Back to resultsAn Efficacy and Safety Study of Bortezomib in Participants Previously Treated for Multiple Myeloma With Limited Kidney Function
Primary Purpose
Multiple Myeloma
Status
Terminated
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Dexamethasone
Bortezomib
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Myeloma focused on measuring Multiple Myeloma, Velcade, Bortezomib, Dexamethasone
Eligibility Criteria
Inclusion Criteria:
- Participants diagnosed with symptomatic multiple myeloma based on the International Myeloma Working Group (IMWG) criteria; greater than or equal to 10 percent plasma cells in the bone marrow (or tissue biopsy) detected, monoclonal protein in the serum or urine and the, presence of end-organ injury
- Participants with measurable disease defined by at least 1 of the following 5 measurements: a) serum M-protein greater than or equal to 1 gram per deciliter (g/dl), b) Urine M Protein greater than or equal to 200 milligram per 24 hour, c) Serum free light chain (FLC) assay: Involved FLC level greater than 10 mg per dl (mg/dl) provided serum FLC ratio is abnormal, d) Bone marrow plasma cells greater than or equal to 30 percent
- Participants who received at least 1 prior line of chemotherapy for multiple myeloma and, is refractory to or has relapsed after the last therapy
- Participants with Karnofsky performance status greater than 60 or Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Participants with calculated or measured creatinine clearance of less than or equal to 30 mililiter per minute (ml/min). During the screening period, 2 measures of creatinine clearance at least 7 days apart must be obtained, and both must be less than 30 ml/min
Exclusion Criteria:
- Participants who had received bortezomib in previous clinical trial and best response was progressive disease or experienced one or more serious events
- Participants who received nitorsoureas within 6 weeks, or 2 consecutive weeks of intense corticosteroids, or immunotherapy or antibody therapy within 4 weeks before enrolment
- Participants with history of allergic reaction attributable to compounds containing boron or mannitol
- Participants with peripheral neuropathy of Grade 2 or greater intensity at the time of signing informed consent form
- Pregnant or breast-feeding female participants
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Bortezomib and Dexamethasone
Arm Description
Bortezomib 1.3 milligram (mg) per meter^2 (m^2) bolus (a large amount) intravenous (into the vein) injection will be administered once daily on Days 1, 4, 8 and 11 of each 21-day cycle with addition of Dexamethasone 20 mg per day administered orally, once daily on Days 1 and 2, Days 4 and 5, Days 8 and 9 and Days 11 and 12 of each 21-day cycle as per Investigator's discretion for those participants who experience disease progression after treatment completion up to Cycle 2 or have no change from Baseline after completion of at least 4 cycles. The treatment will be given up to 8 cycles (24 weeks).
Outcomes
Primary Outcome Measures
Percentage of Participants With Renal Compromised Multiple Myeloma by International Myeloma Working Group (IMWG) Uniform Response Criteria
The IMWG uniform response criteria define; Complete response(CR) as negative immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas and <5% plasma cells in bone marrow(BM). Stringent CR as CR+normal free light chain ratio and absence of clonal cells in BM Very good partial response (PR) as serum and urine M-protein (monoclonal paraprotein) detectable by immunofixation but not on electrophoresis or 90% or >reduction in serum and urine M-protein level <100 milligram(mg) per 24 hour(hr).PR as <=50% reduction of serum and <= 90% of urine M-protein or up to <200 mg/24 hr.
Secondary Outcome Measures
Best Response to Treatment
It was assessed by IMWG criteria. It defines complete response as negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and <5% plasma cells in bone marrow. Very good partial response as serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or > reduction in serum and urine M-protein level<100 mg per 24 hour. Partial Response as <=50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by <=90% or to <200mg per 24 hr.
Time to Progression (TTP) of Disease
The TTP was defined as the time from the date of starting treatment until the date of first documented evidence of progression of disease or death.
Duration of Response
The duration of Response was defined as the time of first recorded achievement of a particular response level, which was defined according to IMWG uniform response criteria, as either complete response, stringent complete response, very good partial response or partial response included only responding participants, until the participants were assessed to have progressive disease.
Eastern Cooperative Oncology Group Performance Status (ECOG PS) Score
The ECOG PS Score 0 versus 1, wherein 0 signifies fully active, able to carry all pre-disease performance without restriction and 1 signifies restriction in physically strenuous activity but ambulatory (able to walk) and able to carry out work on a light or sedentary nature.
Karnofsky Performance Status (KPS) Score
The KPS is used to quantify participant's general well-being and activities of daily life and participants are classified based on their functional impairment. KPS score is 11-level score which ranges between 0 (death) to 100 (no evidence of disease). Higher score means higher ability to perform daily tasks.
Quality of Life Assessment by QLQ C-30
The quality of life was assessed by the questionnaire QLQ C-30 designed by European Organization for the Research and Treatment of Cancer (EORTC). The EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer participants. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the fatigue scale is equal to higher level of symptomatology or problems.
Quality of Life Assessed by Euro Quality of Life (EQ-5D)
The EQ-5D is a participant rated questionnaire to assess health-related quality of life in terms of a single utility score. It assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression where 1=better health state (no problems), 3=worst health state. Scoring formula was developed by Euro quality of life group which assigns a utility value for each domain in profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state.
Renal Function
Renal function was analysed by creatinine clearance. Creatinine clearance was calculated by Cockroft-Gault fourmula. Creatinine clearance is equal to 140 minus age multiplied by weight and constant (1 for men and 0.85 for women) divided by creatinine in (micro mole per liter)
Full Information
NCT ID
NCT00718640
First Posted
July 17, 2008
Last Updated
September 25, 2013
Sponsor
Janssen-Ortho Inc., Canada
1. Study Identification
Unique Protocol Identification Number
NCT00718640
Brief Title
An Efficacy and Safety Study of Bortezomib in Participants Previously Treated for Multiple Myeloma With Limited Kidney Function
Official Title
Safety and Efficacy of Velcade in Relapsed and/or Refractory Multiple Myeloma Patients With Impaired Renal Function
Study Type
Interventional
2. Study Status
Record Verification Date
September 2013
Overall Recruitment Status
Terminated
Why Stopped
Study stopped due to lagging enrolment.
Study Start Date
October 2007 (undefined)
Primary Completion Date
December 2009 (Actual)
Study Completion Date
January 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen-Ortho Inc., Canada
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to evaluate the effectiveness and safety of bortezomib in participants previously treated for multiple myeloma (cancer of plasma cells in bone marrow causing numerous tumors and characterized by the presence of abnormal proteins in the blood) with limited kidney function.
Detailed Description
This is an open label (all people know the identity of the intervention), multi-center (study conducted at multiple sites), non-comparative, single arm study of bortezomib. The study consists of 3 phases: Screening phase (21 days before Day 1 of cycle 1); Treatment phase (consist of 8 cycles each cycle of 21 days or until disease progression or unacceptable toxicity); and a Follow-up phase (for participants with positive treatment response or stable disease at the final visit). Follow-up for disease progression will be done in every 3 months up to 2 years. Participants who will experience disease progression after completing at least 2 cycles of bortezomib treatment or have no change from baseline in stable disease after completing at least 4 cycles or as per Investigator's discretion will receive dexamethasone. Efficacy will be primarily evaluated by percentage of participants with renal compromised Multiple Myeloma by International Myeloma Working Group (IMWG) uniform response criteria. Participants' safety will be monitored throughout the study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
Multiple Myeloma, Velcade, Bortezomib, Dexamethasone
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Bortezomib and Dexamethasone
Arm Type
Experimental
Arm Description
Bortezomib 1.3 milligram (mg) per meter^2 (m^2) bolus (a large amount) intravenous (into the vein) injection will be administered once daily on Days 1, 4, 8 and 11 of each 21-day cycle with addition of Dexamethasone 20 mg per day administered orally, once daily on Days 1 and 2, Days 4 and 5, Days 8 and 9 and Days 11 and 12 of each 21-day cycle as per Investigator's discretion for those participants who experience disease progression after treatment completion up to Cycle 2 or have no change from Baseline after completion of at least 4 cycles. The treatment will be given up to 8 cycles (24 weeks).
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Intervention Description
Dexamethasone 20 mg per day will be administered orally on Days 1 and 2, Days 4 and 5, Days 8 and 9 and Days 11 and 12 of each 21-days cycle as per Investigator's discretion for those participants who experience disease progression after treatment completion up to Cycle 2 or have no change from Baseline after completion of at least 4 cycles. The treatment will be given up to 8 cycles (24 weeks).
Intervention Type
Drug
Intervention Name(s)
Bortezomib
Other Intervention Name(s)
Velcade
Intervention Description
Bortezomib 1.3 milligram per meter^2 (mg/m^2), bolus intravenous injection will be administered on Days 1, 4, 8 and 11 of each 21-day cycle and up to 8 cycles.
Primary Outcome Measure Information:
Title
Percentage of Participants With Renal Compromised Multiple Myeloma by International Myeloma Working Group (IMWG) Uniform Response Criteria
Description
The IMWG uniform response criteria define; Complete response(CR) as negative immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas and <5% plasma cells in bone marrow(BM). Stringent CR as CR+normal free light chain ratio and absence of clonal cells in BM Very good partial response (PR) as serum and urine M-protein (monoclonal paraprotein) detectable by immunofixation but not on electrophoresis or 90% or >reduction in serum and urine M-protein level <100 milligram(mg) per 24 hour(hr).PR as <=50% reduction of serum and <= 90% of urine M-protein or up to <200 mg/24 hr.
Time Frame
Week 24 or Early termination visit (30-45 days after last dose)
Secondary Outcome Measure Information:
Title
Best Response to Treatment
Description
It was assessed by IMWG criteria. It defines complete response as negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and <5% plasma cells in bone marrow. Very good partial response as serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or > reduction in serum and urine M-protein level<100 mg per 24 hour. Partial Response as <=50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by <=90% or to <200mg per 24 hr.
Time Frame
Day 1 of Cycle 1, 2, 3, 4, 5, 5, 6, 7, 8 and Final/Early termination visit (30-45 days after last dose)
Title
Time to Progression (TTP) of Disease
Description
The TTP was defined as the time from the date of starting treatment until the date of first documented evidence of progression of disease or death.
Time Frame
Day 1 (Start of treatment) until the date of first documented evidence of progression of disease or death
Title
Duration of Response
Description
The duration of Response was defined as the time of first recorded achievement of a particular response level, which was defined according to IMWG uniform response criteria, as either complete response, stringent complete response, very good partial response or partial response included only responding participants, until the participants were assessed to have progressive disease.
Time Frame
Day 1 (Start of treatment) until the date of first documented achievement of response
Title
Eastern Cooperative Oncology Group Performance Status (ECOG PS) Score
Description
The ECOG PS Score 0 versus 1, wherein 0 signifies fully active, able to carry all pre-disease performance without restriction and 1 signifies restriction in physically strenuous activity but ambulatory (able to walk) and able to carry out work on a light or sedentary nature.
Time Frame
Day 1 of Cycle 1, 3, 5, 7 and Final visit/Early termination visit (30-45 days after last dose)
Title
Karnofsky Performance Status (KPS) Score
Description
The KPS is used to quantify participant's general well-being and activities of daily life and participants are classified based on their functional impairment. KPS score is 11-level score which ranges between 0 (death) to 100 (no evidence of disease). Higher score means higher ability to perform daily tasks.
Time Frame
Day 1 of Cycle 1, 3, 5, 7 and Final visit (30-45 days after last dose) or early termination visit
Title
Quality of Life Assessment by QLQ C-30
Description
The quality of life was assessed by the questionnaire QLQ C-30 designed by European Organization for the Research and Treatment of Cancer (EORTC). The EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer participants. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the fatigue scale is equal to higher level of symptomatology or problems.
Time Frame
Final Visit/Early termination visit (30-45 days after last dose)
Title
Quality of Life Assessed by Euro Quality of Life (EQ-5D)
Description
The EQ-5D is a participant rated questionnaire to assess health-related quality of life in terms of a single utility score. It assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression where 1=better health state (no problems), 3=worst health state. Scoring formula was developed by Euro quality of life group which assigns a utility value for each domain in profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state.
Time Frame
Quality of Life (EQ-5D) Final Visit/Early termination visit (30-45 days after last dose)
Title
Renal Function
Description
Renal function was analysed by creatinine clearance. Creatinine clearance was calculated by Cockroft-Gault fourmula. Creatinine clearance is equal to 140 minus age multiplied by weight and constant (1 for men and 0.85 for women) divided by creatinine in (micro mole per liter)
Time Frame
Day 1 of Cycle 1, 2, 3, 4, 5, 5, 6, 7, 8 and Final/Early termination visit (30-45 days after last dose)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Participants diagnosed with symptomatic multiple myeloma based on the International Myeloma Working Group (IMWG) criteria; greater than or equal to 10 percent plasma cells in the bone marrow (or tissue biopsy) detected, monoclonal protein in the serum or urine and the, presence of end-organ injury
Participants with measurable disease defined by at least 1 of the following 5 measurements: a) serum M-protein greater than or equal to 1 gram per deciliter (g/dl), b) Urine M Protein greater than or equal to 200 milligram per 24 hour, c) Serum free light chain (FLC) assay: Involved FLC level greater than 10 mg per dl (mg/dl) provided serum FLC ratio is abnormal, d) Bone marrow plasma cells greater than or equal to 30 percent
Participants who received at least 1 prior line of chemotherapy for multiple myeloma and, is refractory to or has relapsed after the last therapy
Participants with Karnofsky performance status greater than 60 or Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
Participants with calculated or measured creatinine clearance of less than or equal to 30 mililiter per minute (ml/min). During the screening period, 2 measures of creatinine clearance at least 7 days apart must be obtained, and both must be less than 30 ml/min
Exclusion Criteria:
Participants who had received bortezomib in previous clinical trial and best response was progressive disease or experienced one or more serious events
Participants who received nitorsoureas within 6 weeks, or 2 consecutive weeks of intense corticosteroids, or immunotherapy or antibody therapy within 4 weeks before enrolment
Participants with history of allergic reaction attributable to compounds containing boron or mannitol
Participants with peripheral neuropathy of Grade 2 or greater intensity at the time of signing informed consent form
Pregnant or breast-feeding female participants
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Inc. Clinical Trial
Organizational Affiliation
Janssen Inc.
Official's Role
Study Director
Facility Information:
City
New Westminster
State/Province
British Columbia
Country
Canada
City
Vancouver
State/Province
British Columbia
Country
Canada
City
London
State/Province
Ontario
Country
Canada
City
Greenfield Park
State/Province
Quebec
Country
Canada
City
Saint John N/A
Country
Canada
12. IPD Sharing Statement
Learn more about this trial
An Efficacy and Safety Study of Bortezomib in Participants Previously Treated for Multiple Myeloma With Limited Kidney Function
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