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NCT03110562: BOSTON

Bortezomib, Selinexor, and Dexamethasone in Patients With Multiple Myeloma

Completed Phase 3 Results posted Last updated 21 August 2024
What this trial tests

Phase 3 trial testing Selinexor in Multiple Myeloma in 402 participants. Completed in 12 May 2022.

Timeline
24 May 2017
Primary endpoint
18 February 2020
12 May 2022

Quick facts

Lead sponsorKaryopharm Therapeutics Inc
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment402
Start date24 May 2017
Primary completion18 February 2020
Estimated completion12 May 2022
Sites157 locations across Italy, Poland, Russia, Belgium, Bulgaria, Czechia, United States, France

Drugs / interventions tested

Conditions studied

Sponsor

Karyopharm Therapeutics Inc — full company profile →

Who can join

18 and older, any sex, with Multiple Myeloma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

SVd/Vd Arm: Progression-free Survival (PFS) as Assessed by Independent Review Committee (IRC) Primary · From date of randomization until IRC-confirmed documented PD or death, censored date, whichever occurred first (up to 33 months)

PFS was defined as time from date of randomization until the first date of IRC-confirmed PD, per International Myeloma Working Group (IMWG) response criteria, or death due to any cause, whichever occurs first. PD included increase of 25% from lowest confirmed response value in 1 or more of the following criteria: a) serum M-protein with absolute increase of \>= 0.5 gram per deciliter (g/dL); b) serum M-protein increase \>= 1 g/dL if the lowest M-component was \>=5 g/dL; c) urine M-protein (absolute increase must be \>= 200 mg per 24 hours); d) in participants without measurable serum and urine

GroupValue95% CI
SVd Arm: Selinexor + Bortezomib + Dexamethasone13.9311.73 – NA
Vd Arm: Bortezomib + Dexamethasone9.468.11 – 10.78
SVd/Vd Arm: Overall Response Rate (ORR) as Assessed by IRC Secondary · From date of randomization until disease progression or initiating a new MM treatment (up to 33 months)

ORR was defined as the percentage of the participants who achieved any confirmed partial response (PR) or better PR, complete response (CR), very good partial response (VGPR) or stringent complete response (sCR) based on the IRC's response outcome assessments, according to the International Myeloma Working Group (IMWG) response criteria, before IRC-confirmed PD or initiating a new MM treatment. PR: \>= 50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by \>= 90% or to \< 200 mg per 24 hours; VGPR: Serum and urine M-protein detectable by immunofixation but not on elect

GroupValue95% CI
SVd Arm: Selinexor + Bortezomib + Dexamethasone76.469.8 – 82.2
Vd Arm: Bortezomib + Dexamethasone62.355.3 – 68.9
SVd/Vd Arm: Percentage of Participants With Response Rate of Very Good Partial Response (VGPR) or Better Based on IRC Assessment Secondary · From date of randomization until confirmed PD or initiating a new MM treatment (up to 33 months)

Response rate was defined as percentage of participants with responses of VGPR, at any time prior to IRC-confirmed PD or initiating a new MM treatment. VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level \< 100 mg per 24 hours.

GroupValue95% CI
SVd Arm: Selinexor + Bortezomib + Dexamethasone44.637.5 – 51.9
Vd Arm: Bortezomib + Dexamethasone32.426.0 – 39.2
SVd/Vd Arm: Number of Participants With at Least One Grade Greater Than or Equal to [>=] 2 Peripheral Neuropathy Events Secondary · From first dose of study treatment to 30 days after the last dose of study treatment inclusive, or the day before the start of new anti-MM treatment, whichever occurs first (up to 33 months)

Peripheral neuropathy events was assessed using the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03. The grade ranges from Grade 1 (mild, asymptomatic, or mild symptoms) to Grade 5 (death related to an adverse event). Grade 2 indicates a moderate condition that may require minimal intervention and can limit certain daily activities. Grade 3 represents severe symptoms that are not immediately life-threatening but may lead to hospitalization and restrict self-care activities. Grade 4 denotes life-threatening consequences requiring urgent interven

GroupValue95% CI
SVd Arm: Selinexor + Bortezomib + Dexamethasone41
Vd Arm: Bortezomib + Dexamethasone70
SVd/Vd Arm: Overall Survival (OS) Secondary · From date of randomization to the date of death or censored date, whichever occurred first (up to 45 months)

OS was defined as the time from the date of randomization until either the date of death due to any cause or until the participant is lost to follow-up, for all participants.

GroupValue95% CI
SVd Arm: Selinexor + Bortezomib + Dexamethasone36.6730.19 – NA
Vd Arm: Bortezomib + Dexamethasone32.7627.83 – NA
SVd/Vd Arm: Duration of Response (DOR) as Assessed by IRC Secondary · From the first documentation of response to the first documentation of PD or death, whichever occurred first (up to 45 months)

DOR was defined as the duration of time from the first occurrence of an IRC confirmed response of at least (\>=) PR until the first date of IRC-confirmed PD or death due to any cause, whichever occurred first. PR: \>= 50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by \>= 90% or to \< 200 mg per 24 hours; PD: Increase of 25% from lowest confirmed response value in 1 or more of the following criteria: Serum M-protein with absolute increase of \>= 0.5 g/dL; Serum M-protein increase \>= 1 g/dL if the lowest M-component was \>= 5 g/dL; Urine M-protein (absolute increase

GroupValue95% CI
SVd Arm: Selinexor + Bortezomib + Dexamethasone17.2812.55 – 26.25
Vd Arm: Bortezomib + Dexamethasone12.889.26 – 15.77
SVdX Arm: Overall Response Rate (ORR1) as Assessed by IRC During SVdX Treatment Secondary · From date of first SVdX treatment until disease progression or initiating a new MM treatment (up to 33 months)

ORR was defined as the percentage of the participants who achieved a confirmed partial response or better (i.e., PR, VGPR, CR, or sCR) based on the IRC's response outcome assessments, according to the IMWG response criteria. PR: \>=50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by \>=90% or \<200 mg per 24 hours; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level \<100 mg per 24 hours; CR: Negative immunofixation on the serum and urine and disappearance of

GroupValue95% CI
SVdX Arm: Selinexor + Bortezomib + Dexamethasone19.010.2 – 30.9
SVdX Arm: Progression Free Survival1 (PFS1) as Assessed by IRC During SVdX Treatment Secondary · From date of first SVdX treatment until IRC-confirmed documented PD or death or censored date, whichever occurred first (up to 33 months)

PFS1 is defined as the duration of time from the date of the first dose of the SVd treatment after crossover from the Vd arm until the first date of PD or death due to any cause, whichever occurred first. PD included increase of 25% from lowest confirmed response value in 1 or more of the following criteria: a) serum M-protein with absolute increase of \>= 0.5 gram per deciliter (g/dL); b) serum M-protein increase \>= 1 g/dL if the lowest M-component was \>=5 g/dL; c) urine M-protein (absolute increase must be \>= 200 mg per 24 hours); d) in participants without measurable serum and urine M-pr

GroupValue95% CI
SVdX Arm: Selinexor + Bortezomib + Dexamethasone3.913.48 – 6.93
SVd/Vd Arm: Time-to-next-treatment (TTNT) in Participants Randomized to the SVd and Vd Arm Who Received Treatment After SVd/Vd Secondary · From date of randomization to start of next anti-MM treatment or death, whichever occurred first (up to 33 months)

TTNT is defined as the duration from date of randomization to start of next anti-MM treatment or death, whichever occurs first. For patients without an event, their follow-up time will be censored at the date of discontinuation from study, or last participating visit on or before database cutoff date, whichever occurs first.

GroupValue95% CI
SVd Arm: Selinexor + Bortezomib + Dexamethasone16.1313.93 – NA
Vd Arm: Bortezomib + Dexamethasone10.849.82 – 13.40
SVd/Vd Arm: Time To Response (TTR) in Participants Randomized to the SVd and Vd Arm Secondary · From randomization to the date of first IRC-confirmed PR or better (i.e., PR, VGPR, CR, or sCR), whichever occurred first (up to 33 months)

TTR was defined as duration from randomization to the date of first IRC-confirmed PR or better (i.e., PR, VGPR, CR, or sCR) before IRC-confirmed PD or initiating a new MM treatment per IMWG response criteria. The participants who do not achieve IRC-confirmed PR or better response will be censored at the date of last disease assessment on or before database cutoff date. PR: \>= 50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by \>= 90% or to \< 200 mg per 24 hours; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or great

GroupValue95% CI
SVd Arm: Selinexor + Bortezomib + Dexamethasone1.411.35 – 1.51
Vd Arm: Bortezomib + Dexamethasone1.611.51 – 2.14
SVd/Vd/SVdx Arm: Progression Free Survival 2 (PFS 2) in Participants Randomized to the SVd and Vd Arm Who Received Post-SVd/Vd/SVdX Treatment Secondary · From date of first dose of post-SVd/Vd/SVdX treatment to the date of first PD on post-SVd/Vd/SVdX treatment, or death due to any cause (up to 33 months)

PFS 2 was defined as the duration of time from the date of the first dose of the treatment after SVd/Vd/SVdX until the first date of PD on treatment after SVd/Vd/SVdX or death due to any cause, whichever occurred first. PD included increase of 25% from lowest confirmed response value in 1 or more of the following criteria: a) serum M-protein with absolute increase of \>= 0.5 gram per deciliter (g/dL); b) serum M-protein increase \>= 1 g/dL if the lowest M-component was \>=5 g/dL; c) urine M-protein (absolute increase must be \>= 200 mg per 24 hours); d) in participants without measurable serum

GroupValue95% CI
SVd Arm: Selinexor + Bortezomib + Dexamethasone6.605.39 – 9.43
Vd Arm (Non-Crossover): Bortezomib + Dexamethasone8.845.78 – NA
SVdX Arm: Selinexor + Bortezomib + Dexamethasone3.882.79 – NA
SVd/Vd Arm: Change From Baseline in Participant-Reported Peripheral Neuropathy (PN) Assessed by European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire- Chemotherapy-Induced PN 20 (EORTC- QLQ-CIPN20) Total Scores Secondary · Svd Arm: Baseline up to End of treatment (EOT) (at Day 820); Vd Arm: Baseline up to EOT (at Day 848)

The EORTC QLQ-CIPN20 instrument is a 20-item QoL instrument, which has been developed to elicit patients' experience of symptoms and functional limitations related to CIPN. The QLQ-CIPN20 contains 20 items assessing sensory (9 items), motor (8 items), and autonomic symptoms (3 items) containing a 4-point Likert scale (1= not at all, 2= a little, 3= quite a bit, and 4= very much), participants indicate the degree to which they have experienced sensory, motor, and autonomic symptoms during the past week. Sensory raw scale scores range from 1 to 36, motor raw scale scores range from 1 to 32, and

Total Sensory Score: Change at EOT
GroupValue95% CI
SVd Arm: Selinexor + Bortezomib + Dexamethasone3.38± 12.436
Vd Arm: Bortezomib + Dexamethasone11.17± 19.069
Total Motor Score: Change at EOT
GroupValue95% CI
SVd Arm: Selinexor + Bortezomib + Dexamethasone3.56± 14.513
Vd Arm: Bortezomib + Dexamethasone9.02± 18.662
Total Autonomic Score: Change at EOT
GroupValue95% CI
SVd Arm: Selinexor + Bortezomib + Dexamethasone10.41± 22.201
Vd Arm: Bortezomib + Dexamethasone10.92± 25.306

Adverse events — posted to ClinicalTrials.gov

Time frame: From date of randomization up to 45 months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

SVd Arm: Selinexor + Bortezomib + Dexamethasone
Serious: 109/195 (56%)
Deaths: 74/195
Vd Arm: Bortezomib + Dexamethasone
Serious: 79/204 (39%)
Deaths: 82/204
SVdX Arm: Selinexor + Bortezomib + Dexamethasone
Serious: 28/66 (42%)
Deaths: 37/66
SdX Arm: Selinexor + Dexamethasone
Serious: 7/14 (50%)
Deaths: 3/14

Serious adverse events (170 terms)

ReactionSystemSVd Arm: Selinexor + Borte…Vd Arm: Bortezomib + Dexam…SVdX Arm: Selinexor + Bort…SdX Arm: Selinexor + Dexam…
PneumoniaInfections and infestations
CataractEye disorders
AnaemiaBlood and lymphatic system disorders
DiarrhoeaGastrointestinal disorders
VomitingGastrointestinal disorders
ThrombocytopeniaBlood and lymphatic system disorders
Atrial fibrillationCardiac disorders
NauseaGastrointestinal disorders
Lower respiratory tract infectionInfections and infestations
GastroenteritisInfections and infestations
Septic shockInfections and infestations
Urinary tract infectionInfections and infestations
Acute kidney injuryRenal and urinary disorders
PyrexiaGeneral disorders
General physical health deteriorationGeneral disorders
BronchitisInfections and infestations
InfluenzaInfections and infestations
Upper respiratory tract infectionInfections and infestations
UrosepsisInfections and infestations
DehydrationMetabolism and nutrition disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
Febrile neutropeniaBlood and lymphatic system disorders
ConstipationGastrointestinal disorders
Abdominal painGastrointestinal disorders
Other adverse events (82 terms — click to expand)

ReactionSystemSVd Arm: Selinexor + Borte…Vd Arm: Bortezomib + Dexam…SVdX Arm: Selinexor + Bort…SdX Arm: Selinexor + Dexam…
ThrombocytopeniaBlood and lymphatic system disorders
Neuropathy peripheralNervous system disorders
NauseaGastrointestinal disorders
FatigueGeneral disorders
AnaemiaBlood and lymphatic system disorders
Decreased appetiteMetabolism and nutrition disorders
DiarrhoeaGastrointestinal disorders
Weight decreasedInvestigations
AstheniaGeneral disorders
CataractEye disorders
VomitingGastrointestinal disorders
Upper respiratory tract infectionInfections and infestations
CoughRespiratory, thoracic and mediastinal disorders
ConstipationGastrointestinal disorders
InsomniaPsychiatric disorders
NeutropeniaBlood and lymphatic system disorders
Back painMusculoskeletal and connective tissue disorders
Oedema peripheralGeneral disorders
PyrexiaGeneral disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
DizzinessNervous system disorders
NasopharyngitisInfections and infestations
BronchitisInfections and infestations
ArthralgiaMusculoskeletal and connective tissue disorders
HeadacheNervous system disorders
HypokalaemiaMetabolism and nutrition disorders
HypophosphataemiaMetabolism and nutrition disorders
Pain in extremityMusculoskeletal and connective tissue disorders
HypertensionVascular disorders
PneumoniaInfections and infestations
Confusional statePsychiatric disorders
Abdominal painGastrointestinal disorders
HypocalcaemiaMetabolism and nutrition disorders
HyponatraemiaMetabolism and nutrition disorders
ParaesthesiaNervous system disorders
Visual impairmentEye disorders
HyperglycaemiaMetabolism and nutrition disorders
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
Vision blurredEye disorders

Most-reported serious reactions: Pneumonia, Cataract, Anaemia, Diarrhoea, Vomiting, Thrombocytopenia, Atrial fibrillation, Nausea.

Data from ClinicalTrials.gov NCT03110562 adverse events section.

Sponsor's own description

This Phase 3, 2-arm, randomized, active comparator-controlled, open-label, multicenter study will compare the efficacy and health-related quality of life (HR-QoL) and assess the safety of selinexor plus bortezomib (Velcade) plus low-dose dexamethasone (SVd) versus bortezomib plus low-dose dexamethasone (Vd) in adult patients with RRMM who have received 1 to 3 prior anti-multiple myeloma (MM) regimens. Crossover from the Vd Arm to a treatment that includes selinexor (i.e., SVdX or SdX) will be allowed at the point of IRC-confirmed objective disease progression per the IMWG criteria for patients in the Vd Arm.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Once-per-week selinexor, bortezomib, and dexamethasone versus twice-per-week bortezomib and dexamethasone in patients with multiple myeloma (BOSTON): a randomised, open-label, phase 3 trial.
    Grosicki S, Simonova M, Spicka I, Pour L, et al · · 2020 · cited 236× · PMID 33189178 · DOI 10.1016/s0140-6736(20)32292-3
  2. XPO1-dependent nuclear export as a target for cancer therapy.
    Azizian NG, Li Y. · · 2020 · cited 183× · PMID 32487143 · DOI 10.1186/s13045-020-00903-4
  3. Understanding and targeting resistance mechanisms in cancer.
    Lei ZN, Tian Q, Teng QX, Wurpel JND, et al · · 2023 · cited 174× · PMID 37229486 · DOI 10.1002/mco2.265
  4. Small Molecule NF-κB Pathway Inhibitors in Clinic.
    Ramadass V, Vaiyapuri T, Tergaonkar V. · · 2020 · cited 154× · PMID 32708302 · DOI 10.3390/ijms21145164
  5. Selective Inhibition of Nuclear Export With Oral Selinexor for Treatment of Relapsed or Refractory Multiple Myeloma.
    Vogl DT, Dingli D, Cornell RF, Huff CA, et al · · 2018 · cited 125× · PMID 29381435 · DOI 10.1200/jco.2017.75.5207
  6. Bortezomib for the Treatment of Hematologic Malignancies: 15 Years Later.
    Robak P, Robak T. · · 2019 · cited 103× · PMID 30993606 · DOI 10.1007/s40268-019-0269-9
  7. Selinexor plus low-dose bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma.
    Bahlis NJ, Sutherland H, White D, Sebag M, et al · · 2018 · cited 103× · PMID 30352784 · DOI 10.1182/blood-2018-06-858852
  8. The past, present, and future of CRM1/XPO1 inhibitors.
    Wang AY, Liu H. · · 2019 · cited 85× · PMID 30976603 · DOI 10.21037/sci.2019.02.03

Verify or expand the search:

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Trials by the same sponsor.

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