Trial Outcomes & Findings for A Study of Subcutaneous and Intravenous VELCADE in Patients With Previously Treated Multiple Myeloma (NCT NCT00722566)
NCT ID: NCT00722566
Last Updated: 2011-10-10
Results Overview
Disease response was measured according to European Group for Blood and Marrow Transplantation (EBMT) criteria with the addition of the response categories of nCR and VGPR. Complete response requires disappearance of monoclonal protein from the blood and urine and \<5% plasma cells in the bone marrow on at least 2 determinations for a minimum of 6 weeks. Partial Response requires ≥50% reduction in serum m-protein for at least 2 determinations at least 6 weeks apart and if present, reduction in 24-hour urinary light chain excretion by either ≥90% or to \<200 mg
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
222 participants
Primary outcome timeframe
Over 4 cycles (prior to the addition of dexamethasone)
Results posted on
2011-10-10
Participant Flow
Participant milestones
| Measure |
VELCADE Subcutaneous
VELCADE 1.3 mg/m\^2 administered by subcutaneous injection on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles.
|
VELCADE Intravenous
VELCADE 1.3 mg/m\^2 administered by intravenous infusion on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles.
|
|---|---|---|
|
Overall Study
STARTED
|
148
|
74
|
|
Overall Study
COMPLETED
|
81
|
39
|
|
Overall Study
NOT COMPLETED
|
67
|
35
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study of Subcutaneous and Intravenous VELCADE in Patients With Previously Treated Multiple Myeloma
Baseline characteristics by cohort
| Measure |
VELCADE Subcutaneous
n=148 Participants
VELCADE 1.3 mg/m\^2 administered by subcutaneous injection on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles.
|
VELCADE Intravenous
n=74 Participants
VELCADE 1.3 mg/m\^2 administered by intravenous infusion on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles.
|
Total
n=222 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
74 Participants
n=5 Participants
|
37 Participants
n=7 Participants
|
111 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
74 Participants
n=5 Participants
|
37 Participants
n=7 Participants
|
111 Participants
n=5 Participants
|
|
Age Continuous
|
64.3 years
STANDARD_DEVIATION 8.96 • n=5 Participants
|
64.0 years
STANDARD_DEVIATION 12.11 • n=7 Participants
|
64.2 years
STANDARD_DEVIATION 10.09 • n=5 Participants
|
|
Sex: Female, Male
Female
|
74 Participants
n=5 Participants
|
27 Participants
n=7 Participants
|
101 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
74 Participants
n=5 Participants
|
47 Participants
n=7 Participants
|
121 Participants
n=5 Participants
|
|
Region of Enrollment
France
|
22 participants
n=5 Participants
|
14 participants
n=7 Participants
|
36 participants
n=5 Participants
|
|
Region of Enrollment
Belgium
|
7 participants
n=5 Participants
|
5 participants
n=7 Participants
|
12 participants
n=5 Participants
|
|
Region of Enrollment
Germany
|
2 participants
n=5 Participants
|
4 participants
n=7 Participants
|
6 participants
n=5 Participants
|
|
Region of Enrollment
Netherlands
|
6 participants
n=5 Participants
|
4 participants
n=7 Participants
|
10 participants
n=5 Participants
|
|
Region of Enrollment
United Kingdom
|
6 participants
n=5 Participants
|
3 participants
n=7 Participants
|
9 participants
n=5 Participants
|
|
Region of Enrollment
Ukraine
|
51 participants
n=5 Participants
|
17 participants
n=7 Participants
|
68 participants
n=5 Participants
|
|
Region of Enrollment
Russian Federation
|
26 participants
n=5 Participants
|
9 participants
n=7 Participants
|
35 participants
n=5 Participants
|
|
Region of Enrollment
Poland
|
20 participants
n=5 Participants
|
7 participants
n=7 Participants
|
27 participants
n=5 Participants
|
|
Region of Enrollment
Argentina
|
5 participants
n=5 Participants
|
8 participants
n=7 Participants
|
13 participants
n=5 Participants
|
|
Region of Enrollment
India
|
3 participants
n=5 Participants
|
3 participants
n=7 Participants
|
6 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Over 4 cycles (prior to the addition of dexamethasone)Population: The response-evaluable population was defined as subjects who received at least 1 dose of study drug and had measurable, secretory multiple myeloma, defined as a serum monoclonal IgG or IgM of ≥10 g/L or a serum monoclonal IgA or IgE ≥5 g/L, or a serum monoclonal IgD of ≥0.5g/L, or urine M-protein of ≥200 mg/24 hours, at study entry.
Disease response was measured according to European Group for Blood and Marrow Transplantation (EBMT) criteria with the addition of the response categories of nCR and VGPR. Complete response requires disappearance of monoclonal protein from the blood and urine and \<5% plasma cells in the bone marrow on at least 2 determinations for a minimum of 6 weeks. Partial Response requires ≥50% reduction in serum m-protein for at least 2 determinations at least 6 weeks apart and if present, reduction in 24-hour urinary light chain excretion by either ≥90% or to \<200 mg
Outcome measures
| Measure |
VELCADE Subcutaneuous
n=145 Participants
VELCADE 1.3 mg/m\^2 administered by subcutaneous injection on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles.
|
VELCADE Intravenous
n=73 Participants
VELCADE 1.3 mg/m\^2 administered by intravenous injection on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles.
|
|---|---|---|
|
Number of Patients With Overall Response (Complete Response + Partial Response)
|
61 Participants
|
31 Participants
|
SECONDARY outcome
Timeframe: Over 4 cycles (prior to the addition of dexamethasone)Population: The response-evaluable population was defined as subjects who received at least 1 dose of study drug and had measurable, secretory multiple myeloma, defined as a serum monoclonal IgG or IgM of ≥10 g/L or a serum monoclonal IgA or IgE ≥5 g/L, or a serum monoclonal IgD of ≥0.5g/L, or urine M-protein of ≥200 mg/24 hours, at study entry.
Disease response was measured according to European Group for Blood and Marrow Transplantation (EBMT) criteria with the addition of the response categories of nCR and VGPR. Complete response requires disappearance of monoclonal protein from the blood and urine and \<5% plasma cells in the bone marrow on at least 2 determinations for a minimum of 6 weeks.
Outcome measures
| Measure |
VELCADE Subcutaneuous
n=145 Participants
VELCADE 1.3 mg/m\^2 administered by subcutaneous injection on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles.
|
VELCADE Intravenous
n=73 Participants
VELCADE 1.3 mg/m\^2 administered by intravenous injection on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles.
|
|---|---|---|
|
Number of Patients With Complete Response
|
9 Participants
|
6 Participants
|
Adverse Events
VELCADE Subcutaneous
Serious events: 53 serious events
Other events: 112 other events
Deaths: 0 deaths
VELCADE Intravenous
Serious events: 26 serious events
Other events: 66 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
VELCADE Subcutaneous
n=147 participants at risk
VELCADE 1.3 mg/m\^2 administered by subcutaneous injection on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles.
|
VELCADE Intravenous
n=74 participants at risk
VELCADE 1.3 mg/m\^2 administered by intravenous infusion on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anemia
|
0.00%
0/147
|
1.4%
1/74
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.68%
1/147
|
1.4%
1/74
|
|
Blood and lymphatic system disorders
Splenomegaly
|
0.68%
1/147
|
0.00%
0/74
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.68%
1/147
|
1.4%
1/74
|
|
Cardiac disorders
Angina Pectoris
|
0.68%
1/147
|
0.00%
0/74
|
|
Cardiac disorders
Arrhythmia
|
0.68%
1/147
|
0.00%
0/74
|
|
Cardiac disorders
Arteriosclerosis coronary artery
|
0.68%
1/147
|
0.00%
0/74
|
|
Cardiac disorders
Atrial Fibrillation
|
1.4%
2/147
|
0.00%
0/74
|
|
Cardiac disorders
Bradyarrhythmia
|
0.68%
1/147
|
0.00%
0/74
|
|
Cardiac disorders
Cardiac Arrest
|
0.00%
0/147
|
1.4%
1/74
|
|
Cardiac disorders
Cardiac failure
|
0.68%
1/147
|
0.00%
0/74
|
|
Cardiac disorders
Cardiac failure acute
|
0.68%
1/147
|
0.00%
0/74
|
|
Cardiac disorders
Coronary artery insufficiency
|
0.00%
0/147
|
1.4%
1/74
|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/147
|
1.4%
1/74
|
|
Cardiac disorders
Supraventricular tachycardia
|
0.00%
0/147
|
1.4%
1/74
|
|
Cardiac disorders
Tachycardia paroxysmal
|
0.00%
0/147
|
1.4%
1/74
|
|
Ear and labyrinth disorders
Acute vestibular syndrome
|
0.68%
1/147
|
0.00%
0/74
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.68%
1/147
|
0.00%
0/74
|
|
Gastrointestinal disorders
Abdominal pain
|
0.68%
1/147
|
1.4%
1/74
|
|
Gastrointestinal disorders
Diarrhoea
|
2.0%
3/147
|
4.1%
3/74
|
|
Gastrointestinal disorders
Haematemesis
|
0.68%
1/147
|
0.00%
0/74
|
|
Gastrointestinal disorders
Intestinal obstruction
|
0.68%
1/147
|
0.00%
0/74
|
|
Gastrointestinal disorders
Mallory-Weiss syndrome
|
0.68%
1/147
|
0.00%
0/74
|
|
Gastrointestinal disorders
Nausea
|
0.68%
1/147
|
0.00%
0/74
|
|
Gastrointestinal disorders
Pancreatitis chronic
|
0.68%
1/147
|
0.00%
0/74
|
|
Gastrointestinal disorders
Vomiting
|
0.68%
1/147
|
1.4%
1/74
|
|
General disorders
Asthenia
|
1.4%
2/147
|
0.00%
0/74
|
|
General disorders
Chest pain
|
0.68%
1/147
|
0.00%
0/74
|
|
General disorders
Malaise
|
0.68%
1/147
|
0.00%
0/74
|
|
General disorders
Multi-organ failure
|
0.68%
1/147
|
1.4%
1/74
|
|
General disorders
Pain
|
0.68%
1/147
|
0.00%
0/74
|
|
General disorders
Pyrexia
|
2.7%
4/147
|
0.00%
0/74
|
|
General disorders
Sudden death
|
0.68%
1/147
|
0.00%
0/74
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.68%
1/147
|
0.00%
0/74
|
|
Hepatobiliary disorders
Hepatic failure
|
0.68%
1/147
|
0.00%
0/74
|
|
Hepatobiliary disorders
Hepatic function abnormal
|
0.00%
0/147
|
1.4%
1/74
|
|
Hepatobiliary disorders
Hepatitis toxic
|
0.68%
1/147
|
0.00%
0/74
|
|
Infections and infestations
Bronchitis
|
0.68%
1/147
|
0.00%
0/74
|
|
Infections and infestations
Escherichia sepsis
|
0.00%
0/147
|
1.4%
1/74
|
|
General disorders
Hepatitis C
|
0.68%
1/147
|
0.00%
0/74
|
|
Infections and infestations
Herpes Zoster
|
1.4%
2/147
|
0.00%
0/74
|
|
Infections and infestations
Injection site abscess
|
0.00%
0/147
|
1.4%
1/74
|
|
Infections and infestations
Pneumocystis jiroveci pneumonia
|
0.68%
1/147
|
0.00%
0/74
|
|
Infections and infestations
Pneumonia
|
6.1%
9/147
|
6.8%
5/74
|
|
Infections and infestations
Sepsis
|
0.00%
0/147
|
1.4%
1/74
|
|
Infections and infestations
Sinusitis
|
0.68%
1/147
|
0.00%
0/74
|
|
Infections and infestations
Skin infection
|
0.00%
0/147
|
1.4%
1/74
|
|
Infections and infestations
Urinary tract infection
|
0.68%
1/147
|
0.00%
0/74
|
|
Injury, poisoning and procedural complications
Humerus fracture
|
0.68%
1/147
|
1.4%
1/74
|
|
Injury, poisoning and procedural complications
Perianal haematoma
|
0.68%
1/147
|
0.00%
0/74
|
|
Metabolism and nutrition disorders
Decreased appetite
|
1.4%
2/147
|
0.00%
0/74
|
|
Metabolism and nutrition disorders
Dehydration
|
1.4%
2/147
|
0.00%
0/74
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
0.68%
1/147
|
1.4%
1/74
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.68%
1/147
|
0.00%
0/74
|
|
Metabolism and nutrition disorders
Tumour lysis syndrome
|
1.4%
2/147
|
1.4%
1/74
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/147
|
1.4%
1/74
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/147
|
1.4%
1/74
|
|
Musculoskeletal and connective tissue disorders
Pathological fracture
|
0.68%
1/147
|
0.00%
0/74
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer
|
0.00%
0/147
|
1.4%
1/74
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm
|
0.00%
0/147
|
1.4%
1/74
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Plasmacytoma
|
0.68%
1/147
|
0.00%
0/74
|
|
Nervous system disorders
Brain oedema
|
0.00%
0/147
|
1.4%
1/74
|
|
Nervous system disorders
Cerebrovascular disorder
|
0.00%
0/147
|
1.4%
1/74
|
|
Nervous system disorders
Encephalopathy
|
0.00%
0/147
|
1.4%
1/74
|
|
Nervous system disorders
Ischaemic stroke
|
0.00%
0/147
|
1.4%
1/74
|
|
Nervous system disorders
Neuralgia
|
1.4%
2/147
|
0.00%
0/74
|
|
Nervous system disorders
Paraparesis
|
1.4%
2/147
|
0.00%
0/74
|
|
Nervous system disorders
Paraplegia
|
0.68%
1/147
|
0.00%
0/74
|
|
Nervous system disorders
Peripheral neuropathy motor
|
1.4%
2/147
|
1.4%
1/74
|
|
Nervous system disorders
Peripheral sensorimotor neuropathy
|
0.68%
1/147
|
0.00%
0/74
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
1.4%
2/147
|
2.7%
2/74
|
|
Nervous system disorders
Spinal cord compression
|
0.68%
1/147
|
0.00%
0/74
|
|
Nervous system disorders
Syncope
|
0.00%
0/147
|
1.4%
1/74
|
|
Nervous system disorders
Toxic encephalopathy
|
0.68%
1/147
|
0.00%
0/74
|
|
Nervous system disorders
Vascular encephalopathy
|
0.00%
0/147
|
1.4%
1/74
|
|
Psychiatric disorders
Confusional state
|
0.00%
0/147
|
1.4%
1/74
|
|
Psychiatric disorders
Neurosis
|
0.68%
1/147
|
0.00%
0/74
|
|
Renal and urinary disorders
Dysuria
|
0.68%
1/147
|
0.00%
0/74
|
|
Renal and urinary disorders
Haematuria
|
0.68%
1/147
|
0.00%
0/74
|
|
Renal and urinary disorders
Renal failure
|
2.0%
3/147
|
2.7%
2/74
|
|
Renal and urinary disorders
Renal failure acute
|
0.68%
1/147
|
0.00%
0/74
|
|
Renal and urinary disorders
Renal impairment
|
0.00%
0/147
|
1.4%
1/74
|
|
Reproductive system and breast disorders
Vulval ulceration
|
0.68%
1/147
|
0.00%
0/74
|
|
Respiratory, thoracic and mediastinal disorders
Allergic bronchitis
|
0.68%
1/147
|
0.00%
0/74
|
|
Respiratory, thoracic and mediastinal disorders
Bronchospasm
|
0.68%
1/147
|
0.00%
0/74
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
1.4%
2/147
|
1.4%
1/74
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.68%
1/147
|
0.00%
0/74
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
1.4%
2/147
|
1.4%
1/74
|
|
Respiratory, thoracic and mediastinal disorders
Lung disorder
|
0.00%
0/147
|
1.4%
1/74
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
0.68%
1/147
|
0.00%
0/74
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/147
|
1.4%
1/74
|
|
Respiratory, thoracic and mediastinal disorders
Pleurisy
|
0.68%
1/147
|
1.4%
1/74
|
|
Renal and urinary disorders
Urinary retention
|
0.68%
1/147
|
0.00%
0/74
|
|
Vascular disorders
Haematoma
|
0.68%
1/147
|
0.00%
0/74
|
|
Vascular disorders
Hypotension
|
0.00%
0/147
|
1.4%
1/74
|
|
Vascular disorders
Orthostatic hypotension
|
1.4%
2/147
|
1.4%
1/74
|
Other adverse events
| Measure |
VELCADE Subcutaneous
n=147 participants at risk
VELCADE 1.3 mg/m\^2 administered by subcutaneous injection on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles.
|
VELCADE Intravenous
n=74 participants at risk
VELCADE 1.3 mg/m\^2 administered by intravenous infusion on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles.
|
|---|---|---|
|
Blood and lymphatic system disorders
Leukopenia
|
19.7%
29/147
|
21.6%
16/74
|
|
Gastrointestinal disorders
Abdominal pain upper
|
2.0%
3/147
|
10.8%
8/74
|
|
Gastrointestinal disorders
Constipation
|
14.3%
21/147
|
14.9%
11/74
|
|
Gastrointestinal disorders
Dyspepsia
|
2.7%
4/147
|
9.5%
7/74
|
|
General disorders
Chills
|
4.1%
6/147
|
5.4%
4/74
|
|
General disorders
Fatigue
|
11.6%
17/147
|
20.3%
15/74
|
|
General disorders
Oedema peripheral
|
6.1%
9/147
|
8.1%
6/74
|
|
Infections and infestations
Nasopharyngitis
|
2.7%
4/147
|
8.1%
6/74
|
|
Infections and infestations
Upper respiratory tract infection
|
4.8%
7/147
|
9.5%
7/74
|
|
Investigations
Weight decreased
|
15.0%
22/147
|
2.7%
2/74
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
4.8%
7/147
|
6.8%
5/74
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
4.8%
7/147
|
1.4%
1/74
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
8.2%
12/147
|
2.7%
2/74
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
2.7%
4/147
|
6.8%
5/74
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
1.4%
2/147
|
5.4%
4/74
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
5.4%
8/147
|
10.8%
8/74
|
|
Nervous system disorders
Dizziness
|
6.8%
10/147
|
2.7%
2/74
|
|
Nervous system disorders
Headache
|
3.4%
5/147
|
10.8%
8/74
|
|
Nervous system disorders
Paraesthesia
|
6.1%
9/147
|
8.1%
6/74
|
|
Psychiatric disorders
Insomnia
|
12.2%
18/147
|
10.8%
8/74
|
|
Skin and subcutaneous tissue disorders
Pruritis
|
4.8%
7/147
|
2.7%
2/74
|
|
Skin and subcutaneous tissue disorders
Rash
|
6.8%
10/147
|
6.8%
5/74
|
|
Vascular disorders
Hypertension
|
9.5%
14/147
|
4.1%
3/74
|
|
Eye disorders
Chalazion
|
1.4%
2/147
|
5.4%
4/74
|
Additional Information
Helgi Van de Velde, M.D., Ph.D.
Johnson & Johnson Pharmaceutical Research & Development
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place