Brief Summary
The purpose of this study is to compare the efficacy of the combination of pomalidomide, bortezomib and low dose dexamethasone to the combination of bortezomib and low dose dexamethasone in participants with relapsed/refractory multiple myeloma. This study will also assess how safe the combination of pomalidomide, bortezomib and low dose dexamethasone is compared to the combination of bortezomib and low dose dexamethasone.
Brief Title
Safety and Efficacy of Pomalidomide, Bortezomib and Low-dose Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma
Categories
Completion Date
Completion Date Type
Actual
Conditions
Multiple Myeloma
Eligibility Criteria
Inclusion Criteria:
* Must be ≥ 18 years at the time of signing informed consent.
* Must have documented diagnosis of multiple myeloma and have measureable disease by serum and urine protein electrophoresis.
* Must have had at least 1 but no greater than 3 prior anti-myeloma regimens.
* Must have documented disease progression during or after their last anti-myeloma therapy.
* All subjects must have received prior treatment with a lenalidomide containing regimen for at least 2 consecutive cycles.
Exclusion Criteria:
* Documented progressive disease during therapy or within 60 days of the last dose of a bortezomib-containing therapy under the 1.3 mg/m\^2 dose twice weekly dosing schedule.
* Peripheral neuropathy Grade 3, Grade 4 or Grade 2 with pain within 14 days prior to randomization.
* Non-secretory multiple myeloma.
* Subjects with severe renal impairment requiring dialysis.
* Previous therapy with pomalidomide.
* Must be ≥ 18 years at the time of signing informed consent.
* Must have documented diagnosis of multiple myeloma and have measureable disease by serum and urine protein electrophoresis.
* Must have had at least 1 but no greater than 3 prior anti-myeloma regimens.
* Must have documented disease progression during or after their last anti-myeloma therapy.
* All subjects must have received prior treatment with a lenalidomide containing regimen for at least 2 consecutive cycles.
Exclusion Criteria:
* Documented progressive disease during therapy or within 60 days of the last dose of a bortezomib-containing therapy under the 1.3 mg/m\^2 dose twice weekly dosing schedule.
* Peripheral neuropathy Grade 3, Grade 4 or Grade 2 with pain within 14 days prior to randomization.
* Non-secretory multiple myeloma.
* Subjects with severe renal impairment requiring dialysis.
* Previous therapy with pomalidomide.
Inclusion Criteria
Inclusion Criteria:
* Must be ≥ 18 years at the time of signing informed consent.
* Must have documented diagnosis of multiple myeloma and have measureable disease by serum and urine protein electrophoresis.
* Must have had at least 1 but no greater than 3 prior anti-myeloma regimens.
* Must have documented disease progression during or after their last anti-myeloma therapy.
* All subjects must have received prior treatment with a lenalidomide containing regimen for at least 2 consecutive cycles.
* Must be ≥ 18 years at the time of signing informed consent.
* Must have documented diagnosis of multiple myeloma and have measureable disease by serum and urine protein electrophoresis.
* Must have had at least 1 but no greater than 3 prior anti-myeloma regimens.
* Must have documented disease progression during or after their last anti-myeloma therapy.
* All subjects must have received prior treatment with a lenalidomide containing regimen for at least 2 consecutive cycles.
Gender
All
Gender Based
false
Keywords
Multiple Myeloma
Pomalidomide
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT01734928
Org Class
Industry
Org Full Name
Celgene
Org Study Id
CC-4047-MM-007
Overall Status
Completed
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase 3, Multicenter, Randomized, Open-Label Study to Compare the Efficacy and Safety of Pomalidomide, Bortezomib and Low-Dose Dexamethasone Versus Bortezomib and Low-Dose Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma
Primary Outcomes
Outcome Description
Progression free survival (PFS) will be calculated as the time between the randomization and progressive disease (PD) or death.
Progressive Disease is defined as an Increase of ≥ 25% from nadir in:
* Serum M-component and/or (the absolute increase must be ≥ 0.5 g/dL)g
* Urine M-component and/or (the absolute increase must be ≥ 200 mg/24 hours)
* In patients without measurable serum and urine M-protein levels the difference between involved and uninvolved FLC levels, the absolute increase must be \> 100 mg/dL.
* Bone marrow plasma cell percentage, the absolute % must be ≥ 10%h
* Definite development of new bone lesions or soft tissue plasmacytomas increase in the size of existing bone lesions or soft tissue plasmacytomas. -Development of hypercalcemia (corrected serum calcium \> 11.5 mg/dL or 2.65 mmol/L) that can be attributed solely to the plasma cell proliferative disorder.
Progressive Disease is defined as an Increase of ≥ 25% from nadir in:
* Serum M-component and/or (the absolute increase must be ≥ 0.5 g/dL)g
* Urine M-component and/or (the absolute increase must be ≥ 200 mg/24 hours)
* In patients without measurable serum and urine M-protein levels the difference between involved and uninvolved FLC levels, the absolute increase must be \> 100 mg/dL.
* Bone marrow plasma cell percentage, the absolute % must be ≥ 10%h
* Definite development of new bone lesions or soft tissue plasmacytomas increase in the size of existing bone lesions or soft tissue plasmacytomas. -Development of hypercalcemia (corrected serum calcium \> 11.5 mg/dL or 2.65 mmol/L) that can be attributed solely to the plasma cell proliferative disorder.
Outcome Measure
Progression Free Survival by Independent Response Adjudication Committee (IRAC)
Outcome Time Frame
From randomization to progressive disease or death during the IRAC assessment period, up to approximately 42 months
Secondary Outcomes
Outcome Description
Overall survival (OS) is calculated as the time from randomization to death from any cause.
Outcome Time Frame
From randomization to date of death, up to approximately 65 months
Outcome Measure
Overall Survival (OS)
Outcome Description
The ORR together with the relative proportions in each response category (ie, stringent CR \[sCR\], CR, very good PR \[VGPR\], PR, SD, and PD) by treatment using the IMWG criteria will be examined.
Complete Response: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow
SCR: CR+ Normal FLC ratio and Absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence
VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine Mprotein level \< 100 mg per 24 hours
PR: ≥ 50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by ≥ 90% or to \< 200 mg per 24 hours
Progressive Disease: Please refer to Primary outcome measure for definition
SD: Not meeting criteria for CR, VGPR, PR, or progressive disease
Complete Response: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow
SCR: CR+ Normal FLC ratio and Absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence
VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine Mprotein level \< 100 mg per 24 hours
PR: ≥ 50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by ≥ 90% or to \< 200 mg per 24 hours
Progressive Disease: Please refer to Primary outcome measure for definition
SD: Not meeting criteria for CR, VGPR, PR, or progressive disease
Outcome Time Frame
From randomization to progressive disease or death during the IRAC assessment period, up to approximately 42 months
Outcome Measure
Overall Response Rate by Independent Response Adjudication Committee (IRAC)
Outcome Description
Duration of myeloma response is defined as the duration from the time when the IMWG response criteria are first met for sCR or CR or VGPR or PR until the first date the response criteria are met for PD or until the subject died from any cause, whichever occurs first.
Complete Response: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow
SCR: CR+ Normal FLC ratio and Absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence
VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine Mprotein level \< 100 mg per 24 hours
PR: ≥ 50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by ≥ 90% or to \< 200 mg per 24 hours
Progressive Disease: Please refer to Primary outcome measure for definition
SD: Not meeting criteria for CR, VGPR, PR, or progressive disease
Complete Response: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow
SCR: CR+ Normal FLC ratio and Absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence
VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine Mprotein level \< 100 mg per 24 hours
PR: ≥ 50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by ≥ 90% or to \< 200 mg per 24 hours
Progressive Disease: Please refer to Primary outcome measure for definition
SD: Not meeting criteria for CR, VGPR, PR, or progressive disease
Outcome Time Frame
From randomization to progressive disease or death during the IRAC assessment period, up to approximately 42 months
Outcome Measure
Duration of Response by Independent Response Adjudication Committee (IRAC)
Outcome Description
Treatment-emergent adverse events (TEAEs) are defined as any AE occurring or worsening on or after the first dose date of the study treatment and within 28 days after the last dose date.
Outcome Time Frame
From first dose to 28 days after the last dose (up to approximately 44 months
Outcome Measure
Number of Participants With Grade 3-4 Treatment Emergent Adverse Events (TEAE)
Outcome Description
Treatment-emergent adverse events (TEAEs) are defined as any AE occurring or worsening on or after the first dose date of the study treatment and within 28 days after the last dose date.
Outcome Time Frame
From first dose to 28 days after the last dose (up to approximately 44 months
Outcome Measure
Number of Participants With Grade 5 Treatment Emergent Adverse Events (TEAE)
See Also Links
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Amit Verma
Investigator Email
amit.verma@einsteinmed.org
Investigator Phone
718-405-8505 / 718-904-2900