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 将探索新颖的 新诊断 MM 患者的治疗策略，努力改善 根据“全面治疗计划”获得的临床结果，制定并 在过去的资助期内设立。全面治疗，包括 串联移植中的多方案诱导和清髓治疗 背景下，终于使骨髓瘤治疗取得了进展，实现了 40-50% 的患者获得 CR，中位持续时间为 50 个月。这 未来治疗的目标必须是进一步提高发病率和持续时间 CR的，这是项目1的重点。我们将开发和测试新的 治疗策略基于我们长期以来的假设，即治疗 增加 CR 发生率是延长无事件生存期的关键 以及新诊断的骨髓瘤患者的总生存率。四个具体目标 将解决两个问题领域：能够实现高发生率 持续 CR 并识别维持 CR 的障碍（基因定义 抵抗力、肿瘤负荷）。 SA1：在随机 III 期临床中进行评估 试验，是否添加抗血管生成化合物沙利度胺 整体治疗方案可提高CR率并延长CR持续时间 新诊断患者的无事件生存率和总生存率。 SA2： 在随机试验中确定是否进一步强化 串联自体移植后的巩固治疗可提高 CR 率 防止疾病复发。 SA3：前瞻性剖析遗传 通过中期和间期 FISH 观察骨髓瘤的异质性 在治疗干预期间按规定的时间间隔进行核型分析 与提出的 2 个治疗试验问题相关的临床结果背景 目标 1 和 2。 SA4：系统地、前瞻性地评估， 轴向序列磁共振 (MR) 成像分析的有用性 骨髓记录骨髓受累的模式和程度（肿瘤负荷） 以及治疗期间与结果相关的变化（“MR-CR”）。这些研究 是先前资助期间获得的研究结果的逻辑延伸 期间，并与其他 5 个项目中进行的研究相结合 访问 3 个核心，将提供目前无法获得的骨髓瘤见解 生物学和分期。