Evaluation of Safety and Efficacy of VELCADE as Maintenance Treatment in Patients With Multiple Myeloma Following High-Dose Melphalan Treatment and Autologous PBSCT (Minimal Residual Disease, Partial Remission or Stable Disease)
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 61
- 试验地点
- 8
- 主要终点
- Primary endpoints are to study the safety of four cycles of VELCADE in patients with multiple myeloma following high-dose chemotherapy and autologous PBSCT.
研究概览
简要总结
Protocol DSMM VIII is a multi-center, open-label study evaluating the safety and tolerability, as well as the efficacy, of maintenance treatment with VELCADE (bortezomib) in patients with multiple myeloma with detectable disease activity following tandem high-dose chemotherapy and autologous SCT. The time from SCT to the initiation of VELCADE treatment will be 3 to 6 months.
详细描述
Protocol DSMM VIII is a multi-center, open-label study evaluating the safety and tolerability, as well as the efficacy, of maintenance treatment with VELCADE in patients with multiple myeloma with detectable disease activity following tandem high-dose chemotherapy and autologous SCT. The time from SCT to the initiation of VELCADE treatment will be 3 to 6 months.
The initial 11 patients entered into this trial will be treated at a dose level of 1.0 mg/m2 once weekly on 4 consecutive weeks followed by 2 weeks of rest. A total of 4 treatment cycles is planned.
An interim analysis for safety and tolerability will be performed after at least the first cycle of study drug has been completed. If the study treatment is found to be safe and no dose-limiting toxicity has occurred, the dose of VELCADE will be increased to 1.3 mg/m2 and another 11 patients will be treated at this dose level according to the treatment schedule as outlined above. The dose escalation to 1.3 mg/m2 will be performed without delay if no AE or SAE are reported to the principal investigator.
If the safety of a specific dose level is acceptable the efficacy of the maintenance treatment will be statistically evaluated. The treatment is considered to be efficacious if a minimum of 25% of all treated patients experience a success, considered as remission of their disease within 6 months after the end of VELCADE treatment. The therapy will be acceptable for further clinical studies if a minium of 25% successfully treated patients will be observed.
Under these assumptions in the first step of the optimal two step design (Simon 1989) 21 patients have to be treated. As patients included during phase I are included in the efficacy analysis, this means an additional 10 patients to be treated. If less than three patients were successfully treated defined as an improvement in the remission status, the study will be stopped, because the success rate is unacceptably low. If three or more of the 21 patients are successfully treated, another 29 patients will be included. At the end of the study the success rate will be evaluated. If 8 or more of the 50 patients were successfully treated the therapy will be acceptable for further studies.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient having received tandem transplants with high-dose melphalan and autologous PBSCT within 3-6 months prior to inclusion into this protocol
- •Patients with measurable minimal residual disease (very good partial remission [VGPR]) or patients in partial remission (PR) or patients with stable disease (SD) at the time of inclusion in the study
- •Patient must agree to participate in the study.
- •Patient agrees to use an appropriate method of contraception.
- •Willingness and ability to comply with the study protocol for the duration of the study
排除标准
- •Patient showing signs of disease progression
- •Patient has a platelet count < 100 x 10^9/L within 14 days before enrollment.
- •Patient has an absolute neutrophil count < 1.0 x 10^9/L within 14 days before enrollment.
- •Patient has a calculated or measured creatinine clearance < 30 mL/minute within 14 days before enrollment.
- •Patient has >= Grade 2 peripheral neuropathy within 14 days before enrollment.
- •Patient has hypersensitivity to bortezomib, boron, or mannitol.
- •Patient has received prior treatment with bortezomib
- •Patient is pregnant or nursing
- •Patient has received other investigational drugs within 14 days before enrollment
- •Patient has progressive disease
- •Patient has a Karnofsky performance status < 60%
- •Patient has a life expectancy of < 3 months
- •Patient has received disease modifying agents following autologous stem cell transplantation other than aminobisphosphonates such as interferon-alpha or glucocorticosteroids
- •Patient currently enrolled in another clinical research study and/or receiving an investigational reagent for any reason.
结局指标
主要结局
Primary endpoints are to study the safety of four cycles of VELCADE in patients with multiple myeloma following high-dose chemotherapy and autologous PBSCT.
次要结局
- The secondary objectives of this study are to assess the efficacy of four cycles of VELCADE at two different dose levels as maintenance treatment in patients with multiple myeloma
- and detectable residual disease following high-dose chemotherapy and autologous PBSCT
- to assess the 2 year progression-free survival
- and to assess the 2 year overall survival.