BOSTON: Bortezomib, Selinexor, and Dexamethasone in Patients With Multiple Myeloma
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 Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 3 |
Study Design
Arms and Interventions
Arm | Intervention/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:
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:
Drug: Dexamethasone
oral dose of 20mg
|
Outcome Measures
Primary Outcome Measures
- 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
- 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)]
- Percentage of Participants With Response Rates [From date of randomization until disease progression or death, whichever occurred first (maximum duration up to 75 months)]
- Overall Survival (OS) [From date of randomization to the date of death or censored date, whichever occurred first (maximum duration of 75 months)]
- 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)]
- 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)]
- 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)]
- 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)]
- 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)]
- 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
Inclusion Criteria:
- 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.
-
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.
-
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.
-
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.
-
Must have an ECOG Status score of 0, 1, or 2.
-
Written informed consent in accordance with federal, local, and institutional guidelines.
-
Age ≥18 years.
-
Resolution of any clinically significant non-hematological toxicities (if any) from previous treatments to ≤ Grade 1 by C1D1.
-
Adequate hepatic function within 28 days prior to C1D1.
-
Adequate renal function within 28 days prior to C1D1.
-
Adequate hematopoietic function within 7 days prior to C1D1.
-
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:
-
Prior exposure to a SINE compound (i.e. an XPO-1 inhibitor), including selinexor.
-
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.
-
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.
-
Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within 1 week prior to C1D1.
-
Active plasma cell leukemia.
-
Documented systemic light chain amyloidosis.
-
MM involving the central nervous system.
-
Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome.
-
Spinal cord compression.
-
Greater than Grade 2 neuropathy or ≥ Grade 2 neuropathy with pain at baseline, regardless of whether or not the patient is currently receiving medication
-
Known intolerance, hypersensitivity, or contraindication to glucocorticoids.
-
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.
-
Prior autologous stem cell transplantation < 1 month or allogeneic stem cell transplantation < 4 months prior to C1D1.
-
Active graft versus host disease (after allogeneic stem cell transplantation) at C1D1.
-
Pregnant or breastfeeding females.
-
Body Surface Area < 1.4 m² at baseline, calculated by the Dubois or Mosteller method.
-
Life expectancy of < 4 months.
-
Major surgery within 4 weeks prior to C1D1.
-
Active, unstable cardiovascular function:
-
Symptomatic ischemia, or
-
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
-
Congestive heart failure of New York Heart Association Class ≥ 3 or known left ventricular ejection fraction < 40%, or
-
Myocardial infarction within 3 months prior to C1D1.
-
Known active human immunodeficiency virus (HIV) infection or HIV seropositivity
-
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.
-
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.
-
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.
-
Contraindication to any of the required concomitant drugs or supportive treatments.
-
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
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Boca Raton Clinical Research (BRCR) Medical Center | Plantation | Florida | United States | 33324 |
2 | Emory University | Atlanta | Georgia | United States | 30322 |
3 | Kaiser Permanente Hawaii | Honolulu | Hawaii | United States | 96817 |
4 | McFarland Clinic | Ames | Iowa | United States | 50010 |
5 | Stormont Vail Health Care (Cotton O'Neil Cancer Center ) | Topeka | Kansas | United States | 66606 |
6 | Commonwealth Hematology | Danville | Kentucky | United States | 40422 |
7 | Norton Cancer Institute | Louisville | Kentucky | United States | 40202 |
8 | University of Maryland | Baltimore | Maryland | United States | 21201 |
9 | Central Care Cancer Center | Bolivar | Missouri | United States | 65613 |
10 | The Valley Hospital Luckow Pavilion | Paramus | New Jersey | United States | 07652 |
11 | Mount Sinai | New York | New York | United States | 10029 |
12 | The Cancer Institute at St. Francis Hospital | Roslyn | New York | United States | 11576 |
13 | Novant-Forsyth Memorial Hospital | Winston-Salem | North Carolina | United States | 27103 |
14 | University of Cincinnati Health | Cincinnati | Ohio | United States | 45267 |
15 | Southwest Cancer Center of Oklahoma | Lawton | Oklahoma | United States | 73505 |
16 | Kaiser Permanente Northwest OR | Portland | Oregon | United States | 97210 |
17 | SCOR AnMed Health Cancer Center | Anderson | South Carolina | United States | 29621 |
18 | Prairie Lakes Healthcare | Watertown | South Dakota | United States | 57201 |
19 | Baylor Sammons Cancer Center | Dallas | Texas | United States | 75246 |
20 | University of Texas Southwestern | Dallas | Texas | United States | 75390 |
21 | Calvary Mater Newcastle | Waratah | New South Wales | Australia | 2298 |
22 | Royal Brisbane and Women's Hospital | Herston | Queensland | Australia | 4029 |
23 | Mater Misericordiae Limited and Mater Medical Research | South Brisbane | Queensland | Australia | 4101 |
24 | Gold Coast University Hospital | Southport | Queensland | Australia | 4215 |
25 | Royal Adelaide Hospital | Adelaide | South Australia | Australia | 5000 |
26 | Flinders Medical Centre | Bedford Park | South Australia | Australia | 5042 |
27 | St. Vincent's Hospital Melbourne | Fitzroy | Victoria | Australia | 3065 |
28 | The Alfred Hospital | Melbourne | Victoria | Australia | 3004 |
29 | Medical University Innsbruck, Department of Internal Medicine V (Hematology and Oncology) | Innsbruck | Austria | ||
30 | University Hospital Krems, Department of Internal Medicine II | Krems | Austria | ||
31 | Medical University of Vienna | Vienna | Austria | 1090 | |
32 | General Hospital Hietzing | Vienna | Austria | 1130 | |
33 | Wilhelminen Hospital, Department of Internal Medicine I, Center for Oncology & Hematology | Vienna | Austria | 1160 | |
34 | Jules Bordet Institute | Brussels | Belgium | 1000 | |
35 | UCL Saint-Luc | Brussels | Belgium | ||
36 | University Hospital Ghent | Ghent | Belgium | 9000 | |
37 | General Hospital Delta | Roeselare | Belgium | 8800 | |
38 | St. Augustinus Hospital | Wilrijk | Belgium | 2610 | |
39 | University Multiprofile Hospital for Active Treatment, Sveti Georgi Clinic of Clinical Hematology | Plovdiv | Bulgaria | 4002 | |
40 | University Multiprofile Hospital for Active Treatment, Sveti Ivan Rilski Clinic of Hematology | Sofia | Bulgaria | 1431 | |
41 | Specialized Hospital for Active Treatment of Hematological Diseases, Clinic of Hematology, Dept. of Clinical Hematology | Sofia | Bulgaria | 1756 | |
42 | Tom Baker Cancer Center/ Alberta Health Services | Calgary | Alberta | Canada | T2N 4Z6 |
43 | Cross Cancer Institute / University of Alberta | Edmonton | Alberta | Canada | T6G 1Z2 |
44 | Vancouver General Hospital | Vancouver | British Columbia | Canada | V5Z 1M9 |
45 | Queen Elizabeth II Health Sciences Center | Halifax | Nova Scotia | Canada | B3H 2Y9 |
46 | North East Cancer Centre Sudbury | Sudbury | Ontario | Canada | P3E 5J1 |
47 | Princess Margaret Cancer Research | Toronto | Ontario | Canada | M5G 1X5 |
48 | Maisonneuve-Rosemont Hospital | Montreal | Quebec | Canada | H1T 2M4 |
49 | Royal Victoria Hospital / McGill University | Montreal | Quebec | Canada | H3A 1A1 |
50 | L'Hôtel-Dieu de Québec | Quebec City | Quebec | Canada | G1R 2J6 |
51 | Saskatchewan Cancer Agency-Allan Blair Cancer Centre | Regina | Saskatchewan | Canada | S4T 7TI |
52 | Saskatoon Cancer Center | Saskatoon | Saskatchewan | Canada | S7N 4H4 |
53 | General University Hospital in Prague | Praha 2 | Prague | Czechia | 128 08 |
54 | University Hopsital Brno | Brno | Czechia | 625 00 | |
55 | University Hospital Hradec Kralove | Hradec Kralove | Czechia | 500 05 | |
56 | University Hospital Olomouc | Olomouc | Czechia | 775 20 | |
57 | University Hospital Ostrava, Dept. of Hematooncology | Ostrava | Czechia | 708 52 | |
58 | University Hospital Kralovske Vinohrady, Clinic of Internal Hematology | Prague | Czechia | 100 34 | |
59 | Necker Children's Hospital, Department of Adult Hematology | Paris | Ile De France | France | 75015 |
60 | Hospital Center Departmental La Roche-Sur-Yon | La Roche-sur-Yon | France | 85925 | |
61 | Claude Huriez Hospital | Lille | France | 59037 | |
62 | South Lyon Hospital Center | Lyon | France | 69002 | |
63 | Brabois Adults Hospital, University Hospital Center of Nancy | Nancy | France | 54511 | |
64 | Nantes University Hospital Center | Nantes | France | 44093 | |
65 | Saint-Louis Hospital | Paris | France | 75475 | |
66 | Miletrie Hospital, University Hospital Center of Poitiers | Poitiers | France | 86021 | |
67 | University Hospital Freiburg, Department of Internal Medicine I | Freiburg | Baden-Wuerttemberg | Germany | D-79106 |
68 | Klinikum Leverkusen gGmbH Medizinisxhe Klinik 3 | Leverkusen | North Rhine Westfalia | Germany | 51375 |
69 | Group Practice for Hematology and Oncology | Dresden | Saxony | Germany | 1307 |
70 | Alexandra General Hospital, Therapeutic Clinic | Athens | Greece | 11528 | |
71 | General Hospital of Athens "Evangelismos", Department of Hematology and Lymphoma | Athens | Greece | ||
72 | University General Hospital of Patra | Pátra | Greece | ||
73 | Theageneion Cancer Hospital, Hematology Department | Thessaloníki | Greece | 54639 | |
74 | Semmelweis University, 1st Department of Internal Medicine | Budapest | Hungary | H-1083 | |
75 | Integrated Szent Istvan and Szent laszlo Hospital, Department of Hematology and Stem Cell Transplantation | Budapest | Hungary | H-1097 | |
76 | Semmelweis University, 3rd Department of Internal Medicine | Budapest | Hungary | H-1125 | |
77 | Kaposi Mor Teaching Hospital, 2nd Department of Internal Medicine | Kaposvar | Hungary | 7400 | |
78 | Medical Center of the University of Pecs, Department of Hematology | Pecs | Hungary | 7624 | |
79 | Regional Cancer Centre | Patna | Bihar | India | 800014 |
80 | Regional Cancer Centre | Thiruvananthapuram | Kerala | India | 695011 |
81 | Prince Aly Khan Hospital | Mumbai | Maharashta | India | 400010 |
82 | Jaslok Hospital and Research Centre | Mumbai | Maharashta | India | 400026 |
83 | Bhaktivedanta Hospital | Thane | Maharashtra | India | 401107 |
84 | IMS & SUM Hospital | Bhubaneswar | Odisha | India | 751003 |
85 | Postgraduate Institute of Medical Education & Research (PGIMER) | Chandigarh | Punjab | India | 160012 |
86 | Dayanand Medical College & Hospital | Ludhiana | Punjab | India | 141001 |
87 | Cancer Institute | Chennai | Tamil Nadu | India | 600020 |
88 | SRM Institute of Medical Sciences | Chennai | Tamil Nadu | India | 600026 |
89 | Saveetha Medical College Hospital | Chennai | Tamil Nadu | India | 602105 |
90 | G. Kuppuswamy Naidu Hospital | Coimbatore | Tamil Nadu | India | 641037 |
91 | Asviratham Speciality Hospital | Madurai | Tamil Nadu | India | 625020 |
92 | Meenakshi Mission Hospital | Madurai | Tamil Nadu | India | 625107 |
93 | Yashoda Hospital | Hyderabad | Telengana | India | 500082 |
94 | King George's Medical University | Lucknow | Uttar Pradesh | India | 226003 |
95 | Netaji Subhash Chandra Bose Cancer Research Institute | Kolkata | West Bengal | India | 700094 |
96 | Nil Ratan Sircar (NRS) Medical College | Kolkata | West Bengal | India | 700120 |
97 | TATA Memorial Centre | Kolkata | West Bengal | India | 700160 |
98 | Rajiv Gandhi Cancer Hospital | New Delhi | India | 110085 | |
99 | Barzilai Medical Center | Ashkelon | Israel | 7830604 | |
100 | Rambam Health Care Campus | Haifa | Israel | 3109601 | |
101 | Hadassah Medical Center | Jerusalem | Israel | ||
102 | Rabin Medical Center | Petaẖ Tiqwa | Israel | 49100 | |
103 | Hospital Santa Maria of Terni | Terni | Umbria | Italy | 05100 |
104 | Azienda Ospedaliero-Universitaria Ospedali Riuniti | Ancona | Italy | 60131 | |
105 | ASST Papa Giovanni XXIII | Bergamo | Italy | 24127 | |
106 | Polyclinic S. Orsola-Malpighi, Department of Hematology, Oncology and Laboratory Medicine, Operative Unit of Hematology - Cavo | Bologna | Italy | 40138 | |
107 | University Hospital Careggi, Department of Hematology | Florence | Italy | 50134 | |
108 | University Hospital San Martino, IRCCA, Dept. of Integrative Cancer Therapies, Operative Unit of Clinical Hematology | Genoa | Italy | 16132 | |
109 | Hospital Niguerda Ca Granda, Department of Hematology and Oncology, Hematology Unit | Milan | Italy | 20162 | |
110 | Umberto I Polyclinic of Rome, Department of Cellular Biotechnology and Hematology, Hematology Center | Rome | Italy | 00161 | |
111 | University Hospital San Giovanni Battista of Turin | Turin | Italy | 10126 | |
112 | Jan Biziel University Hospital #2 in Bydgoszcz, Department of Hematology | Bydgoszcz | Poland | 85-168 | |
113 | Independent Public Healthcare Facility Municipal Hospital Group in Chorzow, Department of Hematology | Chorzow | Poland | 41-500 | |
114 | University Hospital in Krakow, Teaching Unit of the Hematology Department | Krakow | Poland | 31-501 | |
115 | Independent Public Teaching Hospital No.1 in Lublin, Department of Hematology-Oncology and Bone Marrow Transplantation | Lublin | Poland | 20-081 | |
116 | St. John of Dukla Oncology Center of Lublin, Department of Hematology | Lublin | Poland | 20-090 | |
117 | Military Institute of Medicine, Department of Internal Medicine and Hematology | Warsaw | Poland | 04-141 | |
118 | Nicolaus Copernicus Memorial Provincial Specialist Hospital in Lodz, Department of Hematology | Łódź | Poland | 93-513 | |
119 | Hyperclnical MedLife PDR Vulturului Brasov, Hematology Department | Braşov | Romania | 500366 | |
120 | Colentina Clinical Hospital, Department of Hematology | Bucharest | Romania | 020125 | |
121 | Bucharest University Emergency Hospital, Department of Hematology | Bucharest | Romania | 050098 | |
122 | S.P. Botkin City Clinical Hospital | Moscow | Russian Federation | 125284 | |
123 | N.A. Semashko Central Clinical Hospital #2 under OJSC Russian Railways | Moscow | Russian Federation | 129128 | |
124 | First I.P. Pavlov State Medical University of St. Petersburg | Saint Petersburg | Russian Federation | 197022 | |
125 | V.A. Almazov North-West Federal Medical Research Center, Chemotherapy of Oncohematology Diseases and Bone Marrow Transplantation Department #1 | Saint Petersburg | Russian Federation | 197341 | |
126 | Clinical Center of Serbia, Clinic of Hematology | Belgrade | Serbia | 11000 | |
127 | Institute of Oncology and Radiology of Serbia, Clinic of Medical Oncology | Belgrade | Serbia | 11000 | |
128 | Clinical Center Kragujevac, Clinic of Hematology | Kragujevac | Serbia | 34 000 | |
129 | Clinical Center Nis, Clinic of Hematology and Clinical Immunology | Nis | Serbia | 18 000 | |
130 | Clinical Center of Vojvodina, Clinic of Hematology | Novi Sad | Serbia | 21 000 | |
131 | University Hospital of the Canary Islands | La Laguna | Santa Cruz De Tenerife | Spain | 38320 |
132 | Catalan Institute of Oncology (ICO) Badalona | Badalona | Spain | 08916 | |
133 | University Hospital of Vall d'Hebron | Barcelona | Spain | 08035 | |
134 | University Hospital Infanta Leonor, Department of Hematology | Madrid | Spain | 28301 | |
135 | University Clinical Hospital of Salamanca, Department of Hematology | Salamanca | Spain | 37007 | |
136 | University Hospital Virgen del Rocio (HUVR) | Seville | Spain | 41013 | |
137 | Cherkasy Regional Oncology Center, Regional Treatment and Diagnostic Hematology Center, Department of Hematology | Cherkasy | Ukraine | 18009 | |
138 | City Clinical Hospital No.4 of Dnipro City Council, City hematology center | Dnipropetrovsk | Ukraine | ||
139 | BMT Kiev Center | Kiev | Ukraine | ||
140 | Kiev Cancer Institute | Kiev | Ukraine | ||
141 | Institute of Blood Pathology and Transfusion Medicine, Department of Hematology with Laboratory Group | Lviv | Ukraine | 79044 | |
142 | Vinnytsia M.I. Pyrohov Regional Clinical Hospital, Department of Hematology | Vinnytsia | Ukraine | 21018 | |
143 | O.F. Herbachevskyi Regional Clinical Hospital, Hematology Department with Intensive Therapy Wards | Zhytomyr | Ukraine | 10008 | |
144 | Belfast Heatlh & Social Care Trust Belfast City Hospital | Belfast | Northern Ireland | United Kingdom | BT9 7AB |
145 | NHS Tayside Ninewells Hospital | Dundee | Scotland | United Kingdom | DD1 9SY |
146 | Cardiff & Vale University Health Board University Hospital of Wales | Cardiff | Wales | United Kingdom | CF14 4XW |
147 | University Hospitals Birmingham NHS Foundation Trust Queen Elizabeth Hospital | Birmingham | United Kingdom | B15 2TH | |
148 | The Leeds Teaching Hospitals NHS Trust St. James University Hospital | Leeds | United Kingdom | LS9 7TF | |
149 | University Hospitals of Leicester NHS Trust Royal Leicester Infirmary | Leicester | United Kingdom | LE1 5WW | |
150 | Royal Liverpool & Broadgreen University Hospital NHS Trust Royal Liverpool University Hospital | Liverpool | United Kingdom | L7 8XP | |
151 | London North West Healthcare NHS Trust Northwick Park Hospital | London | United Kingdom | HA1 3UJ | |
152 | University College London | London | United Kingdom | NW3 2PF | |
153 | King's College Hospital NHS Foundation Trust | London | United Kingdom | SE5 9RS | |
154 | Imperial College Healthcare NHS Trust Hammersmith Hospital | London | United Kingdom | W12 0HS | |
155 | The Christie NHS Foundation Trust | Manchester | United Kingdom | M20 4BX | |
156 | Freeman Hospital | Newcastle Upon Tyne | United Kingdom | NE7 7DN | |
157 | The Royal Wolverhampton NHS Trust New Cross Hospital | Wolverhampton | United Kingdom | WV10 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.- KCP-330-023
Study Results
Participant Flow
Recruitment Details | The study was conducted at 165 sites in 21 countries. |
---|---|
Pre-assignment Detail | A 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 Title | SVd Arm: Selinexor + Bortezomib + Dexamethasone | Vd Arm: Bortezomib + Dexamethasone |
---|---|---|
Arm/Group Description | 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. | 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 | ||
STARTED | 195 | 207 |
Treated | 195 | 204 |
COMPLETED | 0 | 0 |
NOT COMPLETED | 195 | 207 |
Baseline Characteristics
Arm/Group Title | SVd Arm: Selinexor + Bortezomib + Dexamethasone | Vd Arm: Bortezomib + Dexamethasone | Total |
---|---|---|---|
Arm/Group Description | Participants 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 Participants | 195 | 207 | 402 |
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
Title | Progression-free Survival (PFS) as Assessed by IRC |
---|---|
Description | 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%). |
Time Frame | From 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 Title | SVd Arm: Selinexor + Bortezomib + Dexamethasone | Vd Arm: Bortezomib + Dexamethasone |
---|---|---|
Arm/Group Description | Participants 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 Participants | 80 | 124 |
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 Hypothesis | p-Value | 0.0075 |
Comments | ||
Method | Stratified Log-rank Test | |
Comments | ||
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 0.7020 | |
Confidence Interval |
(2-Sided) 95% 0.5279 to 0.9335 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Overall Response Rate (ORR) as Assessed by IRC |
---|---|
Description | |
Time Frame | From 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 |
Title | Percentage of Participants With Response Rates |
---|---|
Description | |
Time Frame | From 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 |
Title | Overall Survival (OS) |
---|---|
Description | |
Time Frame | From 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 |
Title | Duration of Response (DOR) as Assessed by IRC |
---|---|
Description | |
Time Frame | 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) |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title |
---|
Arm/Group Description |
Title | Time-to-next-treatment (TTNT) |
---|---|
Description | |
Time Frame | From 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 |
Title | Time-to-response (TTR) as Assessed by IRC |
---|---|
Description | |
Time Frame | From 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 |
Title | Number of Participants With Grade >= 2 Peripheral Neuropathy Events |
---|---|
Description | |
Time Frame | From 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 |
Title | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs |
---|---|
Description | |
Time Frame | From 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 |
Title | Patient-reported Peripheral Neuropathy Measured by European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-CIPN20 Instrument |
---|---|
Description | |
Time Frame | Up to 75 months |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title |
---|
Arm/Group Description |
Adverse Events
Time Frame | From date of randomization up to 30 days after last dose of treatment (up to 32 months ) | |||
---|---|---|---|---|
Adverse Event Reporting Description | ||||
Arm/Group Title | SVd Arm: Selinexor + Bortezomib + Dexamethasone | Vd Arm: Bortezomib + Dexamethasone | ||
Arm/Group Description | Participants 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 + Dexamethasone | Vd Arm: Bortezomib + Dexamethasone | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 47/195 (24.1%) | 61/204 (29.9%) | ||
Serious Adverse Events |
||||
SVd Arm: Selinexor + Bortezomib + Dexamethasone | Vd Arm: Bortezomib + Dexamethasone | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 101/195 (51.8%) | 77/204 (37.7%) | ||
Blood and lymphatic system disorders | ||||
Anaemia | 5/195 (2.6%) | 3/204 (1.5%) | ||
Thrombocytopenia | 3/195 (1.5%) | 1/204 (0.5%) | ||
Febrile neutropenia | 1/195 (0.5%) | 1/204 (0.5%) | ||
Neutropenia | 1/195 (0.5%) | 0/204 (0%) | ||
Cardiac disorders | ||||
Atrial fibrillation | 4/195 (2.1%) | 2/204 (1%) | ||
Cardiac failure congestive | 1/195 (0.5%) | 1/204 (0.5%) | ||
Myocardial infarction | 1/195 (0.5%) | 1/204 (0.5%) | ||
Acute myocardial infarction | 0/195 (0%) | 1/204 (0.5%) | ||
Angina pectoris | 0/195 (0%) | 1/204 (0.5%) | ||
Atrioventricular block | 1/195 (0.5%) | 0/204 (0%) | ||
Bradycardia | 1/195 (0.5%) | 0/204 (0%) | ||
Cardiac arrest | 1/195 (0.5%) | 0/204 (0%) | ||
Cardiac failure | 0/195 (0%) | 1/204 (0.5%) | ||
Cardio-respiratory arrest | 1/195 (0.5%) | 0/204 (0%) | ||
Cardiomyopathy | 0/195 (0%) | 1/204 (0.5%) | ||
Cardiovascular disorder | 1/195 (0.5%) | 0/204 (0%) | ||
Left ventricular dysfunction | 1/195 (0.5%) | 0/204 (0%) | ||
Left ventricular failure | 0/195 (0%) | 1/204 (0.5%) | ||
Myocardial ischaemia | 0/195 (0%) | 1/204 (0.5%) | ||
Sinus tachycardia | 1/195 (0.5%) | 0/204 (0%) | ||
Ventricular arrhythmia | 1/195 (0.5%) | 0/204 (0%) | ||
Eye disorders | ||||
Cataract | 4/195 (2.1%) | 0/204 (0%) | ||
Gastrointestinal disorders | ||||
Diarrhoea | 7/195 (3.6%) | 0/204 (0%) | ||
Vomiting | 7/195 (3.6%) | 0/204 (0%) | ||
Nausea | 4/195 (2.1%) | 0/204 (0%) | ||
Constipation | 1/195 (0.5%) | 2/204 (1%) | ||
Abdominal pain | 0/195 (0%) | 2/204 (1%) | ||
Colitis | 1/195 (0.5%) | 0/204 (0%) | ||
Colitis ischaemic | 1/195 (0.5%) | 0/204 (0%) | ||
Dyspepsia | 0/195 (0%) | 1/204 (0.5%) | ||
Lower gastrointestinal haemorrhage | 1/195 (0.5%) | 0/204 (0%) | ||
General disorders | ||||
Asthenia | 2/195 (1%) | 2/204 (1%) | ||
Pyrexia | 3/195 (1.5%) | 1/204 (0.5%) | ||
Fatigue | 2/195 (1%) | 1/204 (0.5%) | ||
General physical health deterioration | 3/195 (1.5%) | 0/204 (0%) | ||
Chest pain | 1/195 (0.5%) | 1/204 (0.5%) | ||
Death | 1/195 (0.5%) | 0/204 (0%) | ||
Multiple organ dysfunction syndrome | 1/195 (0.5%) | 0/204 (0%) | ||
Non-cardiac chest pain | 1/195 (0.5%) | 0/204 (0%) | ||
Hepatobiliary disorders | ||||
Cholecystitis acute | 1/195 (0.5%) | 0/204 (0%) | ||
Cholelithiasis | 1/195 (0.5%) | 0/204 (0%) | ||
Hepatic cirrhosis | 0/195 (0%) | 1/204 (0.5%) | ||
Liver disorder | 1/195 (0.5%) | 0/204 (0%) | ||
Infections and infestations | ||||
Pneumonia | 23/195 (11.8%) | 24/204 (11.8%) | ||
Lower respiratory tract infection | 4/195 (2.1%) | 3/204 (1.5%) | ||
Bronchitis | 3/195 (1.5%) | 2/204 (1%) | ||
Gastroenteritis | 4/195 (2.1%) | 1/204 (0.5%) | ||
Influenza | 3/195 (1.5%) | 1/204 (0.5%) | ||
Septic shock | 4/195 (2.1%) | 0/204 (0%) | ||
Upper respiratory tract infection | 3/195 (1.5%) | 1/204 (0.5%) | ||
Urinary tract infection | 4/195 (2.1%) | 0/204 (0%) | ||
Respiratory syncytial virus infection | 2/195 (1%) | 1/204 (0.5%) | ||
Urosepsis | 3/195 (1.5%) | 0/204 (0%) | ||
Cellulitis | 1/195 (0.5%) | 1/204 (0.5%) | ||
Clostridium difficile colitis | 0/195 (0%) | 2/204 (1%) | ||
Infection | 1/195 (0.5%) | 1/204 (0.5%) | ||
Pneumonia pneumococcal | 2/195 (1%) | 0/204 (0%) | ||
Staphylococcal sepsis | 1/195 (0.5%) | 1/204 (0.5%) | ||
Chest wall abscess | 0/195 (0%) | 1/204 (0.5%) | ||
Clostridium difficile infection | 1/195 (0.5%) | 0/204 (0%) | ||
Corona virus infection | 1/195 (0.5%) | 0/204 (0%) | ||
Escherichia bacteraemia | 1/195 (0.5%) | 0/204 (0%) | ||
Gangrene | 0/195 (0%) | 1/204 (0.5%) | ||
Gastroenteritis norovirus | 1/195 (0.5%) | 0/204 (0%) | ||
H1N1 influenza | 0/195 (0%) | 1/204 (0.5%) | ||
Laryngitis | 0/195 (0%) | 1/204 (0.5%) | ||
Meningitis tuberculous | 1/195 (0.5%) | 0/204 (0%) | ||
Orchitis | 1/195 (0.5%) | 0/204 (0%) | ||
Pneumonia bacterial | 1/195 (0.5%) | 0/204 (0%) | ||
Pneumonia fungal | 1/195 (0.5%) | 0/204 (0%) | ||
Pneumonia influenzal | 1/195 (0.5%) | 0/204 (0%) | ||
Pneumonia parainfluenzae viral | 1/195 (0.5%) | 0/204 (0%) | ||
Pneumonia respiratory syncytial viral | 0/195 (0%) | 1/204 (0.5%) | ||
Pulmonary sepsis | 0/195 (0%) | 1/204 (0.5%) | ||
Sepsis | 1/195 (0.5%) | 0/204 (0%) | ||
Injury, poisoning and procedural complications | ||||
Femur fracture | 2/195 (1%) | 1/204 (0.5%) | ||
Fall | 2/195 (1%) | 0/204 (0%) | ||
Cervical vertebral fracture | 0/195 (0%) | 1/204 (0.5%) | ||
Femoral neck fracture | 0/195 (0%) | 1/204 (0.5%) | ||
Hip fracture | 1/195 (0.5%) | 0/204 (0%) | ||
Injury | 1/195 (0.5%) | 0/204 (0%) | ||
Overdose | 1/195 (0.5%) | 0/204 (0%) | ||
Pelvic fracture | 1/195 (0.5%) | 0/204 (0%) | ||
Postoperative respiratory failure | 1/195 (0.5%) | 0/204 (0%) | ||
Rib fracture | 1/195 (0.5%) | 0/204 (0%) | ||
Subdural haemorrhage | 0/195 (0%) | 1/204 (0.5%) | ||
Investigations | ||||
Blood glucose abnormal | 1/195 (0.5%) | 0/204 (0%) | ||
Metabolism and nutrition disorders | ||||
Dehydration | 3/195 (1.5%) | 0/204 (0%) | ||
Hypokalaemia | 1/195 (0.5%) | 1/204 (0.5%) | ||
Cachexia | 1/195 (0.5%) | 0/204 (0%) | ||
Decreased appetite | 1/195 (0.5%) | 0/204 (0%) | ||
Hyperkalaemia | 0/195 (0%) | 1/204 (0.5%) | ||
Tumour lysis syndrome | 0/195 (0%) | 1/204 (0.5%) | ||
Musculoskeletal and connective tissue disorders | ||||
Bone pain | 1/195 (0.5%) | 1/204 (0.5%) | ||
Back pain | 0/195 (0%) | 1/204 (0.5%) | ||
Mobility decreased | 1/195 (0.5%) | 0/204 (0%) | ||
Osteoarthritis | 1/195 (0.5%) | 0/204 (0%) | ||
Osteochondrosis | 0/195 (0%) | 1/204 (0.5%) | ||
Spinal pain | 1/195 (0.5%) | 0/204 (0%) | ||
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
Myelodysplastic syndrome | 0/195 (0%) | 1/204 (0.5%) | ||
Ovarian neoplasm | 0/195 (0%) | 1/204 (0.5%) | ||
Pancreatic carcinoma metastatic | 0/195 (0%) | 1/204 (0.5%) | ||
Nervous system disorders | ||||
Cerebral infarction | 0/195 (0%) | 2/204 (1%) | ||
Neuropathy peripheral | 0/195 (0%) | 2/204 (1%) | ||
Syncope | 1/195 (0.5%) | 1/204 (0.5%) | ||
Transient ischaemic attack | 1/195 (0.5%) | 1/204 (0.5%) | ||
Brain oedema | 1/195 (0.5%) | 0/204 (0%) | ||
Carotid artery aneurysm | 1/195 (0.5%) | 0/204 (0%) | ||
Cerebral haemorrhage | 1/195 (0.5%) | 0/204 (0%) | ||
Cerebral ischaemia | 1/195 (0.5%) | 0/204 (0%) | ||
Dementia Alzheimer's type | 1/195 (0.5%) | 0/204 (0%) | ||
Encephalopathy | 1/195 (0.5%) | 0/204 (0%) | ||
Hepatic encephalopathy | 0/195 (0%) | 1/204 (0.5%) | ||
Ischaemic stroke | 0/195 (0%) | 1/204 (0.5%) | ||
Metabolic encephalopathy | 1/195 (0.5%) | 0/204 (0%) | ||
Neuralgia | 0/195 (0%) | 1/204 (0.5%) | ||
Paraesthesia | 0/195 (0%) | 1/204 (0.5%) | ||
Presyncope | 0/195 (0%) | 1/204 (0.5%) | ||
Vascular dementia | 1/195 (0.5%) | 0/204 (0%) | ||
Psychiatric disorders | ||||
Affect lability | 1/195 (0.5%) | 0/204 (0%) | ||
Mixed anxiety and depressive disorder | 1/195 (0.5%) | 0/204 (0%) | ||
Personality change | 1/195 (0.5%) | 0/204 (0%) | ||
Reactive psychosis | 1/195 (0.5%) | 0/204 (0%) | ||
Renal and urinary disorders | ||||
Acute kidney injury | 4/195 (2.1%) | 2/204 (1%) | ||
Haematuria | 1/195 (0.5%) | 0/204 (0%) | ||
Reproductive system and breast disorders | ||||
Pelvic prolapse | 1/195 (0.5%) | 0/204 (0%) | ||
Respiratory, thoracic and mediastinal disorders | ||||
Chronic obstructive pulmonary disease | 1/195 (0.5%) | 2/204 (1%) | ||
Dyspnoea | 2/195 (1%) | 1/204 (0.5%) | ||
Epistaxis | 3/195 (1.5%) | 0/204 (0%) | ||
Pulmonary embolism | 2/195 (1%) | 1/204 (0.5%) | ||
Pulmonary oedema | 1/195 (0.5%) | 1/204 (0.5%) | ||
Acute respiratory failure | 1/195 (0.5%) | 0/204 (0%) | ||
Bronchiectasis | 1/195 (0.5%) | 0/204 (0%) | ||
Bronchospasm | 1/195 (0.5%) | 0/204 (0%) | ||
Pneumonitis | 1/195 (0.5%) | 0/204 (0%) | ||
Vascular disorders | ||||
Deep vein thrombosis | 1/195 (0.5%) | 2/204 (1%) | ||
Blood pressure fluctuation | 1/195 (0.5%) | 0/204 (0%) | ||
Circulatory collapse | 0/195 (0%) | 1/204 (0.5%) | ||
Embolism | 0/195 (0%) | 1/204 (0.5%) | ||
Hypotension | 1/195 (0.5%) | 0/204 (0%) | ||
Orthostatic hypotension | 0/195 (0%) | 1/204 (0.5%) | ||
Peripheral ischaemia | 0/195 (0%) | 1/204 (0.5%) | ||
Shock haemorrhagic | 1/195 (0.5%) | 0/204 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
SVd Arm: Selinexor + Bortezomib + Dexamethasone | Vd Arm: Bortezomib + Dexamethasone | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 193/195 (99%) | 197/204 (96.6%) | ||
Blood and lymphatic system disorders | ||||
Thrombocytopenia | 116/195 (59.5%) | 55/204 (27%) | ||
Anaemia | 71/195 (36.4%) | 45/204 (22.1%) | ||
Neutropenia | 29/195 (14.9%) | 12/204 (5.9%) | ||
Leukopenia | 10/195 (5.1%) | 3/204 (1.5%) | ||
Lymphopenia | 11/195 (5.6%) | 4/204 (2%) | ||
Cardiac disorders | ||||
Tachycardia | 10/195 (5.1%) | 3/204 (1.5%) | ||
Eye disorders | ||||
Cataract | 39/195 (20%) | 13/204 (6.4%) | ||
Vision blurred | 13/195 (6.7%) | 8/204 (3.9%) | ||
Visual impairment | 11/195 (5.6%) | 4/204 (2%) | ||
Gastrointestinal disorders | ||||
Nausea | 98/195 (50.3%) | 20/204 (9.8%) | ||
Diarrhoea | 60/195 (30.8%) | 51/204 (25%) | ||
Constipation | 33/195 (16.9%) | 34/204 (16.7%) | ||
Vomiting | 39/195 (20%) | 9/204 (4.4%) | ||
Abdominal pain | 15/195 (7.7%) | 11/204 (5.4%) | ||
General disorders | ||||
Fatigue | 82/195 (42.1%) | 37/204 (18.1%) | ||
Asthenia | 47/195 (24.1%) | 25/204 (12.3%) | ||
Oedema peripheral | 23/195 (11.8%) | 26/204 (12.7%) | ||
Pyrexia | 28/195 (14.4%) | 21/204 (10.3%) | ||
Infections and infestations | ||||
Upper respiratory tract infection | 32/195 (16.4%) | 29/204 (14.2%) | ||
Bronchitis | 21/195 (10.8%) | 18/204 (8.8%) | ||
Nasopharyngitis | 23/195 (11.8%) | 10/204 (4.9%) | ||
Pneumonia | 12/195 (6.2%) | 9/204 (4.4%) | ||
Urinary tract infection | 12/195 (6.2%) | 9/204 (4.4%) | ||
Lower respiratory tract infection | 12/195 (6.2%) | 8/204 (3.9%) | ||
Investigations | ||||
Weight decreased | 51/195 (26.2%) | 25/204 (12.3%) | ||
Alanine aminotransferase increased | 13/195 (6.7%) | 7/204 (3.4%) | ||
Metabolism and nutrition disorders | ||||
Decreased appetite | 69/195 (35.4%) | 11/204 (5.4%) | ||
Hypokalaemia | 18/195 (9.2%) | 9/204 (4.4%) | ||
Hyperglycaemia | 14/195 (7.2%) | 11/204 (5.4%) | ||
Hypophosphataemia | 16/195 (8.2%) | 6/204 (2.9%) | ||
Hypercreatininaemia | 13/195 (6.7%) | 7/204 (3.4%) | ||
Hypocalcaemia | 15/195 (7.7%) | 5/204 (2.5%) | ||
Hyponatraemia | 15/195 (7.7%) | 3/204 (1.5%) | ||
Musculoskeletal and connective tissue disorders | ||||
Back pain | 30/195 (15.4%) | 28/204 (13.7%) | ||
Pain in extremity | 9/195 (4.6%) | 17/204 (8.3%) | ||
Arthralgia | 8/195 (4.1%) | 12/204 (5.9%) | ||
Muscle spasms | 3/195 (1.5%) | 12/204 (5.9%) | ||
Nervous system disorders | ||||
Neuropathy peripheral | 63/195 (32.3%) | 96/204 (47.1%) | ||
Dizziness | 24/195 (12.3%) | 8/204 (3.9%) | ||
Headache | 19/195 (9.7%) | 11/204 (5.4%) | ||
Paraesthesia | 5/195 (2.6%) | 15/204 (7.4%) | ||
Dysgeusia | 13/195 (6.7%) | 1/204 (0.5%) | ||
Psychiatric disorders | ||||
Insomnia | 31/195 (15.9%) | 32/204 (15.7%) | ||
Confusional state | 16/195 (8.2%) | 2/204 (1%) | ||
Respiratory, thoracic and mediastinal disorders | ||||
Cough | 35/195 (17.9%) | 30/204 (14.7%) | ||
Dyspnoea | 18/195 (9.2%) | 26/204 (12.7%) | ||
Dyspnoea exertional | 10/195 (5.1%) | 8/204 (3.9%) | ||
Oropharyngeal pain | 12/195 (6.2%) | 4/204 (2%) | ||
Epistaxis | 10/195 (5.1%) | 3/204 (1.5%) | ||
Vascular disorders | ||||
Hypertension | 17/195 (8.7%) | 16/204 (7.8%) | ||
Hypotension | 10/195 (5.1%) | 11/204 (5.4%) |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Results Point of Contact
Name/Title | Jatin Shah, MD |
---|---|
Organization | Karyopharm Therapeutics Inc. |
Phone | (617) 658-0600 |
jshah@karyopharm.com |
- KCP-330-023