Randomized, Multicenter Study of Tolerability and Efficacy of Modified Combinations of Bortezomib, Dexamethasone and Cyclophosphamide in Previously Untreated Multiple Myeloma.
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 94
- 试验地点
- 1
- 主要终点
- the rate of complete remission
研究概览
简要总结
This phase 2 study will be conducted at 10 centers and enroll patients from August 2013 to August 2017.Firstly, All patients included will provide written informed consent. Secondly, they will be randomized equally to receive modified VCD regimen arm 1 or modified VCD regimen arm 2. In total, 47 patients per arm (or 94 in total) are required. The treatment consists of four 4-week cycles of induction therapy followed by intensive therapy with another five modified VCD regimens and maintenance treatment with CP regimen. Then, patients will be followed up for 24 months after chemotherapy. The investigators will record all the laboratory and clinical investigations to assess response at different points of the study. We also monitor and assess adverse events (AEs), as graded according to NCI-CTCAE Version 3.0.Response categories were based on the International Myeloma Working Group uniform response criteria.In addition, 20 patients (10 in VCD regimen arm 1 group, 10 in VCD regimen arm 2 group) from ten centres will be enrolled in the pharmacodynamic substudy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Patients with previously untreated symptomatic MM
- •18 years of age or older, regardless of gender
- •secretory MM with measurable diseases
- •Karnofsky Performance Status≥50%（pathological fractures excluded）
- •Patients without heart and pulmonary dysfunction ≤class I
排除标准
- •peripheral neuropathy of grade 2 or higher according to NCI-CTCAE Version 3.0
- •Relapse and refractory MM
- •MM without symptom
- •Non-secretory MM without measurable diseases
- •Karnofsky Performance Status<50%（pathological fractures excluded）
- •Patients with heart and pulmonary dysfunction> class I
研究组 & 干预措施
modified VCD regimen1
Induction therapy：modified VCD regimen1 for 4 cycles,28 Days per Cycle.Intensive therapy：modified VCD regimen1 for 5 cycles.
Maintenance treatment:CP for 12 cycles. Interval between every two cycles for one month.
Interventions:
Drug: Bortezomib 1.6mg/m2 SC,Days 1, 6, 11, 16; Drug:Cyclophosphamide 300mg/m2 VD,Days 1-3; Drug: Dexamethasone 40 mg/d VD,Days 1, 6, 11,16; We undertook a pharmacodynamic substudy at selected sites. Blood samples were collected in cycle 1 on day 1, 6,11,16 before the dose was given and at several time points after dosing. We analysed whole blood samples to measure 20S proteasome chymotryptic activity, with a standard method. Pharmacodynamic parameters were calculated by analysis of percentage inhibition of 20S proteasome activity-time data.
干预措施: Bortezomib (Drug)
modified VCD regimen1
Induction therapy：modified VCD regimen1 for 4 cycles,28 Days per Cycle.Intensive therapy：modified VCD regimen1 for 5 cycles.
Maintenance treatment:CP for 12 cycles. Interval between every two cycles for one month.
Interventions:
Drug: Bortezomib 1.6mg/m2 SC,Days 1, 6, 11, 16; Drug:Cyclophosphamide 300mg/m2 VD,Days 1-3; Drug: Dexamethasone 40 mg/d VD,Days 1, 6, 11,16; We undertook a pharmacodynamic substudy at selected sites. Blood samples were collected in cycle 1 on day 1, 6,11,16 before the dose was given and at several time points after dosing. We analysed whole blood samples to measure 20S proteasome chymotryptic activity, with a standard method. Pharmacodynamic parameters were calculated by analysis of percentage inhibition of 20S proteasome activity-time data.
干预措施: cyclophosphamide (Drug)
modified VCD regimen1
Induction therapy：modified VCD regimen1 for 4 cycles,28 Days per Cycle.Intensive therapy：modified VCD regimen1 for 5 cycles.
Maintenance treatment:CP for 12 cycles. Interval between every two cycles for one month.
Interventions:
Drug: Bortezomib 1.6mg/m2 SC,Days 1, 6, 11, 16; Drug:Cyclophosphamide 300mg/m2 VD,Days 1-3; Drug: Dexamethasone 40 mg/d VD,Days 1, 6, 11,16; We undertook a pharmacodynamic substudy at selected sites. Blood samples were collected in cycle 1 on day 1, 6,11,16 before the dose was given and at several time points after dosing. We analysed whole blood samples to measure 20S proteasome chymotryptic activity, with a standard method. Pharmacodynamic parameters were calculated by analysis of percentage inhibition of 20S proteasome activity-time data.
干预措施: Dexamethasone (Drug)
modified VCD regimen2
Induction therapy：modified VCD regimen1 for 4 cycles,28 Days per Cycle.Intensive therapy：modified VCD regimen 2 for 5 cycles.
Maintenance treatment:CP for 12 cycles. Interval between every two cycles for one month.
Interventions:
Drug: Bortezomib 1.3mg/m2 SC,Days 1, 6, 11, 16; Drug:Cyclophosphamide 300mg/m2 VD,Days 1-3; Drug: Dexamethasone 40 mg/d VD,Days 1, 6, 11,16; We undertook a pharmacodynamic substudy at selected sites. Blood samples were collected in cycle 1 on day 1, 6,11,16 before the dose was given and at several time points after dosing. We analysed whole blood samples to measure 20S proteasome chymotryptic activity, with a standard method. Pharmacodynamic parameters were calculated by analysis of percentage inhibition of 20S proteasome activity-time data.
干预措施: Bortezomib (Drug)
modified VCD regimen2
Induction therapy：modified VCD regimen1 for 4 cycles,28 Days per Cycle.Intensive therapy：modified VCD regimen 2 for 5 cycles.
Maintenance treatment:CP for 12 cycles. Interval between every two cycles for one month.
Interventions:
Drug: Bortezomib 1.3mg/m2 SC,Days 1, 6, 11, 16; Drug:Cyclophosphamide 300mg/m2 VD,Days 1-3; Drug: Dexamethasone 40 mg/d VD,Days 1, 6, 11,16; We undertook a pharmacodynamic substudy at selected sites. Blood samples were collected in cycle 1 on day 1, 6,11,16 before the dose was given and at several time points after dosing. We analysed whole blood samples to measure 20S proteasome chymotryptic activity, with a standard method. Pharmacodynamic parameters were calculated by analysis of percentage inhibition of 20S proteasome activity-time data.
干预措施: cyclophosphamide (Drug)
modified VCD regimen2
Induction therapy：modified VCD regimen1 for 4 cycles,28 Days per Cycle.Intensive therapy：modified VCD regimen 2 for 5 cycles.
Maintenance treatment:CP for 12 cycles. Interval between every two cycles for one month.
Interventions:
Drug: Bortezomib 1.3mg/m2 SC,Days 1, 6, 11, 16; Drug:Cyclophosphamide 300mg/m2 VD,Days 1-3; Drug: Dexamethasone 40 mg/d VD,Days 1, 6, 11,16; We undertook a pharmacodynamic substudy at selected sites. Blood samples were collected in cycle 1 on day 1, 6,11,16 before the dose was given and at several time points after dosing. We analysed whole blood samples to measure 20S proteasome chymotryptic activity, with a standard method. Pharmacodynamic parameters were calculated by analysis of percentage inhibition of 20S proteasome activity-time data.
干预措施: Dexamethasone (Drug)
结局指标
主要结局
the rate of complete remission
时间窗: Day 1 of every treatment cycle
The rate of complete remission of modified VCD regimens in patients with MM assessed by International Myeloma Working Group(IMWG) criteria.
次要结局
- progression free survival(up to two year)
- Adverse Events(up to two years)
- overall response rates (ORR)(Day 1 of every treatment cycle)
- duration of response(up to 6 months)
- overall survival (OS)(up to two year)
研究者
Yongping Zhai
Department of hemotology
Jinling Hospital, China