Multiple Myeloma
Conditions
Keywords
Multiple Myeloma, Velcade, Bortezomib, Dexamethasone
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.
Interventions
DRUGDexamethasone
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).
DRUGBortezomib
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.
Sponsors
Janssen-Ortho Inc., Canada
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Renal Compromised Multiple Myeloma by International Myeloma Working Group (IMWG) Uniform Response Criteria | Week 24 or Early termination visit (30-45 days after last dose) | 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
| Measure | Time frame | Description |
|---|---|---|
| Time to Progression (TTP) of Disease | Day 1 (Start of treatment) until the date of first documented evidence of progression of disease or death | 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 | Day 1 (Start of treatment) until the date of first documented achievement 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 | Day 1 of Cycle 1, 3, 5, 7 and Final visit/Early termination visit (30-45 days after last dose) | 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. |
| Best Response to Treatment | Day 1 of Cycle 1, 2, 3, 4, 5, 5, 6, 7, 8 and Final/Early termination visit (30-45 days after last dose) | 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. |
| Quality of Life Assessment by QLQ C-30 | Final Visit/Early termination visit (30-45 days after last dose) | 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) | Quality of Life (EQ-5D) Final Visit/Early termination visit (30-45 days after last dose) | 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 | Day 1 of Cycle 1, 2, 3, 4, 5, 5, 6, 7, 8 and Final/Early termination visit (30-45 days after last dose) | 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) |
| Karnofsky Performance Status (KPS) Score | Day 1 of Cycle 1, 3, 5, 7 and Final visit (30-45 days after last dose) or early termination visit | 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. |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bortezomib and Dexamethasone 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). | 10 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 4 |
| Overall Study | Death | 1 |
| Overall Study | Unresolved toxicity after 2 weeks | 2 |
Baseline characteristics
| Characteristic | Bortezomib and Dexamethasone |
|---|---|
| Age, Customized < 65 | 1 participants |
| Age, Customized >=75 | 4 participants |
| Age, Customized Between 65-69 | 1 participants |
| Age, Customized Between 70-74 | 4 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 9 / 10 |
| serious Total, serious adverse events | 4 / 10 |
Outcome results
Primary
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.
Time frame: Week 24 or Early termination visit (30-45 days after last dose)
Population: The study was terminated. Due to insufficient number of participants, the outcome measure data was not analyzed.
Secondary
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 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)
Population: The study was terminated. Due to insufficient number of participants, the outcome measure data was not analyzed.
Secondary
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.
Time frame: Day 1 (Start of treatment) until the date of first documented achievement of response
Population: The study was terminated. Due to insufficient number of participants, the outcome measure data was not analyzed.
Secondary
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.
Time frame: Day 1 of Cycle 1, 3, 5, 7 and Final visit/Early termination visit (30-45 days after last dose)
Population: The study was terminated. Due to insufficient number of participants, the outcome measure data was not analyzed.
Secondary
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.
Time frame: Day 1 of Cycle 1, 3, 5, 7 and Final visit (30-45 days after last dose) or early termination visit
Population: The study was terminated. Due to insufficient number of participants, the outcome measure data was not analyzed.
Secondary
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.
Time frame: Quality of Life (EQ-5D) Final Visit/Early termination visit (30-45 days after last dose)
Population: The study was terminated. Due to insufficient number of participants, the outcome measure data was not analyzed.
Secondary
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.
Time frame: Final Visit/Early termination visit (30-45 days after last dose)
Population: The study was terminated. Due to insufficient number of participants, the outcome measure data was not analyzed.
Secondary
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)
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)
Population: The study was terminated. Due to insufficient number of participants, the outcome measure data was not analyzed.
Secondary
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.
Time frame: Day 1 (Start of treatment) until the date of first documented evidence of progression of disease or death
Population: The study was terminated. Due to insufficient number of participants, the outcome measure data was not analyzed.