STRATEGIES FOR CURE IN NEWLY DIAGNOSED MULTIPLE MYELOMA

新诊断的多发性骨髓瘤的治疗策略

• 批准号: 6594580
• 负责人: BART BARLOGIE
• 金额: $ 27.95万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-06-01 至 2003-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6594580
• 关键词: angiogenesis inhibitors; autologous transplantation; chromosome deletion; cis platinum compound; clinical research; cyclophosphamide; dexamethasone; drug administration rate /duration; drug resistance; etoposide; fluorescent in situ hybridization; human subject; human therapy evaluation; long term survivor; magnetic resonance imaging; metastasis; multiple myeloma; neoplasm /cancer chemotherapy; neoplasm /cancer classification /staging; neoplasm /cancer genetics; neoplasm /cancer relapse /recurrence; neoplasm /cancer remission /regression; outcomes research; thalidomide

DESCRIPTION: (Applicant's Description) Project 1 will explore novel therapeutic strategies for newly diagnosed MM patients in an effort to improve upon clinical results obtained with the "Total Therapy Program," developed and instituted during the past funding period. Total Therapy, which comprises multi-regimen induction and myeloablative therapy in the tandem transplant setting, has allowed advances in myeloma therapy to be made at last, achieving CRs in 40-50 percent of patients, which lasted a median of 50 months. The goal of future therapies must be to further enhance the incidence and duration of CR, which is the focus of Project 1. We will develop and test new treatment strategies based on our long-standing hypothesis that therapies that increase the incidence of CR are key to eliciting longer event-free survival and overall survival in newly diagnosed myeloma patients. Four specific aims will address two problem areas: being able to achieve a high incidence of sustained CR and identifying obstacles to sustaining CR (genetically defined resistance, tumor burden). SA1: Evaluate, in a randomized phase III clinical trial, whether the addition of the anti-angiogenesis compound, thalidomide, to the total therapy regimen can improve CR rate and extend CR duration as well as event-free and overall survival in newly diagnosed patients. SA2: Determine, in a randomized trial, whether further intensification of consolidation therapy after tandem autotransplants can increase CR rate and prevent disease recurrence. SA3: Prospectively dissect the genetic heterogeneity of myeloma by performing metaphase and interphase FISH karyotyping at defined intervals during therapeutic intervention in the context of clinical outcome related to the 2 therapeutic trial questions posed in Aims 1 & 2. SA4: Evaluate, systematically and in a prospective fashion, the usefulness of serial magnetic resonance (MR) imaging analysis of axial marrow to document the pattern and extent of marrow involvement (tumor burden) and changes during therapy ("MR-CR") as they relate to outcome. These studies are a logical extension of the findings obtained during the previous funding period and, in concert with research conducted in 5 other projects and with access to 3 cores, will provide currently unavailable insights into myeloma biology and staging.

描述：（申请人的描述）项目1将探索小说 新诊断的MM患者的治疗策略以改善 根据“全面治疗计划”获得的临床结果，开发了 在过去的资金期间建立。总疗法，包括 串联移植中的多限制诱导和髓裂疗法 设置，终于可以做出骨髓瘤疗法的进步 40-50％的患者中位数为50个月的患者中的CR。这 未来疗法的目标必须是进一步提高发病率和持续时间 CR，这是项目1的重点。我们将开发和测试新 基于我们长期存在的假设的治疗策略 增加CR的发生率是引发更长的无事件生存的关键 以及新诊断的骨髓瘤患者的总体生存。四个具体目标 将解决两个问题领域：能够达到高的发生率 持续的CR并确定维持CR的障碍（遗传定义 阻力，肿瘤负担）。 SA1：在随机的III期临床中评估 试验，是否添加抗血管生成化合物，沙利度胺， 总治疗方案可以提高CR率并延长CR持续时间 作为新诊断的患者的无事件和整体生存。 SA2： 在随机试验中确定是否进一步加强 串联自动载体后的合并疗法可以提高CR率和 预防疾病复发。 SA3：前瞻性剖析 通过执行中期和相间鱼的骨髓瘤异质性 在治疗干预期间，按定义间隔进行核分型 与提出的2个治疗试验问题有关的临床结果背景 在目标1＆2。SA4中：系统地进行评估，以一种潜在的方式进行评估 轴向串行磁共振（MR）成像分析的有用性 记录骨髓参与的模式和程度（肿瘤负担） 与结果相关的治疗过程中的变化（“ MR-CR”）。这些研究 是以前资金中获得的发现的逻辑扩展 时期，并与其他5个项目一起进行研究 使用3个核心，将提供当前无法获得骨髓瘤的见解 生物学和分期。