RADIOIMMUNOTHERAPY OF LYMPHOMA

描述：（改编自申请人摘要）虽然 放射免疫疗法（RIT）似乎有希望作为一种新的治疗方法 淋巴瘤的治疗方式，对肿瘤部位的放射输送不理想， 剂量限制性骨髓抑制仍然是重要的问题。 的 该项目的指导假设是，B细胞淋巴瘤的RIT可以 a）通过使用放射性标记的单克隆抗体 对B细胞的特异性比以前使用的那些更受限制，B） 通过操纵抗体给药方法，和c）通过使用 骨髓辐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 进行一个逐步的，三部分的I期临床试验。 在第一部分中， 不需要骨的131-I-抗B1的最大耐受剂量（MTD） 支持骨髓移植，适合多次给药 时间表将由I期辐射剂量递增确定， 连续几组病人。 作为毒性评估的一部分， 关于外周血和骨髓造血的详细研究 将进行恢复（包括骨髓祖细胞测定）。 此外，在试验的这一部分，肿瘤靶向问题将是 在一项研究中，不同水平的未标记的 抗体预给药对示踪标记抗B1的生物分布的影响将 测定 这些示踪剂研究的结果将应用于 计划在每个患者中随后输送RIT剂量。 在 第二部分，联合IL-1-α的可行性、安全性和毒性 131-I-抗B1将在进入三个 在MTD之前给予连续递增剂量水平的IL-1-α， 第I部分中测定的131-I-抗B1。同样详细的血液学研究 将在这些接受IL-1-α治疗的患者中进行， 可以将它们与第I部分中未给予IL-1-α的患者进行比较。在 第三部分，将确定更高的131-I-抗-B1 MTD是否可以 给予接受过IL-1-alpha预治疗的患者。 将继续进行详细的血液学研究， 比较的目的。

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.