A Phase II Study of Perifosine in Patients With Relapsed/Refractory Waldenstrom's Macroglobulinemia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 37
- 试验地点
- 1
- 主要终点
- Overall Response (OR) Rate
研究概览
简要总结
Waldenström's Macroglobulinemia (lymphoplasmacytic lymphoma, WM) remains incurable with limited therapeutic options and notably absent FDA approved therapy with any WM indication. Therefore, there is a need to identify new therapeutic agents for WM patients both in the upfront and relapsed/refractory setting. The purpose of this research study is to assess the efficacy of perifosine in patients with relapsed or refractory WM.
详细描述
Perifosine is a drug that in particular inhibits Akt thought to be important for initiation and progression of malignancies, specifically in lymphomas. In laboratory experiments of WM and lymphoma cell lines, perifosine has shown to have cytotoxic and anti-proliferative activity as a single agent. This drug has been used in clinical research studies of other types of cancers including soft tissue sarcomas, head and neck cancers and prostate cancer. This study uses a two-stage design to evaluate efficacy of perifosine based on overall response (OR). The null and alternative OR rates are 20% and 40%. If 4 or more patients enrolled in the stage one cohort (n=17 patients) achieve OR than accrual will proceed to stage two (n=20 patients). If fewer than 10 ORs are observed then the regimen will be considered ineffective.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •18 years of age or older
- •Must have received prior therapy for their WM and have relapsed or refractory WM. Any number of prior therapies is acceptable
- •Measurable disease, defined as presence of immunoglobulin M paraprotein with a minimum IgM level of equal to or greater than 2 times the ULN and over 10% of lymphoplasmacytic cells in bone marrow
- •ECOG Performance Status 0,1, or 2
- •Laboratory values as described in the protocol
- •Life expectancy of greater than 12 weeks
排除标准
- •Uncontrolled infection
- •Other active malignancies
- •CNS involvement
- •Cytotoxic chemotherapy less than 3 weeks, or biologic therapy less than 2 weeks, or corticosteroids less than 2 weeks prior to registration.
- •Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational
- •Pregnant or nursing women
- •Known to be HIV positive
- •Radiation therapy less than 2 weeks prior to registration
研究组 & 干预措施
Perifosine
Patients receive oral perifosine (150 mg) daily each cycle. Cycle duration is 28 days. After cycle 2, response is assessed and patients with stable or responding disease can continue for another 4 cycles or until disease progression (PD). Protocol treatment duration is 6 cycles but patients may receive perifosine maintenance per investigator discretion in absence of PD.
干预措施: Perifosine (Drug)
结局指标
主要结局
Overall Response (OR) Rate
时间窗: Disease was assessed every cycle for the first 12 months and every 3 months thereafter. The median duration of treatment with perifosine was 5.6 months (range, 1.8- 21.5+).
OR rate is the percentage of patients achieving Complete Response (CR), Partial Response (PR) or Minimal Response (MR) during treatment based on criteria from the 2nd International Workshop on WM. (Weber D, Treon S, et al. Seminars in Oncology 2003). CR: Disappearance of serum monoclonal IgM protein (IgM M-protein) by immunofixation; no histologic evidence of bone marrow (BM) involvement, resolution of any adenopathy/organomegaly (confirmed by CT scan); PR: At least 50% reduction of IgM M-protein and at least 50% decrease in adenopathy/organomegaly on physical examination or on CT scan; and MR: At least 25% but less than 50% reduction of IgM M-protein by protein electrophoresis. Patients must have no new symptoms or signs of active disease.
次要结局
- Time to Progression (TTP)(Disease was assessed every cycle for the first 12 months and every 3 months thereafter. Median follow-up time was 19.5 months and range up to 24 months.)
- Progression Free Survival (PFS)(Disease was assessed every cycle for the first 12 months and every 3 months thereafter. Median follow-up time was 19.5 months and range up to 24 months.)
- Treatment-Related Grade 3-4 Adverse Event Rate(Adverse events were collected every cycle on treatment.The median treatment duration was 5.6 months (range, 1.8-21.5+).)
研究者
Irene Ghobrial, MD
Principal Investigator
Dana-Farber Cancer Institute