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

Yongping Zhai

Status and phase: Unknown; Phase 2

Conditions: Multiple Myeloma

Treatments: Drug: Bortezomib; Drug: Dexamethasone; Drug: cyclophosphamide

Study type: Interventional

Funder types: Other

Identifiers

NCT02086942

NAB20130806

Details and patient eligibility

About

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.

Enrollment: 94 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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94 participants in 2 patient groups

modified VCD regimen1

Experimental group

Description:

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.

Treatment:

Drug: cyclophosphamide

Drug: Dexamethasone

Drug: Bortezomib

modified VCD regimen2

Experimental group

Description:

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.

Treatment:

Drug: cyclophosphamide

Drug: Dexamethasone

Drug: Bortezomib