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

• ClinicalTrials.gov Identifier: NCT00833560
• Recruitment Status: Completed
• First Posted: February 2, 2009
• Results First Posted: March 3, 2014
• Last Update Posted: November 21, 2014
• Sponsor: Janssen-Cilag G.m.b.H
• Information provided by (Responsible Party): Janssen-Cilag G.m.b.H

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Multiple Myeloma	Drug: Cyclophosphamide; Drug: Bortezomib; Drug: Dexamethasone	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 401 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Study Start Date: March 2006
• Actual Primary Completion Date: June 2009
• Actual Study Completion Date: June 2009

Arms and Interventions

Arm

Intervention/treatment

Experimental: Cyclophosphamide + Bortezomib + Dexamethasone; 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; 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.; Drug: Bortezomib; 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).; Other Name: VELCADE; Drug: Dexamethasone; 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).

Outcome Measures

Primary Outcome Measures :

1. Participants With Complete Response (CR) + Partial Response (PR) (Efficacy Set) [ Time Frame: 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 :

1. Participants With Complete Response (CR) + Partial Response (PR) (Per-protocol Analysis Set) [ Time Frame: 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.
2. Percentage of Participants With Complete Response + Partial Response in Relation to Cytogenetic Subgroups (Efficacy Set) [ Time Frame: 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
3. Percentage of Participants With Complete Response + Partial Response in Relation to Cytogenetic Subgroups (Per-protocol Set) [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Germany

Berg, Germany

Berlin, Germany

Bremen, Germany

Dresden, Germany

Erlangen, Germany

Frankfurt / Main, Germany

Freiburg, Germany

Greifswald, Germany

Göttingen, Germany

Halle, Germany

Hamburg, Germany

Hamm, Germany

Hannover, Germany

Homburg, Germany

Jena, Germany

Karlsruhe, Germany

Kiel, Germany

Lübeck, Germany

Magdeburg, Germany

Mainz, Germany

Muenchen, Germany

Mutlangen, Germany

München, Germany

Münster, Germany

Nürnberg, Germany

Oldenburg, Germany

Potsdam, Germany

Regensburg, Germany

Rehling, Germany

Rostock, Germany

Stuttgart, Germany

Tübingen, Germany

Ulm, Germany

Villingen-Schwenningen, Germany

Würzburg, Germany

Sponsors and Collaborators

Janssen-Cilag G.m.b.H

Investigators

• Study Director: Janssen-Cilag G.m.b.H, Germany Clinical Trial; Janssen-Cilag G.m.b.H

More Information

• Responsible Party: Janssen-Cilag G.m.b.H
• ClinicalTrials.gov Identifier: NCT00833560
• Other Study ID Numbers: CR005242; 26866138MMY2031 ( Other Identifier: Janssen-Cilag G.m.b.H, Germany ); 2005-003902-27 ( EudraCT Number )
• First Posted: February 2, 2009
• Results First Posted: March 3, 2014
• Last Update Posted: November 21, 2014
• Last Verified: November 2014

Keywords provided by Janssen-Cilag G.m.b.H:

Multiple Myeloma; Untreated multiple myeloma; Bortezomib; VELCADE; Cyclophosphamide; Dexamethasone; Chemotherapy; Remission therapy; Induction therapy; Stem Cell Transplantation

Additional relevant MeSH terms:

Multiple Myeloma; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Dexamethasone; Cyclophosphamide; Bortezomib; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Myeloablative Agonists; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents