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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Clinical Study on Induction of Remission Using Bortezomib (Vel), Cyclophosphamide (C), and Dexamethasone (D) in Patients Until 60 Years of Age With Untreated Multiple Myeloma and Planned for a High Dose Chemotherapy: (VelCD; Deutsche Studiengruppe Multiples Myelom [DSMM] XIa)

Conditions
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Multiple Myeloma

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


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cyclophosphamide + Bortezomib + Dexamethasone<br>Part 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. | Drug: Cyclophosphamide<br>* In Part 1, cyclophosphamide with dose ranging from 900 to 1500 mg will be administered intravenously on Day 1 of each 21 day cycle for 3 cycles to determine optimal dose. In Part 2, optimal dose determined in Part 1 will be administered on Day 1 of each 21 day cycle for 3 cycles.<br>Drug: Bortezomib<br>* Bortezomib 1.3 mg/m2 will be administered intravenously on Days 1,4,8, and 11 of each 21 day cycle for 3 cycles in both parts (Part 1 and Part 2).<br>* Other names: VELCADE;Drug: Dexamethasone<br>* Participants will receive dexamethasone 40 mg orally or intravenously on Days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21 day cycle for 3 cycles in both parts (Part 1 and Part 2).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participants With Complete Response (CR) + Partial Response (PR) (Efficacy Set) | 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. | Up to Day 63 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participants With Complete Response (CR) + Partial Response (PR) (Per-protocol Analysis Set) | 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. | Up to Day 63 | 
| Percentage of Participants With Complete Response + Partial Response in Relation to Cytogenetic Subgroups (Efficacy Set) | 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 | Up to Day 63 | 
| Percentage of Participants With Complete Response + Partial Response in Relation to Cytogenetic Subgroups (Per-protocol Set) | 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. | Up to Day 63 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Myeloma, Untreated multiple myeloma, Bortezomib, VELCADE, Cyclophosphamide, Dexamethasone, Chemotherapy, Remission therapy, Induction therapy, Stem Cell Transplantation