Safety and Efficacy of Pomalidomide, Bortezomib and Low-dose Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma (OPTIMISMM)
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| ClinicalTrials.gov Identifier: NCT01734928 |
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Recruitment Status :
Completed
First Posted : November 28, 2012
Results First Posted : June 6, 2023
Last Update Posted : June 6, 2023
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Multiple Myeloma | Drug: Pomalidomide Drug: Bortezomib Drug: Dexamethasone | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 559 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | January 7, 2013 |
| Actual Primary Completion Date : | May 9, 2022 |
| Actual Study Completion Date : | May 13, 2022 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Pomalidomide, Bortezomib and Low Dose Dexamethasone
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.
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Drug: Pomalidomide
Pomalidomide 4 mg will be taken orally on Days 1-14 of a 21-day cycle.
Other Names:
Drug: Bortezomib 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.
Other Name: Velcade Drug: Dexamethasone 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. |
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Active Comparator: Bortezomib and Low Dose Dexamethasone
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.
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Drug: Bortezomib
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.
Other Name: Velcade Drug: Dexamethasone 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. |
- Progression Free Survival by Independent Response Adjudication Committee (IRAC) [ Time Frame: From randomization to progressive disease or death during the IRAC assessment period, up to approximately 42 months ]
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.
- Overall Survival (OS) [ Time Frame: From randomization to date of death, up to approximately 65 months ]Overall survival (OS) is calculated as the time from randomization to death from any cause.
- Overall Response Rate by Independent Response Adjudication Committee (IRAC) [ Time Frame: From randomization to progressive disease or death during the IRAC assessment period, up to approximately 42 months ]
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
- Duration of Response by Independent Response Adjudication Committee (IRAC) [ Time Frame: From randomization to progressive disease or death during the IRAC assessment period, up to approximately 42 months ]
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
- Number of Participants With Grade 3-4 Treatment Emergent Adverse Events (TEAE) [ Time Frame: From first dose to 28 days after the last dose (up to approximately 44 months ]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.
- Number of Participants With Grade 5 Treatment Emergent Adverse Events (TEAE) [ Time Frame: From first dose to 28 days after the last dose (up to approximately 44 months ]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.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01734928
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| Study Director: | Bristol Myers-Squibb | Bristol-Myers Squibb | |
| Study Director: | Amine Bensmaine, MD | Celgene Corporation |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Celgene |
| ClinicalTrials.gov Identifier: | NCT01734928 |
| Other Study ID Numbers: |
CC-4047-MM-007 |
| First Posted: | November 28, 2012 Key Record Dates |
| Results First Posted: | June 6, 2023 |
| Last Update Posted: | June 6, 2023 |
| Last Verified: | May 2023 |
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Multiple Myeloma Pomalidomide |
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Multiple Myeloma Neoplasms, Plasma Cell Neoplasms by Histologic Type Neoplasms Hemostatic Disorders Vascular Diseases Cardiovascular Diseases Paraproteinemias Blood Protein Disorders Hematologic Diseases Hemorrhagic Disorders Lymphoproliferative Disorders Immunoproliferative Disorders Immune System Diseases Thalidomide |
Dexamethasone Bortezomib Pomalidomide Anti-Inflammatory Agents Antiemetics Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs Gastrointestinal Agents Glucocorticoids Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Antineoplastic Agents, Hormonal Antineoplastic Agents Immunologic Factors |