Safety and Efficacy of Pomalidomide, Bortezomib and Low-dose Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: Pomalidomide
* Drug: Bortezomib
* Drug: Dexamethasone


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pomalidomide, Bortezomib and Low Dose Dexamethasone<br>4 mg of Pomalidomide will be taken orally on Days 1-14 of a 21-day cycle along with 1.3 mg/m2 of Bortezomib administered subcutaneously on Days 1, 4, 8 and 11 of 21 days for cycles 1 -8 and on days 1, 8 of 21 days for cycle 9 and onward until disease progression, and Dexamethasone 20 mg/day [≤ 75 years old] or 10 mg/day [> 75 years old] orally on days 1, 2, 4, 5, 8, 9, 11, 12 of 21 days for cycles 1-8 and on days 1, 2,8, 9 of 21 days for cycles 9 and onward until disease progression. | Drug: Pomalidomide<br>* Pomalidomide 4 mg will be taken orally on Days 1-14 of a 21-day cycle.<br>* Other names: CC-4047;Drug: Bortezomib<br>* Bortezomib 1.3 mg/m2 will be administered subcutaneously on Days 1, 4, 8 and 11 of 21 days for cycles 1 -8 and on Days 1, 8 of 21 days for cycle 9 and onward until disease progression.<br>* Other names: Velcade;Drug: Dexamethasone<br>* Dexamethasone 20 mg/day [≤ 75 years old] or 10 mg/day [>75 years old] will be taken orally on Days 1, 2, 4, 5, 8, 9, 11, 12 of 21 days for cycles 1-8 and on Days 1, 2, 8, 9 of 21 days for cycles 9 and onward until disease progression.<br>|
| Active Comparator: Bortezomib and Low Dose Dexamethasone<br>1.3 mg/m2 of Bortezomib will be administered subcutaneously on Days 1, 4, 8 and 11 of 21 days for cycles 1 -8 and on Days 1, 8 of 21 days for cycle 9 and onward until disease progression along with Dexamethasone 20 mg/day [≤ 75 years old]or 10 mg/day [> 75 years old] orally on days 1, 2, 4, 5, 8, 9, 11, 12 of 21 days for cycles 1-8 and on Days 1, 2, 8, 9 of 21 days for cycles 9 and onward until disease progression. | Drug: Bortezomib<br>* Bortezomib 1.3 mg/m2 will be administered subcutaneously on Days 1, 4, 8 and 11 of 21 days for cycles 1 -8 and on Days 1, 8 of 21 days for cycle 9 and onward until disease progression.<br>* Other names: Velcade;Drug: Dexamethasone<br>* Dexamethasone 20 mg/day [≤ 75 years old] or 10 mg/day [>75 years old] will be taken orally on Days 1, 2, 4, 5, 8, 9, 11, 12 of 21 days for cycles 1-8 and on Days 1, 2, 8, 9 of 21 days for cycles 9 and onward until disease progression.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival by Independent Response Adjudication Committee (IRAC) | 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. | From randomization to progressive disease or death during the IRAC assessment period, up to approximately 42 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | Overall survival (OS) is calculated as the time from randomization to death from any cause. | From randomization to date of death, up to approximately 65 months | 
| Overall Response Rate by Independent Response Adjudication Committee (IRAC) | 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 | From randomization to progressive disease or death during the IRAC assessment period, up to approximately 42 months | 
| Duration of Response by Independent Response Adjudication Committee (IRAC) | 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 | From randomization to progressive disease or death during the IRAC assessment period, up to approximately 42 months | 
| Number of Participants With Grade 3-4 Treatment Emergent Adverse Events (TEAE) | 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. | From first dose to 28 days after the last dose (up to approximately 44 months | 
| Number of Participants With Grade 5 Treatment Emergent Adverse Events (TEAE) | 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. | From first dose to 28 days after the last dose (up to approximately 44 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Myeloma, Pomalidomide