Bortezomib, Selinexor, and Dexamethasone in Patients With Multiple Myeloma (BOSTON)

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)

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.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Selinexor; Drug: Bortezomib; Drug: Dexamethasone

• Study Type: Interventional
• Enrollment (Actual): 402
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Waratah, New South Wales, Australia, 2298
      • Calvary Mater Newcastle
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Royal Brisbane and Women's Hospital
    • South Brisbane, Queensland, Australia, 4101
      • Mater Misericordiae Limited and Mater Medical Research
    • Southport, Queensland, Australia, 4215
      • Gold Coast University Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
    • Bedford Park, South Australia, Australia, 5042
      • Flinders Medical Centre
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
      • St. Vincent's Hospital Melbourne
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital
• Austria
  • Innsbruck, Austria
    • Medical University Innsbruck, Department of Internal Medicine V (Hematology and Oncology)
  • Krems, Austria
    • University Hospital Krems, Department of Internal Medicine II
  • Vienna, Austria, 1090
    • Medical University of Vienna
  • Vienna, Austria, 1130
    • General Hospital Hietzing
  • Vienna, Austria, 1160
    • Wilhelminen Hospital, Department of Internal Medicine I, Center for Oncology & Hematology
• Belgium
  • Brussels, Belgium, 1000
    • Jules Bordet Institute
  • Brussels, Belgium
    • UCL Saint-Luc
  • Ghent, Belgium, 9000
    • University Hospital Ghent
  • Roeselare, Belgium, 8800
    • General Hospital Delta
  • Wilrijk, Belgium, 2610
    • St. Augustinus Hospital
• Bulgaria
  • Plovdiv, Bulgaria, 4002
    • University Multiprofile Hospital for Active Treatment, Sveti Georgi Clinic of Clinical Hematology
  • Sofia, Bulgaria, 1431
    • University Multiprofile Hospital for Active Treatment, Sveti Ivan Rilski Clinic of Hematology
  • Sofia, Bulgaria, 1756
    • Specialized Hospital for Active Treatment of Hematological Diseases, Clinic of Hematology, Dept. of Clinical Hematology
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
      • Tom Baker Cancer Center/ Alberta Health Services
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute / University of Alberta
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Vancouver General Hospital
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • Queen Elizabeth II Health Sciences Center
  • Ontario
    • Sudbury, Ontario, Canada, P3E 5J1
      • North East Cancer Centre Sudbury
    • Toronto, Ontario, Canada, M5G 1X5
      • Princess Margaret Cancer Research
  • Quebec
    • Montreal, Quebec, Canada, H1T 2M4
      • Maisonneuve-Rosemont Hospital
    • Montreal, Quebec, Canada, H3A 1A1
      • Royal Victoria Hospital / McGill University
    • Quebec City, Quebec, Canada, G1R 2J6
      • L'Hôtel-Dieu de Québec
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4T 7TI
      • Saskatchewan Cancer Agency-Allan Blair Cancer Centre
    • Saskatoon, Saskatchewan, Canada, S7N 4H4
      • Saskatoon Cancer Center
• Czechia
  • Brno, Czechia, 625 00
    • University Hopsital Brno
  • Hradec Kralove, Czechia, 500 05
    • University hospital Hradec Králové
  • Olomouc, Czechia, 775 20
    • University Hospital Olomouc
  • Ostrava, Czechia, 708 52
    • University Hospital Ostrava, Dept. of Hematooncology
  • Prague, Czechia, 100 34
    • University Hospital Kralovske Vinohrady, Clinic of Internal Hematology
  • Prague
    • Praha 2, Prague, Czechia, 128 08
      • General University Hospital in Prague
• France
  • La Roche-sur-Yon, France, 85925
    • Hospital Center Departmental La Roche-Sur-Yon
  • Lille, France, 59037
    • Claude Huriez hospital
  • Lyon, France, 69002
    • South Lyon Hospital Center
  • Nancy, France, 54511
    • Brabois Adults Hospital, University Hospital Center of Nancy
  • Nantes, France, 44093
    • Nantes University Hospital Center
  • Paris, France, 75475
    • Saint-Louis Hospital
  • Poitiers, France, 86021
    • Miletrie Hospital, University Hospital Center of Poitiers
  • Ile De France
    • Paris, Ile De France, France, 75015
      • Necker Children's Hospital, Department of Adult Hematology
• Germany
  • Baden-Wuerttemberg
    • Freiburg, Baden-Wuerttemberg, Germany, D-79106
      • University Hospital Freiburg, Department of Internal Medicine I
  • North Rhine Westfalia
    • Leverkusen, North Rhine Westfalia, Germany, 51375
      • Klinikum Leverkusen gGmbH Medizinisxhe Klinik 3
  • Saxony
    • Dresden, Saxony, Germany, 1307
      • Group Practice for Hematology and Oncology
• Greece
  • Athens, Greece, 11528
    • Alexandra General Hospital, Therapeutic Clinic
  • Athens, Greece
    • General Hospital of Athens "Evangelismos", Department of Hematology and Lymphoma
  • Pátra, Greece
    • University General Hospital of Patra
  • Thessaloníki, Greece, 54639
    • Theageneion Cancer Hospital, Hematology Department
• Hungary
  • Budapest, Hungary, H-1083
    • Semmelweis University, 1st Department of Internal Medicine
  • Budapest, Hungary, H-1097
    • Integrated Szent Istvan and Szent laszlo Hospital, Department of Hematology and Stem Cell Transplantation
  • Budapest, Hungary, H-1125
    • Semmelweis University, 3rd Department of Internal Medicine
  • Kaposvar, Hungary, 7400
    • Kaposi Mor Teaching Hospital, 2nd Department of Internal Medicine
  • Pecs, Hungary, 7624
    • Medical Center of the University of Pecs, Department of Hematology
• India
  • New Delhi, India, 110085
    • Rajiv Gandhi Cancer Hospital
  • Bihar
    • Patna, Bihar, India, 800014
      • Regional Cancer Centre
  • Kerala
    • Thiruvananthapuram, Kerala, India, 695011
      • Regional Cancer Centre
  • Maharashta
    • Mumbai, Maharashta, India, 400010
      • Prince Aly Khan Hospital
    • Mumbai, Maharashta, India, 400026
      • Jaslok Hospital and Research Centre
  • Maharashtra
    • Thane, Maharashtra, India, 401107
      • Bhaktivedanta Hospital
  • Odisha
    • Bhubaneswar, Odisha, India, 751003
      • IMS & SUM Hospital
  • Punjab
    • Chandigarh, Punjab, India, 160012
      • Postgraduate Institute of Medical Education & Research (PGIMER)
    • Ludhiana, Punjab, India, 141001
      • Dayanand Medical College & Hospital
  • Tamil Nadu
    • Chennai, Tamil Nadu, India, 600020
      • Cancer Institute
    • Chennai, Tamil Nadu, India, 600026
      • SRM Institute of Medical Sciences
    • Chennai, Tamil Nadu, India, 602105
      • Saveetha Medical College Hospital
    • Coimbatore, Tamil Nadu, India, 641037
      • G. Kuppuswamy Naidu Hospital
    • Madurai, Tamil Nadu, India, 625020
      • Asviratham Speciality Hospital
    • Madurai, Tamil Nadu, India, 625107
      • Meenakshi Mission Hospital
  • Telengana
    • Hyderabad, Telengana, India, 500082
      • Yashoda Hospital
  • Uttar Pradesh
    • Lucknow, Uttar Pradesh, India, 226003
      • King George's Medical University
  • West Bengal
    • Kolkata, West Bengal, India, 700094
      • Netaji Subhash Chandra Bose Cancer Research Institute
    • Kolkata, West Bengal, India, 700120
      • Nil Ratan Sircar (NRS) Medical College
    • Kolkata, West Bengal, India, 700160
      • Tata Memorial Centre
• Israel
  • Ashkelon, Israel, 7830604
    • Barzilai Medical Center
  • Haifa, Israel, 3109601
    • Rambam Health Care Campus
  • Jerusalem, Israel
    • Hadassah Medical Center
  • Petaẖ Tiqwa, Israel, 49100
    • Rabin Medical Center
• Italy
  • Ancona, Italy, 60131
    • Azienda Ospedaliero-Universitaria Ospedali Riuniti
  • Bergamo, Italy, 24127
    • Asst Papa Giovanni Xxiii
  • Bologna, Italy, 40138
    • Polyclinic S. Orsola-Malpighi, Department of Hematology, Oncology and Laboratory Medicine, Operative Unit of Hematology - Cavo
  • Florence, Italy, 50134
    • University Hospital Careggi, Department of Hematology
  • Genoa, Italy, 16132
    • University Hospital San Martino, IRCCA, Dept. of Integrative Cancer Therapies, Operative Unit of Clinical Hematology
  • Milan, Italy, 20162
    • Hospital Niguerda Ca Granda, Department of Hematology and Oncology, Hematology Unit
  • Rome, Italy, 00161
    • Umberto I Polyclinic of Rome, Department of Cellular Biotechnology and Hematology, Hematology Center
  • Turin, Italy, 10126
    • University Hospital San Giovanni Battista of Turin
  • Umbria
    • Terni, Umbria, Italy, 05100
      • Hospital Santa Maria of Terni
• Poland
  • Bydgoszcz, Poland, 85-168
    • Jan Biziel University Hospital #2 in Bydgoszcz, Department of Hematology
  • Chorzow, Poland, 41-500
    • Independent Public Healthcare Facility Municipal Hospital Group in Chorzow, Department of Hematology
  • Krakow, Poland, 31-501
    • University Hospital in Krakow, Teaching Unit of the Hematology Department
  • Lublin, Poland, 20-081
    • Independent Public Teaching Hospital No.1 in Lublin, Department of Hematology-Oncology and Bone Marrow Transplantation
  • Lublin, Poland, 20-090
    • St. John of Dukla Oncology Center of Lublin, Department of Hematology
  • Warsaw, Poland, 04-141
    • Military Institute of Medicine, Department of Internal Medicine and Hematology
  • Łódź, Poland, 93-513
    • Nicolaus Copernicus Memorial Provincial Specialist Hospital in Lodz, Department of Hematology
• Romania
  • Braşov, Romania, 500366
    • Hyperclnical MedLife PDR Vulturului Brasov, Hematology Department
  • Bucharest, Romania, 020125
    • Colentina Clinical Hospital, Department of Hematology
  • Bucharest, Romania, 050098
    • Bucharest University Emergency Hospital, Department of Hematology
• Russian Federation
  • Moscow, Russian Federation, 125284
    • S.P. Botkin City Clinical Hospital
  • Moscow, Russian Federation, 129128
    • N.A. Semashko Central Clinical Hospital #2 under OJSC Russian Railways
  • Saint Petersburg, Russian Federation, 197022
    • First I.P. Pavlov State Medical University of St. Petersburg
  • Saint Petersburg, Russian Federation, 197341
    • V.A. Almazov North-West Federal Medical Research Center, Chemotherapy of Oncohematology Diseases and Bone Marrow Transplantation Department #1
• Serbia
  • Belgrade, Serbia, 11000
    • Clinical Center of Serbia, Clinic of Hematology
  • Belgrade, Serbia, 11000
    • Institute of Oncology and Radiology of Serbia, Clinic of Medical Oncology
  • Kragujevac, Serbia, 34 000
    • Clinical Center Kragujevac, Clinic of Hematology
  • Nis, Serbia, 18 000
    • Clinical Center Nis, Clinic of Hematology and Clinical Immunology
  • Novi Sad, Serbia, 21 000
    • Clinical Center of Vojvodina, Clinic of Hematology
• Spain
  • Badalona, Spain, 08916
    • Catalan Institute of Oncology (ICO) Badalona
  • Barcelona, Spain, 08035
    • University Hospital of Vall d'Hebron
  • Madrid, Spain, 28301
    • University Hospital Infanta Leonor, Department of Hematology
  • Salamanca, Spain, 37007
    • University Clinical Hospital of Salamanca, Department of Hematology
  • Seville, Spain, 41013
    • University Hospital Virgen del Rocio (HUVR)
  • Santa Cruz De Tenerife
    • La Laguna, Santa Cruz De Tenerife, Spain, 38320
      • University Hospital of the Canary Islands
• Ukraine
  • Cherkasy, Ukraine, 18009
    • Cherkasy Regional Oncology Center, Regional Treatment and Diagnostic Hematology Center, Department of Hematology
  • Dnipropetrovsk, Ukraine
    • City Clinical Hospital No.4 of Dnipro City Council, City hematology center
  • Kiev, Ukraine
    • BMT Kiev Center
  • Kiev, Ukraine
    • Kiev Cancer Institute
  • Lviv, Ukraine, 79044
    • Institute of Blood Pathology and Transfusion Medicine, Department of Hematology with Laboratory Group
  • Vinnytsia, Ukraine, 21018
    • Vinnytsia M.I. Pyrohov Regional Clinical Hospital, Department of Hematology
  • Zhytomyr, Ukraine, 10008
    • O.F. Herbachevskyi Regional Clinical Hospital, Hematology Department with Intensive Therapy Wards
• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
    • University Hospitals Birmingham NHS Foundation Trust Queen Elizabeth Hospital
  • Leeds, United Kingdom, LS9 7TF
    • The Leeds Teaching Hospitals NHS Trust St. James University Hospital
  • Leicester, United Kingdom, LE1 5WW
    • University Hospitals of Leicester NHS Trust Royal Leicester Infirmary
  • Liverpool, United Kingdom, L7 8XP
    • Royal Liverpool & Broadgreen University Hospital NHS Trust Royal Liverpool University Hospital
  • London, United Kingdom, SE5 9RS
    • King's College Hospital NHS Foundation Trust
  • London, United Kingdom, NW3 2PF
    • University College London
  • London, United Kingdom, HA1 3UJ
    • London North West Healthcare NHS Trust Northwick Park Hospital
  • London, United Kingdom, W12 0HS
    • Imperial College Healthcare NHS Trust Hammersmith Hospital
  • Manchester, United Kingdom, M20 4BX
    • The Christie NHS Foundation Trust
  • Newcastle Upon Tyne, United Kingdom, NE7 7DN
    • Freeman Hospital
  • Wolverhampton, United Kingdom, WV10 0QP
    • The Royal Wolverhampton NHS Trust New Cross Hospital
  • Northern Ireland
    • Belfast, Northern Ireland, United Kingdom, BT9 7AB
      • Belfast Heatlh & Social Care Trust Belfast City Hospital
  • Scotland
    • Dundee, Scotland, United Kingdom, DD1 9SY
      • NHS Tayside Ninewells Hospital
  • Wales
    • Cardiff, Wales, United Kingdom, CF14 4XW
      • Cardiff & Vale University Health Board University Hospital of Wales
• United States
  • Florida
    • Plantation, Florida, United States, 33324
      • Boca Raton Clinical Research (BRCR) Medical Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Hawaii
    • Honolulu, Hawaii, United States, 96817
      • Kaiser Permanente Hawaii
  • Iowa
    • Ames, Iowa, United States, 50010
      • McFarland Clinic
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Stormont Vail Health Care (Cotton O'Neil Cancer Center )
  • Kentucky
    • Danville, Kentucky, United States, 40422
      • Commonwealth Hematology
    • Louisville, Kentucky, United States, 40202
      • Norton Cancer Institute
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland
  • Missouri
    • Bolivar, Missouri, United States, 65613
      • Central Care Cancer Center
  • New Jersey
    • Paramus, New Jersey, United States, 07652
      • The Valley Hospital Luckow Pavilion
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai
    • Roslyn, New York, United States, 11576
      • The Cancer Institute at St. Francis Hospital
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27103
      • Novant-Forsyth Memorial Hospital
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati Health
  • Oklahoma
    • Lawton, Oklahoma, United States, 73505
      • Southwest Cancer Center of Oklahoma
  • Oregon
    • Portland, Oregon, United States, 97210
      • Kaiser Permanente Northwest OR
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • SCOR AnMed Health Cancer Center
  • South Dakota
    • Watertown, South Dakota, United States, 57201
      • Prairie Lakes Healthcare
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern
    • Dallas, Texas, United States, 75246
      • Baylor Sammons Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histologically confirmed MM with measurable disease per IMWG guidelines as defined by at least 1 of the following:

   1. 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
   2. Urinary M-protein excretion at least 200 mg/24 hours; or
   3. Serum free light chain (FLC) ≥ 100 mg/L, provided that the serum FLC ratio is abnormal (normal FLC ratio: 0.26 to 1.65).
2. 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.
3. 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.

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

   1. 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
   2. Participant did not discontinue bortezomib due to ≥ Grade 3 related toxicity, AND
   3. Must have had at least a 6-month PI-treatment-free interval prior to Cycle 1 Day 1 (C1D1) of study treatment.
5. Must have an ECOG Status score of 0, 1, or 2.
6. Written informed consent in accordance with federal, local, and institutional guidelines.
7. Age ≥18 years.
8. Resolution of any clinically significant non-hematological toxicities (if any) from previous treatments to ≤ Grade 1 by C1D1. Patients with chronic, stable Grade 2 non-hematological toxicities may be included following approval from the Medical Monitor.

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

   1. Total bilirubin <1.5 × upper limit of normal (ULN) (except patients with Gilbert's syndrome who must have a total bilirubin of <3 × ULN), and
   2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) normal to <2 × ULN.
10. Adequate renal function within 28 days prior to C1D1 (estimated creatinine clearance [CrCl] of ≥20 mL/min, calculated using the formula of Cockroft and Gault):

(140-Age) × Mass (kg)/(72 × creatinine mg/dL) Multiply by 0.85 if the patient is female, or if CrCl is ≥20 mL/min as measured by 24-hour urine collection.

11. Adequate hematopoietic function within 7 days prior to C1D1: total white blood cell (WBC) count ≥1500/mm3, absolute neutrophil count ≥1000/mm3, hemoglobin ≥8.5 g/dL and platelet count ≥75,000/mm3 (patients for whom < 50% of bone marrow nucleated cells are plasma cells) or ≥50,000/mm3 (patients for whom ≥50% of bone marrow nucleated cells are plasma cells).

1. Patients receiving hematopoietic growth factor support, including erythropoietin, darbepoetin, granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), and platelet stimulators (eg, eltrombopag, romiplostim, or interleukin-11) must have a 2-week interval between growth factor support and the Screening assessments, but they may receive growth factor support during the study.

2. Patients must have:

   • At least a 2-week interval from the last red blood cell (RBC) transfusion prior to the Screening hemoglobin assessment, and
   • At least a 1-week interval from the last platelet transfusion prior to the Screening platelet assessment.

However, patients may receive RBC and/or platelet transfusions as clinically indicated per institutional guidelines during the study.

12. 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. Cancer treated with curative intent for >5 years previously and without evidence of recurrence will be allowed.
3. Has 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. Patients on prophylactic antibiotics or with a controlled infection within 1 week prior to C1D1 are acceptable.
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:

    1. Symptomatic ischemia, or
    2. 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
    3. Congestive heart failure of New York Heart Association Class ≥ 3 or known left ventricular ejection fraction < 40%, or
    4. Myocardial infarction within 3 months prior to C1D1.
20. Known active human immunodeficiency virus (HIV) infection or HIV seropositivity
21. 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.
22. 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.
23. 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.
24. Contraindication to any of the required concomitant drugs or supportive treatments.
25. Patients unwilling or unable to comply with the protocol, including providing 24-hour urine samples for urine protein electrophoresis at the required time points.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SVd Arm: Selinexor + Bortezomib + Dexamethasone; Participants 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.	Drug: Selinexor; oral 100 mg dose; Drug: Bortezomib; subcutaneous dose of 1.3 mg/m2; Other Names: Velcade®; Drug: Dexamethasone; oral dose of 20mg
Experimental: Vd Arm: Bortezomib + Dexamethasone; Participants received SC injection of 1.3 mg/m^2 bortezomib 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.	Drug: Bortezomib; subcutaneous dose of 1.3 mg/m2; Other Names: Velcade®; Drug: Dexamethasone; oral dose of 20mg
Experimental: SVdX Arm: Selinexor + Bortezomib + Dexamethasone; Participants in the VD arm who had IRC-confirmed PD and were able to tolerate continued bortezomib treatment had crossed over to receive 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.	Drug: Selinexor; oral 100 mg dose; Drug: Bortezomib; subcutaneous dose of 1.3 mg/m2; Other Names: Velcade®; Drug: Dexamethasone; oral dose of 20mg
Experimental: SdX Arm: Selinexor + Dexamethasone; Participants in the VD arm who had IRC-confirmed PD and were unable to tolerate continued bortezomib treatment had crossed over to receive 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 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.	Drug: Selinexor; oral 100 mg dose; Drug: Dexamethasone; oral dose of 20mg

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SVd/Vd Arm: Overall Response Rate (ORR) as Assessed by IRC	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 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 any soft tissue plasmacytomas and <= 5% plasma cells in bone marrow; or stringent complete response (sCR): CR as defined as Normal free light chain (FLC) ratio + Absence of clonal cells by immunohistochemistry.	From date of randomization until disease progression or initiating a new MM treatment (up to 33 months)
SVd/Vd Arm: Percentage of Participants With Response Rate of Very Good Partial Response (VGPR) or Better Based on IRC Assessment	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.	From date of randomization until confirmed PD or initiating a new MM treatment (up to 33 months)
SVd/Vd Arm: Number of Participants With at Least One Grade Greater Than or Equal to [>=] 2 Peripheral Neuropathy Events	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 intervention. Number of participants experiencing at least one Grade >= 2 peripheral neuropathy event have been reported.	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)
SVd/Vd Arm: Overall Survival (OS)	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.	From date of randomization to the date of death or censored date, whichever occurred first (up to 45 months)
SVd/Vd Arm: Duration of Response (DOR) as Assessed by IRC	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 must be >= 200 mg per 24 hours). Analysis was performed using Kaplan-Meier method.	From the first documentation of response to the first documentation of PD or death, whichever occurred first (up to 45 months)
SVdX Arm: Overall Response Rate (ORR1) as Assessed by IRC During SVdX Treatment	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 any soft tissue plasmacytomas and <=5% plasma cells in bone marrow; or sCR: CR as defined as Normal FLC ratio+ Absence of clonal cells in bone marrow biopsy by immunohistochemistry.	From date of first SVdX treatment until disease progression or initiating a new MM treatment (up to 33 months)
SVdX Arm: Progression Free Survival1 (PFS1) as Assessed by IRC During SVdX Treatment	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-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%).	From date of first SVdX treatment until IRC-confirmed documented PD or death or censored date, whichever occurred first (up to 33 months)
SVd/Vd Arm: Time-to-next-treatment (TTNT) in Participants Randomized to the SVd and Vd Arm Who Received Treatment After SVd/Vd	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.	From date of randomization to start of next anti-MM treatment or death, whichever occurred first (up to 33 months)
SVd/Vd Arm: Time To Response (TTR) in Participants Randomized to the SVd and Vd Arm	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 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 any soft tissue plasmacytomas and <= 5% plasma cells in bone marrow; or sCR: Normal free light chain (FLC) ratio + Absence of clonal cells by immunohistochemistry.	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)
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	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 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%).	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)
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	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 autonomic raw scale scores range from 1 to 12 for men and 1-8 for women (erectile function item is excluded). All scale scores are linearly converted to a total score with range of 0-100 scale, with higher scores indicating more symptom burden.	Svd Arm: Baseline up to End of treatment (EOT) (at Day 820); Vd Arm: Baseline up to EOT (at Day 848)

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Delimpasi S, Mateos MV, Auner HW, Gavriatopoulou M, Dimopoulos MA, Quach H, Pylypenko H, Hajek R, Leleu X, Dolai TK, Sinha DK, Venner CP, Benjamin R, Garg MK, Doronin V, Levy Y, Moreau P, Chai Y, Arazy M, Shah J, Shacham S, Kauffman MG, Richardson PG, Grosicki S. Efficacy and tolerability of once-weekly selinexor, bortezomib, and dexamethasone in comparison with standard twice-weekly bortezomib and dexamethasone in previously treated multiple myeloma with renal impairment: Subgroup analysis from the BOSTON study. Am J Hematol. 2022 Mar 1;97(3):E83-E86. doi: 10.1002/ajh.26434. Epub 2021 Dec 29. No abstract available.
• Richard S, Chari A, Delimpasi S, Simonova M, Spicka I, Pour L, Kriachok I, Dimopoulos MA, Pylypenko H, Auner HW, Leleu X, Usenko G, Hajek R, Benjamin R, Dolai TK, Sinha DK, Venner CP, Garg M, Stevens DA, Quach H, Jagannath S, Moreau P, Levy M, Badros A, Anderson LD Jr, Bahlis NJ, Facon T, Mateos MV, Cavo M, Chang H, Landesman Y, Chai Y, Arazy M, Shah J, Shacham S, Kauffman MG, Grosicki S, Richardson PG. Selinexor, bortezomib, and dexamethasone versus bortezomib and dexamethasone in previously treated multiple myeloma: Outcomes by cytogenetic risk. Am J Hematol. 2021 Sep 1;96(9):1120-1130. doi: 10.1002/ajh.26261. Epub 2021 Jul 5.
• Mateos MV, Gavriatopoulou M, Facon T, Auner HW, Leleu X, Hajek R, Dimopoulos MA, Delimpasi S, Simonova M, Spicka I, Pour L, Kriachok I, Pylypenko H, Doronin V, Usenko G, Benjamin R, Dolai TK, Sinha DK, Venner CP, Garg M, Stevens DA, Quach H, Jagannath S, Moreau P, Levy M, Badros AZ, Anderson LD Jr, Bahlis NJ, Cavo M, Chai Y, Jeha J, Arazy M, Shah J, Shacham S, Kauffman MG, Richardson PG, Grosicki S. Effect of prior treatments on selinexor, bortezomib, and dexamethasone in previously treated multiple myeloma. J Hematol Oncol. 2021 Apr 13;14(1):59. doi: 10.1186/s13045-021-01071-9.
• Auner HW, Gavriatopoulou M, Delimpasi S, Simonova M, Spicka I, Pour L, Dimopoulos MA, Kriachok I, Pylypenko H, Leleu X, Doronin V, Usenko G, Hajek R, Benjamin R, Dolai TK, Sinha DK, Venner CP, Garg M, Stevens DA, Quach H, Jagannath S, Moreau P, Levy M, Badros A, Anderson LD Jr, Bahlis NJ, Facon T, Mateos MV, Cavo M, Chai Y, Arazy M, Shah J, Shacham S, Kauffman MG, Richardson PG, Grosicki S. Effect of age and frailty on the efficacy and tolerability of once-weekly selinexor, bortezomib, and dexamethasone in previously treated multiple myeloma. Am J Hematol. 2021 Jun 1;96(6):708-718. doi: 10.1002/ajh.26172. Epub 2021 May 3.
• Grosicki S, Simonova M, Spicka I, Pour L, Kriachok I, Gavriatopoulou M, Pylypenko H, Auner HW, Leleu X, Doronin V, Usenko G, Bahlis NJ, Hajek R, Benjamin R, Dolai TK, Sinha DK, Venner CP, Garg M, Gironella M, Jurczyszyn A, Robak P, Galli M, Wallington-Beddoe C, Radinoff A, Salogub G, Stevens DA, Basu S, Liberati AM, Quach H, Goranova-Marinova VS, Bila J, Katodritou E, Oliynyk H, Korenkova S, Kumar J, Jagannath S, Moreau P, Levy M, White D, Gatt ME, Facon T, Mateos MV, Cavo M, Reece D, Anderson LD Jr, Saint-Martin JR, Jeha J, Joshi AA, Chai Y, Li L, Peddagali V, Arazy M, Shah J, Shacham S, Kauffman MG, Dimopoulos MA, Richardson PG, Delimpasi S. 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. Lancet. 2020 Nov 14;396(10262):1563-1573. doi: 10.1016/S0140-6736(20)32292-3.

Study record dates

Study Major Dates

• Study Start (Actual): May 24, 2017
• Primary Completion (Actual): February 18, 2020
• Study Completion (Actual): May 12, 2022

Study Registration Dates

• First Submitted: April 7, 2017
• First Submitted That Met QC Criteria: April 7, 2017
• First Posted (Actual): April 12, 2017

Study Record Updates

• Last Update Posted (Actual): August 21, 2024
• Last Update Submitted That Met QC Criteria: July 25, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Dexamethasone; Bortezomib; RRMM; Relapsed or Refractory Multiple Myeloma
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dexamethasone; Bortezomib
• Other Study ID Numbers: KCP-330-023

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No