A Phase I-II Study of the Combination of Bendamustine and Pomalidomide With Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 56
- 试验地点
- 1
- 主要终点
- Initial Response Rate
研究概览
简要总结
This study is designed as a phase I-II, open label, dose finding study.
Study treatment will be as follows, in 28 day cycles:
- Pomalidomide: once daily orally (PO) dosing on days 1-21, every 28 days
- Bendamustine: once intravenously (IV) dosing on day 1, every 28 days
- Dexamethasone: weekly PO or IV dosing on days 1, 8, 15, and 22.
After completing 6 cycles of treatment, dexamethasone may be decreased to 20mg per investigator discretion. After completing 12 cycles of treatment, patients will proceed to the maintenance phase of the study. Patients will receive Pomalidomide on day 1-21, every 28 days and dexamethasone on days 1, 8, 15, and 22 every 28 days until time of progression.
详细描述
PRIMARY ENDPOINTS:
Phase I • Determination of the MTD of the combination therapy
Phase II:
• Response rate (CR+PR)
SECONDARY ENDPOINTS:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
Cohort 1: benda 120mg + pom 3mg
- Pomalidomide: once daily oral (PO) dosing on days 1-21, every 28 days
- Bendamustine: once intravenous (IV) dosing on day 1, every 28 days
- Dexamethasone: weekly PO or IV dosing on days 1, 8, 15, and 22 every 28 days
干预措施: Bendamustine (Drug)
Cohort 1: benda 120mg + pom 3mg
- Pomalidomide: once daily oral (PO) dosing on days 1-21, every 28 days
- Bendamustine: once intravenous (IV) dosing on day 1, every 28 days
- Dexamethasone: weekly PO or IV dosing on days 1, 8, 15, and 22 every 28 days
干预措施: Pomalidomide (Drug)
Cohort 1: benda 120mg + pom 3mg
- Pomalidomide: once daily oral (PO) dosing on days 1-21, every 28 days
- Bendamustine: once intravenous (IV) dosing on day 1, every 28 days
- Dexamethasone: weekly PO or IV dosing on days 1, 8, 15, and 22 every 28 days
干预措施: Dexamethasone (Drug)
Cohort 2: benda 120mg + pom 4mg
- Pomalidomide: once daily oral (PO) dosing on days 1-21, every 28 days
- Bendamustine: once intravenous (IV) dosing on day 1, every 28 days
- Dexamethasone: weekly PO or IV dosing on days 1, 8, 15, and 22 every 28 days
干预措施: Bendamustine (Drug)
Cohort 2: benda 120mg + pom 4mg
- Pomalidomide: once daily oral (PO) dosing on days 1-21, every 28 days
- Bendamustine: once intravenous (IV) dosing on day 1, every 28 days
- Dexamethasone: weekly PO or IV dosing on days 1, 8, 15, and 22 every 28 days
干预措施: Pomalidomide (Drug)
Cohort 2: benda 120mg + pom 4mg
- Pomalidomide: once daily oral (PO) dosing on days 1-21, every 28 days
- Bendamustine: once intravenous (IV) dosing on day 1, every 28 days
- Dexamethasone: weekly PO or IV dosing on days 1, 8, 15, and 22 every 28 days
干预措施: Dexamethasone (Drug)
Expansion
- Pomalidomide 3mg: once daily oral (PO) dosing on days 1-21, every 28 days
- Bendamustine 120 mg: once intravenous (IV) dosing on day 1, every 28 days
- Dexamethasone: weekly PO or IV dosing on days 1, 8, 15, and 22 every 28 days
干预措施: Bendamustine (Drug)
Expansion
- Pomalidomide 3mg: once daily oral (PO) dosing on days 1-21, every 28 days
- Bendamustine 120 mg: once intravenous (IV) dosing on day 1, every 28 days
- Dexamethasone: weekly PO or IV dosing on days 1, 8, 15, and 22 every 28 days
干预措施: Pomalidomide (Drug)
Expansion
- Pomalidomide 3mg: once daily oral (PO) dosing on days 1-21, every 28 days
- Bendamustine 120 mg: once intravenous (IV) dosing on day 1, every 28 days
- Dexamethasone: weekly PO or IV dosing on days 1, 8, 15, and 22 every 28 days
干预措施: Dexamethasone (Drug)
结局指标
主要结局
Initial Response Rate
时间窗: 2 cycles (approximately 2 months)
The number of patients achieving a complete response (CR) or partial response (PR). Response is defined by the International Myeloma Working Group as: CR- Negative immunofixation on serum and urine and disappearance of soft tissue plasmacytomas and \< 5% plasma cells in bone marrow PR- \> 50% reduction of serum M-protein and urine M-protein by \>90% or to \< 200 mg/24 h In addition, if present at baseline, a \> 50% reduction in the size of soft tissue plasmacytomas is also required VGPR - Serum and urine M-protein detectable by immunofixation but n
Maximum Tolerated Dose of Pomalidomide and Bendamustine
时间窗: 2 cycles (approximately 2 months)
In the phase I dose escalation portion, patients will be sequentially enrolled in 4 cohorts at dose levels in a standard 3+3 design until the maximum tolerated dose (MTD) is reached. Cohort 1 (bendamustine 120mg/m2 + pomalidomide 3mg); Cohort 2 (bendamustine 120mg/m2 + pomalidomide 4mg); Cohort 3 (bendamustine 150mg/m2 + pomalidomide 4mg); Cohort 4 (bendamustine 180mg/m2 + pomalidomide 4mg) If dose limiting toxicity (DLT) is observed in 2 or more of the six patients at the same dosing level while DLT is observed in only 1 or none of the 6 patients at the dosing level immediately below it, then the lower dosing level will be defined as the maximum tolerated dose (MTD).
次要结局
- Time to Next Therapy(2 years after last dose of study drug)
- Time to Progression(2 years after last dose of study drug)
- Overall Response Rate(2 years after last dose of study drug)
- Progression Free Survival(2 years after last dose of study drug)
研究者
Cristina Gasparetto
Sponsor Investigator
Duke University