BRYOSTATIN 1 THERAPY FOLLOWED BY VAD FOR MULTIPLE MYELOMA

这项研究涉及一项随机的第二阶段，即Bryostatin 1的机会窗研究，然后用VAD 9长春新碱、阿霉素和Decadron治疗先前未治疗的多发性骨髓瘤患者。主要目标是：1.寻找Bryostatin 1作为连续静脉输注的治疗活性的初步证据，在多发性骨髓瘤患者中，每两周超过72小时或每周24小时。2.对多发性骨髓瘤患者持续静脉滴注Bryostatin 1每2周72小时以上或每周24小时以上的毒性进行描述和量化。次要目的是：1.获得有关在Bryostatin 1之后使用VAD的疗效和毒性的初步数据。2.使用生物测定法，评估Bryostatin 1在治疗过程中的稳态浓度。3.检测输注Bryostatin 1前后T淋巴细胞亚群的变化。4.测定第一周期应用Bryostatin 1前后血清IL-6水平。5.从患者骨髓中分离恶性浆细胞，在治疗前观察Bryostatin 1对骨髓瘤细胞活力、细胞周期蛋白依赖性激酶2表达和激活以及细胞因子产生的影响。

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.