BOSTON: Bortezomib, Selinexor, and Dexamethasone in Patients With Multiple Myeloma

Sponsor
Karyopharm Therapeutics Inc (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03110562
Collaborator
(none)
402
Enrollment
157
Locations
2
Arms
75.3
Anticipated Duration (Months)
2.6
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or DiseaseIntervention/TreatmentPhase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
402 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 3 Randomized, Controlled, Open-label Study of Selinexor, Bortezomib, and Dexamethasone (SVd) Versus Bortezomib and Dexamethasone (Vd) in Patients With Relapsed or Refractory Multiple Myeloma (RRMM)
Actual Study Start Date :
May 24, 2017
Actual Primary Completion Date :
Feb 18, 2020
Anticipated Study Completion Date :
Sep 1, 2023

Arms and Interventions

ArmIntervention/Treatment
Active Comparator: selinexor+bortezomib+dexamethasone (SVd)

Selinexor will be given on Days 1, 8, 15, 22, and 29 of each 35-day cycle. Bortezomib will be given Days 1, 8, 15, and 22 of each 35-day cycle. Dexamethasone will be given Days 1, 2, 8, 9, 15, 16, 22, 23, 29, and 30 of each 35-day cycle.

Drug: Selinexor
oral 100 mg dose

Drug: Bortezomib
subcutaneous dose of 1.3 mg/m2
Other Names:
  • Velcade®
  • Drug: Dexamethasone
    oral dose of 20mg

    Active Comparator: bortezomib+dexamethasone (Vd)

    Bortezomib will be given Days 1, 4, 8, and 11 of each 21-day cycle for the first 8 cycles. For cycles ≥ 9, bortezomib will be given on Days 1, 8, 15, and 22 of each 35-day cycle. Dexamethasone will be given on Days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle for the first 8 cycles. For cycles ≥ 9, dexamethasone will be given on Days 1, 2, 8, 9, 15, 16, 22, 23, 29, and 30 of each 35-day cycle.

    Drug: Bortezomib
    subcutaneous dose of 1.3 mg/m2
    Other Names:
  • Velcade®
  • Drug: Dexamethasone
    oral dose of 20mg

    Outcome Measures

    Primary Outcome Measures

    1. Progression-free Survival (PFS) as Assessed by IRC [From date of randomization until IRC-confirmed documented PD or death, censored date, whichever occurred first (up to 32 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 M-protein levels: the difference between involved and uninvolved free light chain (FLC) levels (absolute increase must be greater than [>] 10 mg/dL); e) in participants without measurable serum and urine M-protein levels and without measurable involved FLC levels: bone marrow plasma cell percentage irrespective of baseline status (absolute increase must be >=10%).

    Secondary Outcome Measures

    1. Overall Response Rate (ORR) as Assessed by IRC [From date of randomization until disease progression or death, whichever occurred first (maximum duration up to 75 months)]

    2. Percentage of Participants With Response Rates [From date of randomization until disease progression or death, whichever occurred first (maximum duration up to 75 months)]

    3. Overall Survival (OS) [From date of randomization to the date of death or censored date, whichever occurred first (maximum duration of 75 months)]

    4. Duration of Response (DOR) as Assessed by IRC [From the first documentation of response to the first documentation of PD or death or censored date, whichever occurred first (maximum duration up to 75 months)]

    5. Time-to-next-treatment (TTNT) [From date of randomization to start of next anti-MM treatment or death, whichever occurs first (maximum duration of 75 months)]

    6. Time-to-response (TTR) as Assessed by IRC [From date of randomization until the date of first IRC confirmed response (maximum duration up to 75 months)]

    7. Number of Participants With Grade >= 2 Peripheral Neuropathy Events [From date of randomization up to 30 days after last dose of treatment (maximum duration of 75 months)]

    8. Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs [From date of randomization up to 30 days after last dose of treatment (maximum duration up to 75 months)]

    9. Patient-reported Peripheral Neuropathy Measured by European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-CIPN20 Instrument [Up to 75 months]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. Histologically confirmed MM with measurable disease per IMWG guidelines as defined by at least 1 of the following:
    • Serum M-protein ≥ 0.5 g/dL (> 5 g/L) by serum protein electrophoresis (SPEP) or for immunoglobulin (Ig) A myeloma, by quantitative serum IgA levels; or

    • Urinary M-protein excretion at least 200 mg/24 hours; or

    • Serum free light chain (FLC) ≥ 100 mg/L, provided that the serum FLC ratio is abnormal.

    1. Had at least 1 prior anti-MM regimen and no more than 3 prior anti-MM regimens. Induction therapy followed by stem cell transplant and consolidation/maintenance therapy will be considered as 1 anti-MM regimen.

    2. Documented evidence of progressive MM (based on the Investigator's determination according to the modified IMWG response criteria) on or after their most recent regimen.

    3. Prior treatment with bortezomib or other Proteasome Inhibitor (PI) is allowed, provided all of the following criteria are met:

    • Best response achieved with prior bortezomib at any time was ≥ PR and with the last PI (PI therapy (alone or in combination) was ≥ PR, AND

    • Participant did not discontinue bortezomib due to ≥ Grade 3 related toxicity, AND

    • Must have had at least a 6-month PI-treatment-free interval prior to Cycle 1 Day 1 (C1D1) of study treatment.

    1. Must have an ECOG Status score of 0, 1, or 2.

    2. Written informed consent in accordance with federal, local, and institutional guidelines.

    3. Age ≥18 years.

    4. Resolution of any clinically significant non-hematological toxicities (if any) from previous treatments to ≤ Grade 1 by C1D1.

    5. Adequate hepatic function within 28 days prior to C1D1.

    6. Adequate renal function within 28 days prior to C1D1.

    7. Adequate hematopoietic function within 7 days prior to C1D1.

    8. Female patients of childbearing potential must have a negative serum pregnancy test at Screening. Female patients of childbearing potential and fertile male patients who are sexually active with a female of childbearing potential must use highly effective methods of contraception throughout the study and for 3 months following the last dose of study treatment.

    Exclusion Criteria:
    1. Prior exposure to a SINE compound (i.e. an XPO-1 inhibitor), including selinexor.

    2. Prior malignancy that required treatment, or has shown evidence of recurrence (except for non-melanoma skin cancer or adequately treated cervical carcinoma in situ) during the 5 years prior to randomization.

    3. Any concurrent medical condition or disease (e.g., uncontrolled active hypertension, uncontrolled active diabetes, active systemic infection, etc.) that is likely to interfere with study procedures.

    4. Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within 1 week prior to C1D1.

    5. Active plasma cell leukemia.

    6. Documented systemic light chain amyloidosis.

    7. MM involving the central nervous system.

    8. Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome.

    9. Spinal cord compression.

    10. Greater than Grade 2 neuropathy or ≥ Grade 2 neuropathy with pain at baseline, regardless of whether or not the patient is currently receiving medication

    11. Known intolerance, hypersensitivity, or contraindication to glucocorticoids.

    12. Radiation, chemotherapy, or immunotherapy or any other anticancer therapy (including investigational therapies) ≤ 2 weeks prior to C1D1. Localized radiation to a single site at least 1 week before C1D1 is permitted. Glucocorticoids within 2 weeks of C1D1 are permitted. Patients on long-term glucocorticoids during Screening do not require a washout period but must be able to tolerate the specified dexamethasone dose in this study.

    13. Prior autologous stem cell transplantation < 1 month or allogeneic stem cell transplantation < 4 months prior to C1D1.

    14. Active graft versus host disease (after allogeneic stem cell transplantation) at C1D1.

    15. Pregnant or breastfeeding females.

    16. Body Surface Area < 1.4 m² at baseline, calculated by the Dubois or Mosteller method.

    17. Life expectancy of < 4 months.

    18. Major surgery within 4 weeks prior to C1D1.

    19. Active, unstable cardiovascular function:

    20. Symptomatic ischemia, or

    21. Uncontrolled clinically significant conduction abnormalities (e.g., patients with ventricular tachycardia on anti-arrhythmics are excluded; patients with first-degree atrioventricular block or asymptomatic left anterior fascicular block/right bundle branch block will not be excluded), or

    22. Congestive heart failure of New York Heart Association Class ≥ 3 or known left ventricular ejection fraction < 40%, or

    23. Myocardial infarction within 3 months prior to C1D1.

    24. Known active human immunodeficiency virus (HIV) infection or HIV seropositivity

    25. Known active hepatitis A, B, or C infection; or known to be positive for hepatitis C virus ribonucleic acid (RNA) or hepatitis B virus surface antigen.

    26. Any active gastrointestinal dysfunction interfering with the patient's ability to swallow tablets, or any active gastrointestinal dysfunction that could interfere with absorption of study treatment.

    27. Any active, serious psychiatric, medical, or other conditions/situations that, in the opinion of the Investigator, could interfere with treatment, compliance, or the ability to give informed consent.

    28. Contraindication to any of the required concomitant drugs or supportive treatments.

    29. Patients unwilling or unable to comply with the protocol, including providing 24-hour urine samples for urine protein electrophoresis at the required time points.

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Boca Raton Clinical Research (BRCR) Medical CenterPlantationFloridaUnited States33324
    2Emory UniversityAtlantaGeorgiaUnited States30322
    3Kaiser Permanente HawaiiHonoluluHawaiiUnited States96817
    4McFarland ClinicAmesIowaUnited States50010
    5Stormont Vail Health Care (Cotton O'Neil Cancer Center )TopekaKansasUnited States66606
    6Commonwealth HematologyDanvilleKentuckyUnited States40422
    7Norton Cancer InstituteLouisvilleKentuckyUnited States40202
    8University of MarylandBaltimoreMarylandUnited States21201
    9Central Care Cancer CenterBolivarMissouriUnited States65613
    10The Valley Hospital Luckow PavilionParamusNew JerseyUnited States07652
    11Mount SinaiNew YorkNew YorkUnited States10029
    12The Cancer Institute at St. Francis HospitalRoslynNew YorkUnited States11576
    13Novant-Forsyth Memorial HospitalWinston-SalemNorth CarolinaUnited States27103
    14University of Cincinnati HealthCincinnatiOhioUnited States45267
    15Southwest Cancer Center of OklahomaLawtonOklahomaUnited States73505
    16Kaiser Permanente Northwest ORPortlandOregonUnited States97210
    17SCOR AnMed Health Cancer CenterAndersonSouth CarolinaUnited States29621
    18Prairie Lakes HealthcareWatertownSouth DakotaUnited States57201
    19Baylor Sammons Cancer CenterDallasTexasUnited States75246
    20University of Texas SouthwesternDallasTexasUnited States75390
    21Calvary Mater NewcastleWaratahNew South WalesAustralia2298
    22Royal Brisbane and Women's HospitalHerstonQueenslandAustralia4029
    23Mater Misericordiae Limited and Mater Medical ResearchSouth BrisbaneQueenslandAustralia4101
    24Gold Coast University HospitalSouthportQueenslandAustralia4215
    25Royal Adelaide HospitalAdelaideSouth AustraliaAustralia5000
    26Flinders Medical CentreBedford ParkSouth AustraliaAustralia5042
    27St. Vincent's Hospital MelbourneFitzroyVictoriaAustralia3065
    28The Alfred HospitalMelbourneVictoriaAustralia3004
    29Medical University Innsbruck, Department of Internal Medicine V (Hematology and Oncology)InnsbruckAustria
    30University Hospital Krems, Department of Internal Medicine IIKremsAustria
    31Medical University of ViennaViennaAustria1090
    32General Hospital HietzingViennaAustria1130
    33Wilhelminen Hospital, Department of Internal Medicine I, Center for Oncology & HematologyViennaAustria1160
    34Jules Bordet InstituteBrusselsBelgium1000
    35UCL Saint-LucBrusselsBelgium
    36University Hospital GhentGhentBelgium9000
    37General Hospital DeltaRoeselareBelgium8800
    38St. Augustinus HospitalWilrijkBelgium2610
    39University Multiprofile Hospital for Active Treatment, Sveti Georgi Clinic of Clinical HematologyPlovdivBulgaria4002
    40University Multiprofile Hospital for Active Treatment, Sveti Ivan Rilski Clinic of HematologySofiaBulgaria1431
    41Specialized Hospital for Active Treatment of Hematological Diseases, Clinic of Hematology, Dept. of Clinical HematologySofiaBulgaria1756
    42Tom Baker Cancer Center/ Alberta Health ServicesCalgaryAlbertaCanadaT2N 4Z6
    43Cross Cancer Institute / University of AlbertaEdmontonAlbertaCanadaT6G 1Z2
    44Vancouver General HospitalVancouverBritish ColumbiaCanadaV5Z 1M9
    45Queen Elizabeth II Health Sciences CenterHalifaxNova ScotiaCanadaB3H 2Y9
    46North East Cancer Centre SudburySudburyOntarioCanadaP3E 5J1
    47Princess Margaret Cancer ResearchTorontoOntarioCanadaM5G 1X5
    48Maisonneuve-Rosemont HospitalMontrealQuebecCanadaH1T 2M4
    49Royal Victoria Hospital / McGill UniversityMontrealQuebecCanadaH3A 1A1
    50L'Hôtel-Dieu de QuébecQuebec CityQuebecCanadaG1R 2J6
    51Saskatchewan Cancer Agency-Allan Blair Cancer CentreReginaSaskatchewanCanadaS4T 7TI
    52Saskatoon Cancer CenterSaskatoonSaskatchewanCanadaS7N 4H4
    53General University Hospital in PraguePraha 2PragueCzechia128 08
    54University Hopsital BrnoBrnoCzechia625 00
    55University Hospital Hradec KraloveHradec KraloveCzechia500 05
    56University Hospital OlomoucOlomoucCzechia775 20
    57University Hospital Ostrava, Dept. of HematooncologyOstravaCzechia708 52
    58University Hospital Kralovske Vinohrady, Clinic of Internal HematologyPragueCzechia100 34
    59Necker Children's Hospital, Department of Adult HematologyParisIle De FranceFrance75015
    60Hospital Center Departmental La Roche-Sur-YonLa Roche-sur-YonFrance85925
    61Claude Huriez HospitalLilleFrance59037
    62South Lyon Hospital CenterLyonFrance69002
    63Brabois Adults Hospital, University Hospital Center of NancyNancyFrance54511
    64Nantes University Hospital CenterNantesFrance44093
    65Saint-Louis HospitalParisFrance75475
    66Miletrie Hospital, University Hospital Center of PoitiersPoitiersFrance86021
    67University Hospital Freiburg, Department of Internal Medicine IFreiburgBaden-WuerttembergGermanyD-79106
    68Klinikum Leverkusen gGmbH Medizinisxhe Klinik 3LeverkusenNorth Rhine WestfaliaGermany51375
    69Group Practice for Hematology and OncologyDresdenSaxonyGermany1307
    70Alexandra General Hospital, Therapeutic ClinicAthensGreece11528
    71General Hospital of Athens "Evangelismos", Department of Hematology and LymphomaAthensGreece
    72University General Hospital of PatraPátraGreece
    73Theageneion Cancer Hospital, Hematology DepartmentThessaloníkiGreece54639
    74Semmelweis University, 1st Department of Internal MedicineBudapestHungaryH-1083
    75Integrated Szent Istvan and Szent laszlo Hospital, Department of Hematology and Stem Cell TransplantationBudapestHungaryH-1097
    76Semmelweis University, 3rd Department of Internal MedicineBudapestHungaryH-1125
    77Kaposi Mor Teaching Hospital, 2nd Department of Internal MedicineKaposvarHungary7400
    78Medical Center of the University of Pecs, Department of HematologyPecsHungary7624
    79Regional Cancer CentrePatnaBiharIndia800014
    80Regional Cancer CentreThiruvananthapuramKeralaIndia695011
    81Prince Aly Khan HospitalMumbaiMaharashtaIndia400010
    82Jaslok Hospital and Research CentreMumbaiMaharashtaIndia400026
    83Bhaktivedanta HospitalThaneMaharashtraIndia401107
    84IMS & SUM HospitalBhubaneswarOdishaIndia751003
    85Postgraduate Institute of Medical Education & Research (PGIMER)ChandigarhPunjabIndia160012
    86Dayanand Medical College & HospitalLudhianaPunjabIndia141001
    87Cancer InstituteChennaiTamil NaduIndia600020
    88SRM Institute of Medical SciencesChennaiTamil NaduIndia600026
    89Saveetha Medical College HospitalChennaiTamil NaduIndia602105
    90G. Kuppuswamy Naidu HospitalCoimbatoreTamil NaduIndia641037
    91Asviratham Speciality HospitalMaduraiTamil NaduIndia625020
    92Meenakshi Mission HospitalMaduraiTamil NaduIndia625107
    93Yashoda HospitalHyderabadTelenganaIndia500082
    94King George's Medical UniversityLucknowUttar PradeshIndia226003
    95Netaji Subhash Chandra Bose Cancer Research InstituteKolkataWest BengalIndia700094
    96Nil Ratan Sircar (NRS) Medical CollegeKolkataWest BengalIndia700120
    97TATA Memorial CentreKolkataWest BengalIndia700160
    98Rajiv Gandhi Cancer HospitalNew DelhiIndia110085
    99Barzilai Medical CenterAshkelonIsrael7830604
    100Rambam Health Care CampusHaifaIsrael3109601
    101Hadassah Medical CenterJerusalemIsrael
    102Rabin Medical CenterPetaẖ TiqwaIsrael49100
    103Hospital Santa Maria of TerniTerniUmbriaItaly05100
    104Azienda Ospedaliero-Universitaria Ospedali RiunitiAnconaItaly60131
    105ASST Papa Giovanni XXIIIBergamoItaly24127
    106Polyclinic S. Orsola-Malpighi, Department of Hematology, Oncology and Laboratory Medicine, Operative Unit of Hematology - CavoBolognaItaly40138
    107University Hospital Careggi, Department of HematologyFlorenceItaly50134
    108University Hospital San Martino, IRCCA, Dept. of Integrative Cancer Therapies, Operative Unit of Clinical HematologyGenoaItaly16132
    109Hospital Niguerda Ca Granda, Department of Hematology and Oncology, Hematology UnitMilanItaly20162
    110Umberto I Polyclinic of Rome, Department of Cellular Biotechnology and Hematology, Hematology CenterRomeItaly00161
    111University Hospital San Giovanni Battista of TurinTurinItaly10126
    112Jan Biziel University Hospital #2 in Bydgoszcz, Department of HematologyBydgoszczPoland85-168
    113Independent Public Healthcare Facility Municipal Hospital Group in Chorzow, Department of HematologyChorzowPoland41-500
    114University Hospital in Krakow, Teaching Unit of the Hematology DepartmentKrakowPoland31-501
    115Independent Public Teaching Hospital No.1 in Lublin, Department of Hematology-Oncology and Bone Marrow TransplantationLublinPoland20-081
    116St. John of Dukla Oncology Center of Lublin, Department of HematologyLublinPoland20-090
    117Military Institute of Medicine, Department of Internal Medicine and HematologyWarsawPoland04-141
    118Nicolaus Copernicus Memorial Provincial Specialist Hospital in Lodz, Department of HematologyŁódźPoland93-513
    119Hyperclnical MedLife PDR Vulturului Brasov, Hematology DepartmentBraşovRomania500366
    120Colentina Clinical Hospital, Department of HematologyBucharestRomania020125
    121Bucharest University Emergency Hospital, Department of HematologyBucharestRomania050098
    122S.P. Botkin City Clinical HospitalMoscowRussian Federation125284
    123N.A. Semashko Central Clinical Hospital #2 under OJSC Russian RailwaysMoscowRussian Federation129128
    124First I.P. Pavlov State Medical University of St. PetersburgSaint PetersburgRussian Federation197022
    125V.A. Almazov North-West Federal Medical Research Center, Chemotherapy of Oncohematology Diseases and Bone Marrow Transplantation Department #1Saint PetersburgRussian Federation197341
    126Clinical Center of Serbia, Clinic of HematologyBelgradeSerbia11000
    127Institute of Oncology and Radiology of Serbia, Clinic of Medical OncologyBelgradeSerbia11000
    128Clinical Center Kragujevac, Clinic of HematologyKragujevacSerbia34 000
    129Clinical Center Nis, Clinic of Hematology and Clinical ImmunologyNisSerbia18 000
    130Clinical Center of Vojvodina, Clinic of HematologyNovi SadSerbia21 000
    131University Hospital of the Canary IslandsLa LagunaSanta Cruz De TenerifeSpain38320
    132Catalan Institute of Oncology (ICO) BadalonaBadalonaSpain08916
    133University Hospital of Vall d'HebronBarcelonaSpain08035
    134University Hospital Infanta Leonor, Department of HematologyMadridSpain28301
    135University Clinical Hospital of Salamanca, Department of HematologySalamancaSpain37007
    136University Hospital Virgen del Rocio (HUVR)SevilleSpain41013
    137Cherkasy Regional Oncology Center, Regional Treatment and Diagnostic Hematology Center, Department of HematologyCherkasyUkraine18009
    138City Clinical Hospital No.4 of Dnipro City Council, City hematology centerDnipropetrovskUkraine
    139BMT Kiev CenterKievUkraine
    140Kiev Cancer InstituteKievUkraine
    141Institute of Blood Pathology and Transfusion Medicine, Department of Hematology with Laboratory GroupLvivUkraine79044
    142Vinnytsia M.I. Pyrohov Regional Clinical Hospital, Department of HematologyVinnytsiaUkraine21018
    143O.F. Herbachevskyi Regional Clinical Hospital, Hematology Department with Intensive Therapy WardsZhytomyrUkraine10008
    144Belfast Heatlh & Social Care Trust Belfast City HospitalBelfastNorthern IrelandUnited KingdomBT9 7AB
    145NHS Tayside Ninewells HospitalDundeeScotlandUnited KingdomDD1 9SY
    146Cardiff & Vale University Health Board University Hospital of WalesCardiffWalesUnited KingdomCF14 4XW
    147University Hospitals Birmingham NHS Foundation Trust Queen Elizabeth HospitalBirminghamUnited KingdomB15 2TH
    148The Leeds Teaching Hospitals NHS Trust St. James University HospitalLeedsUnited KingdomLS9 7TF
    149University Hospitals of Leicester NHS Trust Royal Leicester InfirmaryLeicesterUnited KingdomLE1 5WW
    150Royal Liverpool & Broadgreen University Hospital NHS Trust Royal Liverpool University HospitalLiverpoolUnited KingdomL7 8XP
    151London North West Healthcare NHS Trust Northwick Park HospitalLondonUnited KingdomHA1 3UJ
    152University College LondonLondonUnited KingdomNW3 2PF
    153King's College Hospital NHS Foundation TrustLondonUnited KingdomSE5 9RS
    154Imperial College Healthcare NHS Trust Hammersmith HospitalLondonUnited KingdomW12 0HS
    155The Christie NHS Foundation TrustManchesterUnited KingdomM20 4BX
    156Freeman HospitalNewcastle Upon TyneUnited KingdomNE7 7DN
    157The Royal Wolverhampton NHS Trust New Cross HospitalWolverhamptonUnited KingdomWV10 0QP

    Sponsors and Collaborators

    • Karyopharm Therapeutics Inc

    Investigators

    • Study Director: Michael Kauffman, MD, PhD, Karyopharm Therapeutics Inc

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Karyopharm Therapeutics Inc
    ClinicalTrials.gov Identifier:
    NCT03110562
    Other Study ID Numbers:
    • KCP-330-023
    First Posted:
    Apr 12, 2017
    Last Update Posted:
    Nov 24, 2021
    Last Verified:
    Nov 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Karyopharm Therapeutics Inc
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment DetailsThe study was conducted at 165 sites in 21 countries.
    Pre-assignment DetailA total of 402 participants were enrolled, out of which 399 participants received study treatment. Based on progressive disease (PD) confirmed by the Independent Review Committee (IRC), participants in the Vd arm could crossover to a regimen that included selinexor: 1) SVd treatment (SVdX) for participants who tolerated bortezomib, or 2) SdX for participants who had significant tolerability issues with bortezomib. Data reported were based on primary analysis cut-off date (18-Feb-2020).
    Arm/Group TitleSVd Arm: Selinexor + Bortezomib + DexamethasoneVd Arm: Bortezomib + Dexamethasone
    Arm/Group DescriptionParticipants received a fixed oral dose of 100 milligrams (mg) selinexor tablets (5 tablets of 20 mg each) once weekly (QW) on Days 1, 8, 15, 22, and 29 of each 35-day cycle, along with subcutaneous (SC) injection of 1.3 milligrams per square meter (mg/m^2) bortezomib QW on Days 1, 8, 15, and 22 of each 35-day cycle, and an oral dose of 20 mg of dexamethasone twice weekly (BIW) on Days 1, 2, 8, 9, 15, 16, 22, 23, 29, and 30 of each 35-day cycle until PD confirmed by the IRC, investigator or participant decision to discontinue study treatment, pregnancy, unacceptable AEs or toxicity that could not be managed by supportive care, withdrawal of consent, death, or sponsor decision to terminate the study.Participants received SC injection of 1.3 mg/m^2 bortezomib QW on Days 1, 4, 8, and 11 of each 21-day cycle for the first 8 cycles, followed by greater than or equal to (>=) 9 cycles on Days 1, 8, 15, and 22 of each 35-day cycle, and received oral dose of 20 mg dexamethasone BIW on Days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle for the first 8 cycles and for cycles >= 9 on Days 1, 2, 8, 9, 15, 16, 22, 23, 29, and 30 of each 35-day cycle until PD confirmed by the IRC, investigator or participant decision to discontinue study treatment, pregnancy, unacceptable AEs or toxicity that could not be managed by supportive care, withdrawal of consent, death, or sponsor decision to terminate the study.
    Period Title: Overall Study
    STARTED195207
    Treated195204
    COMPLETED00
    NOT COMPLETED195207

    Baseline Characteristics

    Arm/Group TitleSVd Arm: Selinexor + Bortezomib + DexamethasoneVd Arm: Bortezomib + DexamethasoneTotal
    Arm/Group DescriptionParticipants received a fixed oral dose of 100 mg selinexor tablets (5 tablets of 20 mg each) QW on Days 1, 8, 15, 22, and 29 of each 35-day cycle, along with SC injection of 1.3 mg/m^2 bortezomib QW on Days 1, 8, 15, and 22 of each 35-day cycle, and an oral dose of 20 mg of dexamethasone BIW on Days 1, 2, 8, 9, 15, 16, 22, 23, 29, and 30 of each 35-day cycle until PD confirmed by the IRC, investigator or participant decision to discontinue study treatment, pregnancy, unacceptable AEs or toxicity that could not be managed by supportive care, withdrawal of consent, death, or sponsor decision to terminate the study.Participants received SC injection of 1.3 mg/m^2 bortezomib QW on Days 1, 4, 8, and 11 of each 21-day cycle for the first 8 cycles, followed by >= 9 cycles on Days 1, 8, 15, and 22 of each 35-day cycle, and received oral dose of 20 mg dexamethasone BIW on Days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle for the first 8 cycles and for cycles >= 9 on Days 1, 2, 8, 9, 15, 16, 22, 23, 29, and 30 of each 35-day cycle until PD confirmed by the IRC, investigator or participant decision to discontinue study treatment, pregnancy, unacceptable AEs or toxicity that could not be managed by supportive care, withdrawal of consent, death, or sponsor decision to terminate the study.Total of all reporting groups
    Overall Participants195207402
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    65.3
    (9.56)
    66.7
    (9.35)
    66.0
    (9.47)
    Sex: Female, Male (Count of Participants)
    Female
    80
    41%
    92
    44.4%
    172
    42.8%
    Male
    115
    59%
    115
    55.6%
    230
    57.2%
    Race/Ethnicity, Customized (Count of Participants)
    Asian
    25
    12.8%
    25
    12.1%
    50
    12.4%
    Black or African American
    4
    2.1%
    7
    3.4%
    11
    2.7%
    White
    161
    82.6%
    165
    79.7%
    326
    81.1%
    Other
    0
    0%
    1
    0.5%
    1
    0.2%
    Missing
    5
    2.6%
    9
    4.3%
    14
    3.5%
    Race/Ethnicity, Customized (Count of Participants)
    Hispanic or Latino
    6
    3.1%
    5
    2.4%
    11
    2.7%
    Not Hispanic or Latino
    171
    87.7%
    188
    90.8%
    359
    89.3%
    Not Reported
    14
    7.2%
    11
    5.3%
    25
    6.2%
    Unknown
    4
    2.1%
    2
    1%
    6
    1.5%
    Missing
    0
    0%
    1
    0.5%
    1
    0.2%

    Outcome Measures

    1. Primary Outcome
    TitleProgression-free Survival (PFS) as Assessed by IRC
    DescriptionPFS 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 M-protein levels: the difference between involved and uninvolved free light chain (FLC) levels (absolute increase must be greater than [>] 10 mg/dL); e) in participants without measurable serum and urine M-protein levels and without measurable involved FLC levels: bone marrow plasma cell percentage irrespective of baseline status (absolute increase must be >=10%).
    Time FrameFrom date of randomization until IRC-confirmed documented PD or death, censored date, whichever occurred first (up to 32 months)

    Outcome Measure Data

    Analysis Population Description
    Intent-to-Treat (ITT) population consisted of all participants who were randomized to the study treatment, regardless of whether or not they received the study treatment. Here, "Overall number of participants analyzed" signifies those participants who were evaluable for this outcome measure.
    Arm/Group TitleSVd Arm: Selinexor + Bortezomib + DexamethasoneVd Arm: Bortezomib + Dexamethasone
    Arm/Group DescriptionParticipants received a fixed oral dose of 100 mg selinexor tablets (5 tablets of 20 mg each) QW on Days 1, 8, 15, 22, and 29 of each 35-day cycle, along with SC injection of 1.3 mg/m^2 bortezomib QW on Days 1, 8, 15, and 22 of each 35-day cycle, and an oral dose of 20 mg of dexamethasone BIW on Days 1, 2, 8, 9, 15, 16, 22, 23, 29, and 30 of each 35-day cycle until PD confirmed by the IRC, investigator or participant decision to discontinue study treatment, pregnancy, unacceptable AEs or toxicity that could not be managed by supportive care, withdrawal of consent, death, or sponsor decision to terminate the study.Participants received SC injection of 1.3 mg/m^2 bortezomib QW on Days 1, 4, 8, and 11 of each 21-day cycle for the first 8 cycles, followed by >= 9 cycles on Days 1, 8, 15, and 22 of each 35-day cycle, and received oral dose of 20 mg dexamethasone BIW on Days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle for the first 8 cycles and for cycles >= 9 on Days 1, 2, 8, 9, 15, 16, 22, 23, 29, and 30 of each 35-day cycle until PD confirmed by the IRC, investigator or participant decision to discontinue study treatment, pregnancy, unacceptable AEs or toxicity that could not be managed by supportive care, withdrawal of consent, death, or sponsor decision to terminate the study.
    Measure Participants80124
    Median (95% Confidence Interval) [Months]
    13.93
    9.46
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection SVd Arm: Selinexor + Bortezomib + Dexamethasone, Vd Arm: Bortezomib + Dexamethasone
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesisp-Value0.0075
    Comments
    MethodStratified Log-rank Test
    Comments
    Method of EstimationEstimation ParameterHazard Ratio (HR)
    Estimated Value0.7020
    Confidence Interval (2-Sided) 95%
    0.5279 to 0.9335
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    TitleOverall Response Rate (ORR) as Assessed by IRC
    Description
    Time FrameFrom date of randomization until disease progression or death, whichever occurred first (maximum duration up to 75 months)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    3. Secondary Outcome
    TitlePercentage of Participants With Response Rates
    Description
    Time FrameFrom date of randomization until disease progression or death, whichever occurred first (maximum duration up to 75 months)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    4. Secondary Outcome
    TitleOverall Survival (OS)
    Description
    Time FrameFrom date of randomization to the date of death or censored date, whichever occurred first (maximum duration of 75 months)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    5. Secondary Outcome
    TitleDuration of Response (DOR) as Assessed by IRC
    Description
    Time FrameFrom the first documentation of response to the first documentation of PD or death or censored date, whichever occurred first (maximum duration up to 75 months)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    6. Secondary Outcome
    TitleTime-to-next-treatment (TTNT)
    Description
    Time FrameFrom date of randomization to start of next anti-MM treatment or death, whichever occurs first (maximum duration of 75 months)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    7. Secondary Outcome
    TitleTime-to-response (TTR) as Assessed by IRC
    Description
    Time FrameFrom date of randomization until the date of first IRC confirmed response (maximum duration up to 75 months)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    8. Secondary Outcome
    TitleNumber of Participants With Grade >= 2 Peripheral Neuropathy Events
    Description
    Time FrameFrom date of randomization up to 30 days after last dose of treatment (maximum duration of 75 months)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    9. Secondary Outcome
    TitleNumber of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
    Description
    Time FrameFrom date of randomization up to 30 days after last dose of treatment (maximum duration up to 75 months)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    10. Secondary Outcome
    TitlePatient-reported Peripheral Neuropathy Measured by European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-CIPN20 Instrument
    Description
    Time FrameUp to 75 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description

    Adverse Events

    Time FrameFrom date of randomization up to 30 days after last dose of treatment (up to 32 months )
    Adverse Event Reporting Description
    Arm/Group TitleSVd Arm: Selinexor + Bortezomib + DexamethasoneVd Arm: Bortezomib + Dexamethasone
    Arm/Group DescriptionParticipants received a fixed oral dose of 100 mg selinexor tablets (5 tablets of 20 mg each) QW on Days 1, 8, 15, 22, and 29 of each 35-day cycle, along with SC injection of 1.3 mg/m^2 bortezomib QW on Days 1, 8, 15, and 22 of each 35-day cycle, and an oral dose of 20 mg of dexamethasone BIW on Days 1, 2, 8, 9, 15, 16, 22, 23, 29, and 30 of each 35-day cycle until PD confirmed by the IRC, investigator or participant decision to discontinue study treatment, pregnancy, unacceptable AEs or toxicity that could not be managed by supportive care, withdrawal of consent, death or sponsor decision to terminate the study.Participants received SC injection of 1.3 mg/m^2 bortezomib QW on Days 1, 4, 8, and 11 of each 21-day cycle for the first 8 cycles, followed by >= 9 cycles on Days 1, 8, 15, and 22 of each 35-day cycle, and received oral dose of 20 mg dexamethasone BIW on Days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle for the first 8 cycles and for cycles >= 9 on Days 1, 2, 8, 9, 15, 16, 22, 23, 29, and 30 of each 35-day cycle until PD confirmed by the IRC, investigator or participant decision to discontinue study treatment, pregnancy, unacceptable AEs or toxicity that could not be managed by supportive care, withdrawal of consent, death or sponsor decision to terminate the study.
    All Cause Mortality
    SVd Arm: Selinexor + Bortezomib + DexamethasoneVd Arm: Bortezomib + Dexamethasone
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total47/195 (24.1%) 61/204 (29.9%)
    Serious Adverse Events
    SVd Arm: Selinexor + Bortezomib + DexamethasoneVd Arm: Bortezomib + Dexamethasone
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total101/195 (51.8%) 77/204 (37.7%)
    Blood and lymphatic system disorders
    Anaemia5/195 (2.6%) 3/204 (1.5%)
    Thrombocytopenia3/195 (1.5%) 1/204 (0.5%)
    Febrile neutropenia1/195 (0.5%) 1/204 (0.5%)
    Neutropenia1/195 (0.5%) 0/204 (0%)
    Cardiac disorders
    Atrial fibrillation4/195 (2.1%) 2/204 (1%)
    Cardiac failure congestive1/195 (0.5%) 1/204 (0.5%)
    Myocardial infarction1/195 (0.5%) 1/204 (0.5%)
    Acute myocardial infarction0/195 (0%) 1/204 (0.5%)
    Angina pectoris0/195 (0%) 1/204 (0.5%)
    Atrioventricular block1/195 (0.5%) 0/204 (0%)
    Bradycardia1/195 (0.5%) 0/204 (0%)
    Cardiac arrest1/195 (0.5%) 0/204 (0%)
    Cardiac failure0/195 (0%) 1/204 (0.5%)
    Cardio-respiratory arrest1/195 (0.5%) 0/204 (0%)
    Cardiomyopathy0/195 (0%) 1/204 (0.5%)
    Cardiovascular disorder1/195 (0.5%) 0/204 (0%)
    Left ventricular dysfunction1/195 (0.5%) 0/204 (0%)
    Left ventricular failure0/195 (0%) 1/204 (0.5%)
    Myocardial ischaemia0/195 (0%) 1/204 (0.5%)
    Sinus tachycardia1/195 (0.5%) 0/204 (0%)
    Ventricular arrhythmia1/195 (0.5%) 0/204 (0%)
    Eye disorders
    Cataract4/195 (2.1%) 0/204 (0%)
    Gastrointestinal disorders
    Diarrhoea7/195 (3.6%) 0/204 (0%)
    Vomiting7/195 (3.6%) 0/204 (0%)
    Nausea4/195 (2.1%) 0/204 (0%)
    Constipation1/195 (0.5%) 2/204 (1%)
    Abdominal pain0/195 (0%) 2/204 (1%)
    Colitis1/195 (0.5%) 0/204 (0%)
    Colitis ischaemic1/195 (0.5%) 0/204 (0%)
    Dyspepsia0/195 (0%) 1/204 (0.5%)
    Lower gastrointestinal haemorrhage1/195 (0.5%) 0/204 (0%)
    General disorders
    Asthenia2/195 (1%) 2/204 (1%)
    Pyrexia3/195 (1.5%) 1/204 (0.5%)
    Fatigue2/195 (1%) 1/204 (0.5%)
    General physical health deterioration3/195 (1.5%) 0/204 (0%)
    Chest pain1/195 (0.5%) 1/204 (0.5%)
    Death1/195 (0.5%) 0/204 (0%)
    Multiple organ dysfunction syndrome1/195 (0.5%) 0/204 (0%)
    Non-cardiac chest pain1/195 (0.5%) 0/204 (0%)
    Hepatobiliary disorders
    Cholecystitis acute1/195 (0.5%) 0/204 (0%)
    Cholelithiasis1/195 (0.5%) 0/204 (0%)
    Hepatic cirrhosis0/195 (0%) 1/204 (0.5%)
    Liver disorder1/195 (0.5%) 0/204 (0%)
    Infections and infestations
    Pneumonia23/195 (11.8%) 24/204 (11.8%)
    Lower respiratory tract infection4/195 (2.1%) 3/204 (1.5%)
    Bronchitis3/195 (1.5%) 2/204 (1%)
    Gastroenteritis4/195 (2.1%) 1/204 (0.5%)
    Influenza3/195 (1.5%) 1/204 (0.5%)
    Septic shock4/195 (2.1%) 0/204 (0%)
    Upper respiratory tract infection3/195 (1.5%) 1/204 (0.5%)
    Urinary tract infection4/195 (2.1%) 0/204 (0%)
    Respiratory syncytial virus infection2/195 (1%) 1/204 (0.5%)
    Urosepsis3/195 (1.5%) 0/204 (0%)
    Cellulitis1/195 (0.5%) 1/204 (0.5%)
    Clostridium difficile colitis0/195 (0%) 2/204 (1%)
    Infection1/195 (0.5%) 1/204 (0.5%)
    Pneumonia pneumococcal2/195 (1%) 0/204 (0%)
    Staphylococcal sepsis1/195 (0.5%) 1/204 (0.5%)
    Chest wall abscess0/195 (0%) 1/204 (0.5%)
    Clostridium difficile infection1/195 (0.5%) 0/204 (0%)
    Corona virus infection1/195 (0.5%) 0/204 (0%)
    Escherichia bacteraemia1/195 (0.5%) 0/204 (0%)
    Gangrene0/195 (0%) 1/204 (0.5%)
    Gastroenteritis norovirus1/195 (0.5%) 0/204 (0%)
    H1N1 influenza0/195 (0%) 1/204 (0.5%)
    Laryngitis0/195 (0%) 1/204 (0.5%)
    Meningitis tuberculous1/195 (0.5%) 0/204 (0%)
    Orchitis1/195 (0.5%) 0/204 (0%)
    Pneumonia bacterial1/195 (0.5%) 0/204 (0%)
    Pneumonia fungal1/195 (0.5%) 0/204 (0%)
    Pneumonia influenzal1/195 (0.5%) 0/204 (0%)
    Pneumonia parainfluenzae viral1/195 (0.5%) 0/204 (0%)
    Pneumonia respiratory syncytial viral0/195 (0%) 1/204 (0.5%)
    Pulmonary sepsis0/195 (0%) 1/204 (0.5%)
    Sepsis1/195 (0.5%) 0/204 (0%)
    Injury, poisoning and procedural complications
    Femur fracture2/195 (1%) 1/204 (0.5%)
    Fall2/195 (1%) 0/204 (0%)
    Cervical vertebral fracture0/195 (0%) 1/204 (0.5%)
    Femoral neck fracture0/195 (0%) 1/204 (0.5%)
    Hip fracture1/195 (0.5%) 0/204 (0%)
    Injury1/195 (0.5%) 0/204 (0%)
    Overdose1/195 (0.5%) 0/204 (0%)
    Pelvic fracture1/195 (0.5%) 0/204 (0%)
    Postoperative respiratory failure1/195 (0.5%) 0/204 (0%)
    Rib fracture1/195 (0.5%) 0/204 (0%)
    Subdural haemorrhage0/195 (0%) 1/204 (0.5%)
    Investigations
    Blood glucose abnormal1/195 (0.5%) 0/204 (0%)
    Metabolism and nutrition disorders
    Dehydration3/195 (1.5%) 0/204 (0%)
    Hypokalaemia1/195 (0.5%) 1/204 (0.5%)
    Cachexia1/195 (0.5%) 0/204 (0%)
    Decreased appetite1/195 (0.5%) 0/204 (0%)
    Hyperkalaemia0/195 (0%) 1/204 (0.5%)
    Tumour lysis syndrome0/195 (0%) 1/204 (0.5%)
    Musculoskeletal and connective tissue disorders
    Bone pain1/195 (0.5%) 1/204 (0.5%)
    Back pain0/195 (0%) 1/204 (0.5%)
    Mobility decreased1/195 (0.5%) 0/204 (0%)
    Osteoarthritis1/195 (0.5%) 0/204 (0%)
    Osteochondrosis0/195 (0%) 1/204 (0.5%)
    Spinal pain1/195 (0.5%) 0/204 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Myelodysplastic syndrome0/195 (0%) 1/204 (0.5%)
    Ovarian neoplasm0/195 (0%) 1/204 (0.5%)
    Pancreatic carcinoma metastatic0/195 (0%) 1/204 (0.5%)
    Nervous system disorders
    Cerebral infarction0/195 (0%) 2/204 (1%)
    Neuropathy peripheral0/195 (0%) 2/204 (1%)
    Syncope1/195 (0.5%) 1/204 (0.5%)
    Transient ischaemic attack1/195 (0.5%) 1/204 (0.5%)
    Brain oedema1/195 (0.5%) 0/204 (0%)
    Carotid artery aneurysm1/195 (0.5%) 0/204 (0%)
    Cerebral haemorrhage1/195 (0.5%) 0/204 (0%)
    Cerebral ischaemia1/195 (0.5%) 0/204 (0%)
    Dementia Alzheimer's type1/195 (0.5%) 0/204 (0%)
    Encephalopathy1/195 (0.5%) 0/204 (0%)
    Hepatic encephalopathy0/195 (0%) 1/204 (0.5%)
    Ischaemic stroke0/195 (0%) 1/204 (0.5%)
    Metabolic encephalopathy1/195 (0.5%) 0/204 (0%)
    Neuralgia0/195 (0%) 1/204 (0.5%)
    Paraesthesia0/195 (0%) 1/204 (0.5%)
    Presyncope0/195 (0%) 1/204 (0.5%)
    Vascular dementia1/195 (0.5%) 0/204 (0%)
    Psychiatric disorders
    Affect lability1/195 (0.5%) 0/204 (0%)
    Mixed anxiety and depressive disorder1/195 (0.5%) 0/204 (0%)
    Personality change1/195 (0.5%) 0/204 (0%)
    Reactive psychosis1/195 (0.5%) 0/204 (0%)
    Renal and urinary disorders
    Acute kidney injury4/195 (2.1%) 2/204 (1%)
    Haematuria1/195 (0.5%) 0/204 (0%)
    Reproductive system and breast disorders
    Pelvic prolapse1/195 (0.5%) 0/204 (0%)
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease1/195 (0.5%) 2/204 (1%)
    Dyspnoea2/195 (1%) 1/204 (0.5%)
    Epistaxis3/195 (1.5%) 0/204 (0%)
    Pulmonary embolism2/195 (1%) 1/204 (0.5%)
    Pulmonary oedema1/195 (0.5%) 1/204 (0.5%)
    Acute respiratory failure1/195 (0.5%) 0/204 (0%)
    Bronchiectasis1/195 (0.5%) 0/204 (0%)
    Bronchospasm1/195 (0.5%) 0/204 (0%)
    Pneumonitis1/195 (0.5%) 0/204 (0%)
    Vascular disorders
    Deep vein thrombosis1/195 (0.5%) 2/204 (1%)
    Blood pressure fluctuation1/195 (0.5%) 0/204 (0%)
    Circulatory collapse0/195 (0%) 1/204 (0.5%)
    Embolism0/195 (0%) 1/204 (0.5%)
    Hypotension1/195 (0.5%) 0/204 (0%)
    Orthostatic hypotension0/195 (0%) 1/204 (0.5%)
    Peripheral ischaemia0/195 (0%) 1/204 (0.5%)
    Shock haemorrhagic1/195 (0.5%) 0/204 (0%)
    Other (Not Including Serious) Adverse Events
    SVd Arm: Selinexor + Bortezomib + DexamethasoneVd Arm: Bortezomib + Dexamethasone
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total193/195 (99%) 197/204 (96.6%)
    Blood and lymphatic system disorders
    Thrombocytopenia116/195 (59.5%) 55/204 (27%)
    Anaemia71/195 (36.4%) 45/204 (22.1%)
    Neutropenia29/195 (14.9%) 12/204 (5.9%)
    Leukopenia10/195 (5.1%) 3/204 (1.5%)
    Lymphopenia11/195 (5.6%) 4/204 (2%)
    Cardiac disorders
    Tachycardia10/195 (5.1%) 3/204 (1.5%)
    Eye disorders
    Cataract39/195 (20%) 13/204 (6.4%)
    Vision blurred13/195 (6.7%) 8/204 (3.9%)
    Visual impairment11/195 (5.6%) 4/204 (2%)
    Gastrointestinal disorders
    Nausea98/195 (50.3%) 20/204 (9.8%)
    Diarrhoea60/195 (30.8%) 51/204 (25%)
    Constipation33/195 (16.9%) 34/204 (16.7%)
    Vomiting39/195 (20%) 9/204 (4.4%)
    Abdominal pain15/195 (7.7%) 11/204 (5.4%)
    General disorders
    Fatigue82/195 (42.1%) 37/204 (18.1%)
    Asthenia47/195 (24.1%) 25/204 (12.3%)
    Oedema peripheral23/195 (11.8%) 26/204 (12.7%)
    Pyrexia28/195 (14.4%) 21/204 (10.3%)
    Infections and infestations
    Upper respiratory tract infection32/195 (16.4%) 29/204 (14.2%)
    Bronchitis21/195 (10.8%) 18/204 (8.8%)
    Nasopharyngitis23/195 (11.8%) 10/204 (4.9%)
    Pneumonia12/195 (6.2%) 9/204 (4.4%)
    Urinary tract infection12/195 (6.2%) 9/204 (4.4%)
    Lower respiratory tract infection12/195 (6.2%) 8/204 (3.9%)
    Investigations
    Weight decreased51/195 (26.2%) 25/204 (12.3%)
    Alanine aminotransferase increased13/195 (6.7%) 7/204 (3.4%)
    Metabolism and nutrition disorders
    Decreased appetite69/195 (35.4%) 11/204 (5.4%)
    Hypokalaemia18/195 (9.2%) 9/204 (4.4%)
    Hyperglycaemia14/195 (7.2%) 11/204 (5.4%)
    Hypophosphataemia16/195 (8.2%) 6/204 (2.9%)
    Hypercreatininaemia13/195 (6.7%) 7/204 (3.4%)
    Hypocalcaemia15/195 (7.7%) 5/204 (2.5%)
    Hyponatraemia15/195 (7.7%) 3/204 (1.5%)
    Musculoskeletal and connective tissue disorders
    Back pain30/195 (15.4%) 28/204 (13.7%)
    Pain in extremity9/195 (4.6%) 17/204 (8.3%)
    Arthralgia8/195 (4.1%) 12/204 (5.9%)
    Muscle spasms3/195 (1.5%) 12/204 (5.9%)
    Nervous system disorders
    Neuropathy peripheral63/195 (32.3%) 96/204 (47.1%)
    Dizziness24/195 (12.3%) 8/204 (3.9%)
    Headache19/195 (9.7%) 11/204 (5.4%)
    Paraesthesia5/195 (2.6%) 15/204 (7.4%)
    Dysgeusia13/195 (6.7%) 1/204 (0.5%)
    Psychiatric disorders
    Insomnia31/195 (15.9%) 32/204 (15.7%)
    Confusional state16/195 (8.2%) 2/204 (1%)
    Respiratory, thoracic and mediastinal disorders
    Cough35/195 (17.9%) 30/204 (14.7%)
    Dyspnoea18/195 (9.2%) 26/204 (12.7%)
    Dyspnoea exertional10/195 (5.1%) 8/204 (3.9%)
    Oropharyngeal pain12/195 (6.2%) 4/204 (2%)
    Epistaxis10/195 (5.1%) 3/204 (1.5%)
    Vascular disorders
    Hypertension17/195 (8.7%) 16/204 (7.8%)
    Hypotension10/195 (5.1%) 11/204 (5.4%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Results Point of Contact

    Name/TitleJatin Shah, MD
    OrganizationKaryopharm Therapeutics Inc.
    Phone(617) 658-0600
    Emailjshah@karyopharm.com
    Responsible Party:
    Karyopharm Therapeutics Inc
    ClinicalTrials.gov Identifier:
    NCT03110562
    Other Study ID Numbers:
    • KCP-330-023
    First Posted:
    Apr 12, 2017
    Last Update Posted:
    Nov 24, 2021
    Last Verified:
    Nov 1, 2021