Tolerability and Efficacy of Modified VCD Regimens in Previously Untreated Multiple Myeloma.

Study Overview
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Brief Summary
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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.

Official Title
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Randomized, Multicenter Study of Tolerability and Efficacy of Modified Combinations of Bortezomib, Dexamethasone and Cyclophosphamide in Previously Untreated Multiple Myeloma.

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: Bortezomib
* Drug: cyclophosphamide
* Drug: Dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: modified VCD regimen1<br>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. | Drug: Bortezomib<br>* Induction therapy：1.6mg/m2 or 1.3mg/m2 SC,Days 1, 6, 11, 16 of each 28 day cycles,4 cycle Intensive therapy：1.6mg/m2 or 1.3mg/m2 SC,Days 1, 6, 11, 16 of each 28 day cycles,5 cycles.<br>* Other names: Velcade;Drug: cyclophosphamide<br>* Induction therapy：300mg/m2 VD Days 1-3 of each 28 day cycles,4 cycles. Intensive therapy：300mg/m2 VD Days 1-3 of each 28 day cycles,5 cycles. Maintenance treatment with CP: 200mg PO Days 1-14 of each 28 day cycles,12 cycles.<br>* Other names: Endoxan, Cytoxan, Neosar, Procytox, Revimmune;Drug: Dexamethasone<br>* Induction therapy：40 mg/d VD Days 1,6,11,16 of each 28 day cycles,4 cycles Intensive therapy：40 mg/d VD Days 1,6,11,16 of each 28 day cycles,5 cycles.<br>* Other names: Acidocont,Deronil,Dexacortal,dexametona,Flumeprednisolon;|
| Experimental: modified VCD regimen2<br>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. | Drug: Bortezomib<br>* Induction therapy：1.6mg/m2 or 1.3mg/m2 SC,Days 1, 6, 11, 16 of each 28 day cycles,4 cycle Intensive therapy：1.6mg/m2 or 1.3mg/m2 SC,Days 1, 6, 11, 16 of each 28 day cycles,5 cycles.<br>* Other names: Velcade;Drug: cyclophosphamide<br>* Induction therapy：300mg/m2 VD Days 1-3 of each 28 day cycles,4 cycles. Intensive therapy：300mg/m2 VD Days 1-3 of each 28 day cycles,5 cycles. Maintenance treatment with CP: 200mg PO Days 1-14 of each 28 day cycles,12 cycles.<br>* Other names: Endoxan, Cytoxan, Neosar, Procytox, Revimmune;Drug: Dexamethasone<br>* Induction therapy：40 mg/d VD Days 1,6,11,16 of each 28 day cycles,4 cycles Intensive therapy：40 mg/d VD Days 1,6,11,16 of each 28 day cycles,5 cycles.<br>* Other names: Acidocont,Deronil,Dexacortal,dexametona,Flumeprednisolon;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the rate of complete remission | The rate of complete remission of modified VCD regimens in patients with MM assessed by International Myeloma Working Group(IMWG) criteria. | Day 1 of every treatment cycle | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression free survival | PFS of modified VCD regimens in patients with MM assessed by International Myeloma Working Group(IMWG) criteria. | up to two year | 
| Adverse Events | Adverse events (AEs) were graded according to NCI-CTCAE Version 4.0 | up to two years | 
| overall response rates (ORR) | The rate of overall response of modified VCD regimens in patients with MM assessed by International Myeloma Working Group(IMWG) criteria. | Day 1 of every treatment cycle | 
| duration of response | Duration of response of modified VCD regimens in patients with MM assessed by International Myeloma Working Group(IMWG) criteria. | up to 6 months | 
| overall survival (OS) | The rate of OS of modified VCD regimens in patients with MM assessed by International Myeloma Working Group(IMWG) criteria. | up to two year |