A Phase I/II Trial of Cyclophosphamide, Carfilzomib, Thalidomide and Dexamethasone (CYCLONE) in Patients With Newly Diagnosed Active Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Mayo Clinic
- 入组人数
- 64
- 试验地点
- 3
- 主要终点
- Maximum Tolerated Dose (Phase I)
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Thalidomide may stop the growth of cancer cells by blocking blood flow to the tumor. Giving combination chemotherapy together with carfilzomib and thalidomide may kill more cancer cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of carfilzomib when given together with cyclophosphamide, thalidomide, and dexamethasone in treating patients with newly diagnosed active multiple myeloma.
详细描述
PRIMARY OBJECTIVES:
I. To establish the maximum tolerated dose of carfilzomib given in combination with oral cyclophosphamide and thalidomide and dexamethasone. (Phase I) II. In newly diagnosed myeloma to evaluate the response rate (CR, nCR, and VGPR) to carfilzomib given in combination with oral cyclophosphamide and thalidomide and dexamethasone after four 28 day cycles. (Phase II)
SECONDARY OBJECTIVES:
I. Determine the overall response rate (CR, nCR, PR) after 4, 8, 12 cycles. II. Determine the duration of progression-free and overall survival for patients receiving this regimen.
III. To evaluate the incidence of toxicities for this regimen. IV. To evaluate the ability to successfully collect peripheral blood stem cells following four months of combination therapy.
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Arm I
Patients receive carfilzomib IV on days 1, 2, 8, 9, 15, and 16; oral cyclophosphamide on days 1, 8, and 15; oral dexamethasone on days 1, 8, 15, and 22; and oral thalidomide on days 1-28.
干预措施: carfilzomib (Drug)
Arm I
Patients receive carfilzomib IV on days 1, 2, 8, 9, 15, and 16; oral cyclophosphamide on days 1, 8, and 15; oral dexamethasone on days 1, 8, 15, and 22; and oral thalidomide on days 1-28.
干预措施: cyclophosphamide (Drug)
Arm I
Patients receive carfilzomib IV on days 1, 2, 8, 9, 15, and 16; oral cyclophosphamide on days 1, 8, and 15; oral dexamethasone on days 1, 8, 15, and 22; and oral thalidomide on days 1-28.
干预措施: thalidomide (Drug)
Arm I
Patients receive carfilzomib IV on days 1, 2, 8, 9, 15, and 16; oral cyclophosphamide on days 1, 8, and 15; oral dexamethasone on days 1, 8, 15, and 22; and oral thalidomide on days 1-28.
干预措施: dexamethasone (Drug)
结局指标
主要结局
Maximum Tolerated Dose (Phase I)
时间窗: From baseline to end of active treatment, up to 12 28-day cycles.
To establish the maximum tolerated dose of carfilzomib given in combination with oral cyclophosphamide and thalidomide and dexamethasone. For this protocol, dose-limiting toxicity (DLT) will be defined as an adverse event attributed (definitely, probably, possibly) in the first or second cycle for patients enrolled to Dose Levels -1 and 0 and in the first cycle only for patients enrolled to Dose Levels 1 and 2. We are reporting the number of DLTs
Percentage of Patients Who Have at Least a Confirmed Very Good Partial Response (Phase II)
时间窗: Following the first 4 cycles of treatment (28 day cycles)
The proportion of patients who have at least a confirmed very good partial response will be calculated by taking the number of patients with a very good partial response or a complete response divided by the total number of patients. A complete response is defined as: * Negative immunofixation of the serum and urine * If at on study, only the measurable non-bone marrow parameter was FLC, normalization of FLC ratio * \< 5% plasma cells in bone marrow * Disappearance of any soft tissue plasmacytomas A very good partial response is defined as: * Serum and urine M-component detectable by immunofixation but not on electrophoresis or * If at on study, serum measurable, ≥ 90% or greater reduction in serum Mcomponent * Urine M-component \<100 mg per 24 hour
次要结局
- Progression-free Survival (Phase II)(From baseline to progression or death up to 3 years)
- Time to Treatment Failure(From baseline to end of active treatment)
- Stem Cell Collection and Engraftment (Phase II)(Following the first 4 courses of treatment)
- Complete Response (Phase II)(Following the first 4 courses of treatment)
- Survival Time (Phase II)(From baseline to death)
- Progression Free Survival (12 Month)(12 months)
- Progession Free Survival (24 Month)(24 months)
- Overall Survival (12 Month)(From baseline to death)
- Overall Survival (24 Month)(From baseline to death)