BRYOSTATIN 1 THERAPY FOLLOWED BY VAD FOR MULTIPLE MYELOMA

苔藓抑素 1 疗法继之以 VAD 治疗多发性骨髓瘤

• 批准号: 6264075
• 负责人: DEBORAH C MARCELLUS
• 金额: $ 0.23万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6264075
• 关键词: antineoplastics; bryostatin; clinical research; combination chemotherapy; cyclin dependent kinase; cytokine; dexamethasone; doxorubicin; drug administration rate /duration; drug screening /evaluation; human subject; human therapy evaluation; injection /infusion; interleukin 6; multiple myeloma; neoplasm /cancer chemotherapy; vincristine

This study involves a randomized Phase II, window of opportunity study of Bryostatin 1 followed by treatment with VAD 9Vincristine, Adriamycin and Decadron) in previously untreated patients with multiple myeloma. The primary objectives are: 1. To seek preliminary evidence of therapeutic activity of Bryostatin 1 when administered as a continuous IV infusion, either over 72 hours every two weeks or for 24 hours every week in patients with multiple myeloma. 2. To describe and quantitate the toxicity of Bryostatin 1 administered intravenously as a continuous infusion, either over 72 hours every two weeks or for 24 hours every week in patients with multiple myeloma. The secondary objects are: 1. To obtain preliminary data regarding the effect and toxicity of VAD when administered after Bryostatin 1. 2. to assess steady state concentrations of Bryostatin 1 during course one of therapy, using a bioassay. 3. To evaluate T lymphocyte subsets before and during Bryostatin 1 infusions. 4. To measure serum interleukin-6 (IL-6) levels pre and post administration of Bryostatin 1 during the first cycle. 5. Attempt to isolate malignant plasma cells from the bone marrow of patients, before treatment, to evaluate the effect of Bryostatin 1 on myeloma cell viability, cyclin-dependent kinase 2 expression and activation, and cytokine production.

该研究涉及一项随机II期机会窗口研究，在先前未治疗的多发性骨髓瘤患者中，Bryostatin 1随后使用VAD（长春新碱、阿霉素和decdecadron）治疗。主要目标是：1。在多发性骨髓瘤患者中，连续静脉输注苔藓抑素1 (Bryostatin 1)，每两周超过72小时或每周24小时，寻求其治疗活性的初步证据。2. 描述和量化多发性骨髓瘤患者静脉连续输注苔藓虫素1的毒性，每两周超过72小时或每周24小时。从对象有：1；获得关于苔藓虫素1后使用VAD的效果和毒性的初步数据。2. 使用生物测定法评估治疗过程中苔藓虫素1的稳态浓度。3. 观察苔藓虫素1输注前后T淋巴细胞亚群的变化。4. 测定第一个周期给药苔藓虫素1前后血清白介素-6 （IL-6）水平。5. 尝试在治疗前从患者骨髓中分离恶性浆细胞，以评估苔藓虫素1对骨髓瘤细胞活力、细胞周期蛋白依赖性激酶2的表达和激活以及细胞因子产生的影响。