目的。

DESCRIPTION: (Adapted from applicant's abstract) Although radioimmunotherapy (RIT)appears to have promise as a new therapeutic modality for lymphoma, suboptimal delivery of radiation to tumor sites and dose-limiting myelosuppression remain as significant problems. The guiding hypothesis of this project is that RIT of B-cell lymphoma can be further enhanced a) through the use of radiolabeled monoclonal antibodies with more restricted specificity for Bcells than those previously used, b) through the manipulation of antibodydosing methods, and c) through the use of a bone marrow radioprotective cytokine such as interleukin-1-alpha (IL-1-alpha). To study theseinterrelated issues the applicant will perform a stepwise, three-part phaseI clinical trial. In Part I, the maximum tolerated dose (MTD) of 131-I-anti-B1 which does not require bone marrow transplantation support and is suitablefor a multiple dosing schedule will be determined by phase I radiation dose-escalation in successive groups of patients. As part of the assessment of toxicity, detailed studies regarding peripheral blood and bone marrow hematopoetic recovery (including bone marrow progenitor assays) will be performed. Also, in this part of the trial the issue of tumor targeting will be addressed in a study in which the effects of varying levels of unlabeled antibody predosing on the biodistribution of trace-labeled anti-B1 will be determined. The results from these tracer studies will be applied to the planningof the subsequent delivery of an RIT dose in each patient. In Part II, the feasibility, safety, and toxicity of combining IL-1-alpha with 131-I-anti-B1 will be determined in patients entered onto three successive escalating dose levels of IL-1-alpha given before the MTD of 131-I-anti-B1 determined in Part I. The same detailed hematologic studies will be performed in thesepatients who have received IL-1-alpha so that they may be compared to the patients not given IL-1-alpha in Part I. In part III, it will be determined whether a higher MTD of 131-I-anti-B1 can be given to patients who have received a pretreatment with IL-1-alpha. Detailed hematologic studies will continue to be performed for further comparative purposes.