Trial Outcomes & Findings for An Efficacy and Safety Study of Bortezomib in Participants Previously Treated for Multiple Myeloma With Limited Kidney Function (NCT NCT00718640)

NCT ID: NCT00718640

Last Updated: 2013-10-29

Results Overview

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.

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 10 participants
• Primary outcome timeframe: Week 24 or Early termination visit (30-45 days after last dose)
• Results posted on: 2013-10-29

Participant Flow

Participant milestones

Measure	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).
Overall Study STARTED	10
Overall Study COMPLETED	3
Overall Study NOT COMPLETED	7

Reasons for withdrawal

Measure	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).
Overall Study Adverse Event	4
Overall Study Death	1
Overall Study Unresolved toxicity after 2 weeks	2

Baseline Characteristics

An Efficacy and Safety Study of Bortezomib in Participants Previously Treated for Multiple Myeloma With Limited Kidney Function

Baseline characteristics by cohort

Measure	Bortezomib and Dexamethasone n=10 Participants 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).
Age, Customized < 65	1 participants n=93 Participants
Age, Customized Between 65-69	1 participants n=93 Participants
Age, Customized Between 70-74	4 participants n=93 Participants
Age, Customized >=75	4 participants n=93 Participants
Sex: Female, Male Female	6 Participants n=93 Participants
Sex: Female, Male Male	4 Participants n=93 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

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)

Outcome measures

Outcome data not reported

Adverse Events

Bortezomib and Dexamethasone

Serious events: 4 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Measure	Bortezomib and Dexamethasone n=10 participants at risk 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).
Infections and infestations Pneumonia	10.0% 1/10 • Day 1 up to 30 days after last dose of study medication
Gastrointestinal disorders Diarrhoea	10.0% 1/10 • Day 1 up to 30 days after last dose of study medication
Renal and urinary disorders Renal impairment	10.0% 1/10 • Day 1 up to 30 days after last dose of study medication
Vascular disorders Hypertension	10.0% 1/10 • Day 1 up to 30 days after last dose of study medication
Musculoskeletal and connective tissue disorders Muscle weakness	10.0% 1/10 • Day 1 up to 30 days after last dose of study medication
Nervous system disorders Depressed level of consciousness	10.0% 1/10 • Day 1 up to 30 days after last dose of study medication
Nervous system disorders Aphasia	10.0% 1/10 • Day 1 up to 30 days after last dose of study medication
Nervous system disorders Speech disorder	10.0% 1/10 • Day 1 up to 30 days after last dose of study medication
Psychiatric disorders Confusion state	10.0% 1/10 • Day 1 up to 30 days after last dose of study medication
Gastrointestinal disorders Gastrointestinal haemorrhage	10.0% 1/10 • Day 1 up to 30 days after last dose of study medication
Metabolism and nutrition disorders Dehydration	10.0% 1/10 • Day 1 up to 30 days after last dose of study medication

Other adverse events

Measure	Bortezomib and Dexamethasone n=10 participants at risk 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).
Vascular disorders Hypotension	10.0% 1/10 • Day 1 up to 30 days after last dose of study medication
Vascular disorders Orthostatic hypotension	10.0% 1/10 • Day 1 up to 30 days after last dose of study medication
Vascular disorders Hypertension	10.0% 1/10 • Day 1 up to 30 days after last dose of study medication
Respiratory, thoracic and mediastinal disorders Dyspnoea	20.0% 2/10 • Day 1 up to 30 days after last dose of study medication
Respiratory, thoracic and mediastinal disorders Cough	10.0% 1/10 • Day 1 up to 30 days after last dose of study medication
Psychiatric disorders Mood altered	10.0% 1/10 • Day 1 up to 30 days after last dose of study medication
Psychiatric disorders Confusional state	10.0% 1/10 • Day 1 up to 30 days after last dose of study medication
Nervous system disorders Peripheral sensory neuropathy	10.0% 1/10 • Day 1 up to 30 days after last dose of study medication
Nervous system disorders Neuropathy peripheral	10.0% 1/10 • Day 1 up to 30 days after last dose of study medication
Nervous system disorders Neuralgia	20.0% 2/10 • Day 1 up to 30 days after last dose of study medication
Musculoskeletal and connective tissue disorders Muscular weakness	20.0% 2/10 • Day 1 up to 30 days after last dose of study medication
Metabolism and nutrition disorders Hypokalaemia	20.0% 2/10 • Day 1 up to 30 days after last dose of study medication
Metabolism and nutrition disorders Hypocalcaemia	10.0% 1/10 • Day 1 up to 30 days after last dose of study medication
Metabolism and nutrition disorders Anorexia	10.0% 1/10 • Day 1 up to 30 days after last dose of study medication
Investigations International normalised ratio increased	10.0% 1/10 • Day 1 up to 30 days after last dose of study medication
Investigations Blood creatinine increased	40.0% 4/10 • Day 1 up to 30 days after last dose of study medication
Investigations Blood albumin decreased	10.0% 1/10 • Day 1 up to 30 days after last dose of study medication
Injury, poisoning and procedural complications Contusion	10.0% 1/10 • Day 1 up to 30 days after last dose of study medication
Infections and infestations Herpes zoster	10.0% 1/10 • Day 1 up to 30 days after last dose of study medication
Infections and infestations Bacteraemia	10.0% 1/10 • Day 1 up to 30 days after last dose of study medication
General disorders Fatigue	20.0% 2/10 • Day 1 up to 30 days after last dose of study medication
General disorders Asthenia	10.0% 1/10 • Day 1 up to 30 days after last dose of study medication
Gastrointestinal disorders Vomiting	10.0% 1/10 • Day 1 up to 30 days after last dose of study medication
Gastrointestinal disorders Diarrhoea	10.0% 1/10 • Day 1 up to 30 days after last dose of study medication
Gastrointestinal disorders Constipation	10.0% 1/10 • Day 1 up to 30 days after last dose of study medication
Gastrointestinal disorders Abdominal pain	10.0% 1/10 • Day 1 up to 30 days after last dose of study medication
Blood and lymphatic system disorders Thrombocytopenia	30.0% 3/10 • Day 1 up to 30 days after last dose of study medication
Blood and lymphatic system disorders Lymphopenia	10.0% 1/10 • Day 1 up to 30 days after last dose of study medication
Blood and lymphatic system disorders Leukopenia	10.0% 1/10 • Day 1 up to 30 days after last dose of study medication
Blood and lymphatic system disorders Anaemia	20.0% 2/10 • Day 1 up to 30 days after last dose of study medication

Additional Information

Director, Medical Affairs Oncology

Janssen Inc., Canada

Phone: 416-382-5078

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place