Multiple Myeloma
Conditions
Brief summary
Randomized, open-label, international, multi-center, Phase 3 study in which patients are randomized to receive VELCADE administered by subcutaneous injection or intravenous infusion.
Interventions
DRUGVELCADE Administered by subcutaneous injection
Patients will receive a 1.3mg/meters(squared)/dose of VELCADE on Days 1,4,8, and 11 of a 3-week cycle
DRUGVELCADE Administered by intravenous infusion
Patients will receive a 1.3mg/meters(squared) dose of VELCADE on Days 1,4,8, and 11 of a 3-week cycle.
Sponsors
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Millennium Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female subjects 18 years or older 2. Diagnosis of multiple myeloma 3. Measurable, secretory multiple myeloma defined as serum monoclonal IgG of ≥10 g/L, serum monoclonal IgA or IgE ≥5 g/L, or serum monoclonal IgD ≥0.5g/L; or urine M-protein of ≥200 mg/24 hr 4. Relapse or progression of myeloma following prior systemic antineoplastic therapy.
Exclusion criteria
1. Previous treatment with VELCADE 2. More than 3 previous lines of therapy (separate lines of therapy are defined as single or combination therapies that are either separated by disease progression or by a greater than 6 month treatment-free interval) 3. Peripheral neuropathy or neuropathic pain of NCI CTCAE Grade ≥2 4. Any of the following within 3 weeks prior to randomization: antineoplastic or experimental therapy, corticosteroid use above 10mg a day (prednisone or equivalent), or plasmapheresis 5. Any of the following within 2 weeks prior to randomization: radiation therapy, major surgery (kyphoplasty is not considered major surgery) 6. Prior malignancy other than multiple myeloma diagnosed or treated within the last 2 years, with the exception of completely resected carcinoma in situ or basal/squamous carcinoma of the skin
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Overall Response (Complete Response + Partial Response) | Over 4 cycles (prior to the addition of dexamethasone) | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Complete Response | Over 4 cycles (prior to the addition of dexamethasone) | 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. |
Countries
Belgium, France, Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 148 |
| 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. | 74 |
| Total | 222 |
Baseline characteristics
| Characteristic | VELCADE Subcutaneous | VELCADE Intravenous | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 74 Participants | 37 Participants | 111 Participants |
| Age, Categorical Between 18 and 65 years | 74 Participants | 37 Participants | 111 Participants |
| Age Continuous | 64.3 years STANDARD_DEVIATION 8.96 | 64.0 years STANDARD_DEVIATION 12.11 | 64.2 years STANDARD_DEVIATION 10.09 |
| Region of Enrollment Argentina | 5 participants | 8 participants | 13 participants |
| Region of Enrollment Belgium | 7 participants | 5 participants | 12 participants |
| Region of Enrollment France | 22 participants | 14 participants | 36 participants |
| Region of Enrollment Germany | 2 participants | 4 participants | 6 participants |
| Region of Enrollment India | 3 participants | 3 participants | 6 participants |
| Region of Enrollment Netherlands | 6 participants | 4 participants | 10 participants |
| Region of Enrollment Poland | 20 participants | 7 participants | 27 participants |
| Region of Enrollment Russian Federation | 26 participants | 9 participants | 35 participants |
| Region of Enrollment Ukraine | 51 participants | 17 participants | 68 participants |
| Region of Enrollment United Kingdom | 6 participants | 3 participants | 9 participants |
| Sex: Female, Male Female | 74 Participants | 27 Participants | 101 Participants |
| Sex: Female, Male Male | 74 Participants | 47 Participants | 121 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 112 / 147 | 66 / 74 |
| serious Total, serious adverse events | 53 / 147 | 26 / 74 |
Outcome results
Primary
Number of Patients With Overall Response (Complete Response + Partial Response)
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
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VELCADE Subcutaneuous | Number of Patients With Overall Response (Complete Response + Partial Response) | 61 Participants |
| VELCADE Intravenous | Number of Patients With Overall Response (Complete Response + Partial Response) | 31 Participants |
Comparison: In this trial, non-inferiority is defined as retaining 60% of the IV (active control) treatment effect as measured by ORR. The non-inferiority hypothesis can be stated as: H0: ORRSC - 0.60 ORRIV \<0 vs. H1: ORRSC - 0.60 ORRIV ≥0 (non-inferiority).p-value: 0.0020195% CI: [6.1, 27.1]Farrrington and Manning
Secondary
Number of Patients With Complete Response
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VELCADE Subcutaneuous | Number of Patients With Complete Response | 9 Participants |
| VELCADE Intravenous | Number of Patients With Complete Response | 6 Participants |