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A Study of Bortezomib, Cyclophosphamide, and Dexamethasone in Patients With Untreated Multiple Myeloma and Planned for a High Dose Chemotherapy

Phase 2
Completed
Conditions
Multiple Myeloma
Interventions
Registration Number
NCT00833560
Lead Sponsor
Janssen-Cilag G.m.b.H
Brief Summary

The purpose of this study is to evaluate the safety and effectiveness of bortezomib in combination with a standard regimen of cyclophosphamide and dexamethasone.

Detailed Description

This is open-label (both the participant and the investigator know what treatment participants will receive), prospective (participants are identified and then followed forward in time for the outcome of the study), multi-centre, and non-randomized (participants are assigned to different treatment groups by the investigator) study. The study will be conducted into 2 parts (Part 1 and Part 2). Approximately 400 participants will be enrolled (30 in Part 1 and 370 in Part 2). In Part 1 the optimum dose of cyclophosphamide will be evaluated and in Part 2 the selected dose of cyclophosphamide from Part 1 will be administered. Part 2 will include a screening period of a maximum of 14 days followed by chemotherapy (bortezomib, cyclophosphamide, and dexamethasone) of a maximum of three 21-day cycles. Safety will be evaluated by the assessment of adverse events, vital signs, physical examination, electrocardiogram, and clinical laboratory tests which will be monitored throughout the study.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
401
Inclusion Criteria
  • Cytologically or histologically diagnosed with multiple myeloma stage II/III
  • Participants without preceding cytostatic (tending to retard cellular activity and multiplication) treatment (pretreatment with radiation or dexamethasone is allowed)
  • Agree to use one of the contraception methods as defined in the protocol
  • Karnofsky performance status 60 percent or more
  • Adequate laboratory test values
Exclusion Criteria
  • Non-secretory multiple myeloma
  • Estimated life expectancy less than 3 months
  • History of cancer (except basal cell carcinoma) in the last 5 years
  • Peripheral neuropathy (disorder of the peripheral nerves) grade 2 or more
  • Positive human immunodeficiency virus test and active hepatitis B and/or hepatitis C
  • Pregnant or breast-feeding female participants

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Cyclophosphamide + Bortezomib + DexamethasoneBortezomibPart 1 will be the dose titration part for cyclophosphamide. Participants will receive cyclophosphamide, bortezomib, and dexamethasone for 3 cycles. In Part 2, participants will receive cyclophosphamide (dose determined in Part 1) with pre-defined dose of bortezomib and dexamethasone for 3 cycles.
Cyclophosphamide + Bortezomib + DexamethasoneDexamethasonePart 1 will be the dose titration part for cyclophosphamide. Participants will receive cyclophosphamide, bortezomib, and dexamethasone for 3 cycles. In Part 2, participants will receive cyclophosphamide (dose determined in Part 1) with pre-defined dose of bortezomib and dexamethasone for 3 cycles.
Cyclophosphamide + Bortezomib + DexamethasoneCyclophosphamidePart 1 will be the dose titration part for cyclophosphamide. Participants will receive cyclophosphamide, bortezomib, and dexamethasone for 3 cycles. In Part 2, participants will receive cyclophosphamide (dose determined in Part 1) with pre-defined dose of bortezomib and dexamethasone for 3 cycles.
Primary Outcome Measures
NameTimeMethod
Participants With Complete Response (CR) + Partial Response (PR) (Efficacy Set)Up to Day 63

CR and PR are defined by the local investigator according to the current European Group for Blood and Marrow Transplantation (EBMT) criteria. According to EBMT criteria, CR is defined as the absence of serum and urine monoclonal paraprotein + no increase in size or number of lytic bone lesions; and PR is defined as not all CR criteria + 50 percentage or more reduction in serum monoclonal paraprotein.

Secondary Outcome Measures
NameTimeMethod
Percentage of Participants With Complete Response + Partial Response in Relation to Cytogenetic Subgroups (Efficacy Set)Up to Day 63

Response rate was defined as the percentage of participants with response of combined CR+PR according to the EBMT criteria. As per the EBMT criteria, CR is defined as the absence of serum and urine monoclonal paraprotein and no increase in size or number of lytic bone lesions; PR is defined as not all CR criteria and 50 percentage or more reduction in serum monoclonal paraprotein. Percentage of participants with complete or partial response that carried the indicated cytogenetic marker is reported. Same participant could count in more than one category due to multiple responses possible

Percentage of Participants With Complete Response + Partial Response in Relation to Cytogenetic Subgroups (Per-protocol Set)Up to Day 63

Response rate was defined as the percentage of participants with response of combined CR+PR according to the EBMT criteria. As per the EBMT criteria, CR is defined as the absence of serum and urine monoclonal paraprotein and no increase in size or number of lytic bone lesions; PR is defined as not all CR criteria and 50 percentage or more reduction in serum monoclonal paraprotein. Percentage of participants with complete or partial response that carried the indicated cytogenetic marker is reported. Same participant could count in more than one category due to multiple responses possible.

Participants With Complete Response (CR) + Partial Response (PR) (Per-protocol Analysis Set)Up to Day 63

CR and PR are defined by the local investigator according to the current European Group for Blood and Marrow Transplantation (EBMT) criteria. According to EBMT criteria, CR is defined as the absence of serum and urine monoclonal paraprotein + no increase in size or number of lytic bone lesions; and PR is defined as not all CR criteria + 50 percentage or more reduction in serum monoclonal paraprotein.

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