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

• ClinicalTrials.gov Identifier: NCT01734928
• Recruitment Status: Completed
• First Posted: November 28, 2012
• Results First Posted: June 6, 2023
• Last Update Posted: June 6, 2023
• Sponsor: Celgene
• Information provided by (Responsible Party): Celgene

Tracking Information

• First Submitted Date: November 23, 2012
• First Posted Date: November 28, 2012
• Results First Submitted Date: May 9, 2023
• Results First Posted Date: June 6, 2023
• Last Update Posted Date: June 6, 2023
• Actual Study Start Date: January 7, 2013
• Actual Primary Completion Date: May 9, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 5, 2023)

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.

Original Primary Outcome Measures (submitted: November 27, 2012)

Progression Free Survival [ Time Frame: Up to 1 year ]

The length of time during and after the treatment that participants in the study live without the disease getting worse

Current Secondary Outcome Measures (submitted: June 5, 2023)

• 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.

Original Secondary Outcome Measures (submitted: November 27, 2012)

• Overall Survival [ Time Frame: Up to 5 years ]
  The length of time from start of study treatment that participants in the study are alive
• Adverse Event [ Time Frame: Up to 1 year ]
  Number of participants with adverse events
• Overall Response Rate [ Time Frame: Up to 1 year ]
  The percentage of participants who respond to study treatment
• Duration of Response [ Time Frame: Up to 1 year ]
  The length of time from when participants respond to the study treatment to when their disease gets worse

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety and Efficacy of Pomalidomide, Bortezomib and Low-dose Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma
• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Multiple Myeloma

Intervention

• Drug: Pomalidomide
  Pomalidomide 4 mg will be taken orally on Days 1-14 of a 21-day cycle.
  Other Names:

  • Oral Pomalidomide
  • CC-4047
• 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.

Study Arms

• 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.
  Interventions:

  • Drug: Pomalidomide
  • Drug: Bortezomib
  • Drug: Dexamethasone
• 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.
  Interventions:

  • Drug: Bortezomib
  • Drug: Dexamethasone

Publications *

• Richardson PG, Oriol A, Beksac M, Liberati AM, Galli M, Schjesvold F, Lindsay J, Weisel K, White D, Facon T, San Miguel J, Sunami K, O'Gorman P, Sonneveld P, Robak P, Semochkin S, Schey S, Yu X, Doerr T, Bensmaine A, Biyukov T, Peluso T, Zaki M, Anderson K, Dimopoulos M; OPTIMISMM trial investigators. Pomalidomide, bortezomib, and dexamethasone for patients with relapsed or refractory multiple myeloma previously treated with lenalidomide (OPTIMISMM): a randomised, open-label, phase 3 trial. Lancet Oncol. 2019 Jun;20(6):781-794. doi: 10.1016/S1470-2045(19)30152-4. Epub 2019 May 13.
• Richardson PG, Hofmeister CC, Raje NS, Siegel DS, Lonial S, Laubach J, Efebera YA, Vesole DH, Nooka AK, Rosenblatt J, Doss D, Zaki MH, Bensmaine A, Herring J, Li Y, Watkins L, Chen MS, Anderson KC. Pomalidomide, bortezomib and low-dose dexamethasone in lenalidomide-refractory and proteasome inhibitor-exposed myeloma. Leukemia. 2017 Dec;31(12):2695-2701. doi: 10.1038/leu.2017.173. Epub 2017 Jun 2. Erratum In: Leukemia. 2018 Oct;32(10):2305.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 25, 2017): 559
• Original Estimated Enrollment (submitted: November 27, 2012): 782
• Actual Study Completion Date: May 13, 2022
• Actual Primary Completion Date: May 9, 2022 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Austria, Canada, Denmark, Finland, France, Germany, Greece, Ireland, Israel, Italy, Japan, Netherlands, Norway, Poland, Portugal, Puerto Rico, Russian Federation, Spain, Sweden, Turkey, United Kingdom, United States
• Removed Location Countries: Argentina, Australia

Administrative Information

• NCT Number: NCT01734928
• Other Study ID Numbers: CC-4047-MM-007
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Celgene
• Original Responsible Party: Celgene Corporation
• Current Study Sponsor: Celgene
• Original Study Sponsor: Celgene Corporation
• Collaborators: Not Provided

Investigators

• Study Director: Bristol Myers-Squibb; Bristol-Myers Squibb
• Study Director: Amine Bensmaine, MD; Celgene Corporation

• PRS Account: Celgene
• Verification Date: May 2023