Tolerability and Efficacy of Modified VCD Regimens in Previously Untreated Multiple Myeloma.
- Conditions
- Multiple Myeloma
- Interventions
- Registration Number
- NCT02086942
- Lead Sponsor
- Yongping Zhai
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 94
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description modified VCD regimen1 Bortezomib 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. modified VCD regimen1 cyclophosphamide 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. modified VCD regimen1 Dexamethasone 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. modified VCD regimen2 cyclophosphamide 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. modified VCD regimen2 Bortezomib 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. modified VCD regimen2 Dexamethasone 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.
- Primary Outcome Measures
Name Time Method the rate of complete remission 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.
- Secondary Outcome Measures
Name Time Method progression free survival up to two year PFS of modified VCD regimens in patients with MM assessed by International Myeloma Working Group(IMWG) criteria.
Adverse Events up to two years Adverse events (AEs) were graded according to NCI-CTCAE Version 4.0
overall response rates (ORR) Day 1 of every treatment cycle The rate of overall response of modified VCD regimens in patients with MM assessed by International Myeloma Working Group(IMWG) criteria.
duration of response up to 6 months Duration of response of modified VCD regimens in patients with MM assessed by International Myeloma Working Group(IMWG) criteria.
overall survival (OS) up to two year The rate of OS of modified VCD regimens in patients with MM assessed by International Myeloma Working Group(IMWG) criteria.
Trial Locations
- Locations (1)
Jinling Hospital
🇨🇳Nanjing, Jiangsu, China