STORM: Selinexor Treatment of Refractory Myeloma
Sponsor
Karyopharm Therapeutics Inc (Industry)
Overall Status
Completed
CT.gov ID
NCT02336815
Collaborator
(none)
202
61
2
50
3.3
0.1
Study Details
Study Description
Brief Summary
This is a Phase 2b, single-arm, open-label, multicenter study of selinexor 80 mg plus dexamethasone 20 mg (Sd) dosed twice weekly in four-week cycles, in patients with penta-refractory MM (Parts 1 and 2) or quad refractory MM (Part 1 only).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
This is a Phase 2b, single-arm, open-label, multicenter study of selinexor 80 mg plus dexamethasone 20 mg (Sd), both dosed twice weekly in each four-week cycle, in patients with MM previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, and daratumumab and refractory to prior treatment with glucocorticoids, an immunomodulatory agent (IMiD), a proteasome inhibitor (PI), and daratumumab.
This study consists of two parts:
-
Part 1 enrolled patients with both quad-refractory MM and penta-refractory MM.
-
Part 2 will enroll patients with penta-refractory MM only.
Study Design
Study Type:
Interventional
Actual Enrollment
:
202 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 2b, Open-Label, Single-Arm Study of Selinexor (KPT-330) Plus Low-Dose Dexamethasone (Sd) in Patients With Multiple Myeloma Previously Treated With Lenalidomide, Pomalidomide, Bortezomib, Carfilzomib, and an Anti-CD38 Monoclonal Antibody (mAb) Daratumumab, and Refractory to Prior Treatment With Glucocorticoids, an Immunomodulatory Agent, a Proteasome Inhibitor, and an the Anti-CD38 mAb Daratumumab
Actual Study Start Date
:
May 26, 2015
Actual Primary Completion Date
:
Jul 26, 2019
Actual Study Completion Date
:
Jul 26, 2019
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Part 1 Participants with quad-exposed, double-class-refractory (i.e. previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, but not an anti-CD38 mab) and penta-exposed, triple-class-refractory multiple myeloma (MM) (i.e. previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, and daratumumab, and refractory to prior treatment with glucocorticoids, an immunomodulatory agent (IMiD), a proteasome inhibitor (PI), and the anti-CD38 mAb daratumumab) received, two dosing schedules (1) Selinexor 80 milligrams (mg) plus low-dose dexamethasone 20 mg (Sd) twice-weekly on Days 1 and 3 for 3 weeks of each 4-week cycle (2) Selinexor 80 mg plus low-dose dexamethasone 20 mg (Sd) twice-weekly continuously in 4-week cycles; until disease progression, death, or unacceptable toxicity (maximum duration of approximately 13 months). |
Drug: Selinexor
Fixed oral dose of 80 mg twice weekly (e.g., Monday and Wednesday or Tuesday and Thursday, etc.)
Other Names:
Drug: Dexamethasone
20 mg was given with each dose of Selinexor.
|
| Experimental: Part 2 Participants who previously had received more than 3 anti-MM regimens and had penta-exposed, triple class-refractory MM (i.e. previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, and daratumumab, and refractory to prior treatment with glucocorticoids, an IMiD, a PI, and the anti-CD38 mAb daratumumab) received, Selinexor 80 mg post oral (PO) plus low-dose dexamethasone 20 mg Sd twice-weekly on Days 1 and 3 until disease progression, death, or unacceptable toxicity (maximum duration of approximately 17 months). |
Drug: Selinexor
Fixed oral dose of 80 mg twice weekly (e.g., Monday and Wednesday or Tuesday and Thursday, etc.)
Other Names:
Drug: Dexamethasone
20 mg was given with each dose of Selinexor.
|
Outcome Measures
Primary Outcome Measures
- Part 2: Percentage of Participants With Overall Response Rate (ORR) Per International MyelomaWorking Group (IMWG) as Assessed by an Independent Review Committee (IRC) [Baseline until disease progression/discontinuation from the study, or death, whichever occurred first (maximum duration of 17 months)]
IRC assessed ORR per 2016 IMWG criteria: Percentage of participants who experienced Partial response (PR): greater than or equal to (>=) 50 percent (%) reduction of serum M-Protein and reduction in 24-hour urinary M-protein by >= 90% or to lesser than (<) 200 mg per 24 hours; Very good partial response (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; Complete response (CR): Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and lesser than or equal to (<=) 5% plasma cells in bone marrow; or stringent complete response (sCR): CR as defined+Normal free light chain (FLC) ratio+Absence of clonal cells in bone marrow biopsy by immunohistochemistry).
Secondary Outcome Measures
- Part 1: Duration of Response (DoR) Per IMWG as Assessed by IRC [First response subsequently confirmed to disease progression/discontinuation from the study, or death, whichever occurred first (maximum duration of 13 months)]
IRC assessed DoR per 2016 IMWG criteria: time (in months) from the first documentation of objective response (confirmed CR or PR) to the date of first documentation of progressive disease (PD) or death due to any cause. Partial response (PR): >= 50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by >= 90% or to < 200 mg per 24 hours; Complete response (CR): Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and <= 5% plasma cells in bone marrow; Progressive disease (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 gram per deciliter (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.
- Part 2: Duration of Response (DoR) Per IMWG as Assessed by an IRC [First response subsequently confirmed to disease progression/discontinuation from the study, or death, whichever occurred first (maximum duration of 17 months)]
IRC assessed DoR per 2016 IMWG criteria: time (in months) from the first documentation of objective response (confirmed CR or PR) to the date of first documentation of progressive disease (PD) or death due to any cause. Partial response (PR): >= 50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by >= 90% or to < 200 mg per 24 hours; Complete response (CR): Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and <= 5% plasma cells in bone marrow; Progressive disease (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.
- Part 1: Percentage of Participants With Clinical Benefit Rate (CBR) ) Per IMWG as Assessed by IRC [Baseline up to a maximum of 13 months]
IRC assessed CBR per 2016 IMWG criteria: Percentage of participants with a confirmed minimal response (MR) or better (PR, VGPR, CR or sCR) before confirmed disease progression or initiating new MM treatment. Minimal response (MR): >= 25% but < 49% reduction of serum M-protein and reduction in 24-hour urinary M-protein by 50-89%. Partial response (PR): >= 50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by >= 90% or to < 200 mg per 24 hours; Very good partial response (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; Complete response (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+Normal free light chain (FLC) ratio+Absence of clonal cells by immunohistochemistry).
- Part 2: Percentage of Participants With Clinical Benefit Rate (CBR) Per IMWG as Assessed by IRC [Baseline up to a maximum of 17 months]
IRC assessed CBR per 2016 IMWG criteria: Percentage of participants with a confirmed minimal response (MR) or better (PR, VGPR, CR or sCR) before confirmed disease progression or initiating new MM treatment. Minimal response (MR): >= 25% but < 49% reduction of serum M-protein and reduction in 24-hour urinary M-protein by 50-89%. Partial response (PR): >= 50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by >= 90% or to < 200 mg per 24 hours; Very good partial response (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; Complete response (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+Normal free light chain (FLC) ratio+Absence of clonal cells by immunohistochemistry).
- Part 1: Duration of Clinical Benefit Per IMWG as Assessed by IRC [First response subsequently confirmed to disease progression, or death, whichever occurred first (maximum duration of 13 months)]
IRC assessed duration of clinical benefit per 2016 IMWG criteria: Duration from first response (at least MR) to time of IRC-determined PD or death due to disease progression, whichever occurs first. Minimal response (MR): >= 25% but < 49% reduction of serum M-protein and reduction in 24-hour urinary M-protein by 50-89%. Progressive disease (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; Urinary M-protein (absolute increase must be >= 200 mg per 24 hours). Analysis was performed using Kaplan-Meier method.
- Part 2: Duration of Clinical Benefit Per IMWG as Assessed by IRC [First response subsequently confirmed to disease progression, or death, whichever occurred first (maximum duration of 17 months)]
IRC assessed duration of clinical benefit per 2016 IMWG criteria: Duration from first response (at least MR) to time of IRC-determined PD or death due to disease progression, whichever occurs first. Minimal response (MR): >= 25% but < 49% reduction of serum M-protein and reduction in 24-hour urinary M-protein by 50-89%. Progressive disease (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; Urinary M-protein (absolute increase must be >= 200 mg per 24 hours). Analysis was performed using Kaplan-Meier method.
- Part 2: Disease Control Rate (DCR) [Every 12 weeks until progressive disease or death due to any cause, up to 17 months]
DCR was defined as the percentage of participants who achieved stable disease (SD) or better (MR, PR, VGPR, CR, sCR) for a minimum of 12 weeks. Stable disease (SD): Not recommended for use as an indicator of response; stability of disease was best described by providing the time to progression (TTP) estimates. MR: >= 25% but < 49% reduction of serum M-protein and reduction in 24-hour urinary M-protein by 50-89%. 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: CR as defined+Normal FLC ratio+Absence of clonal cells by immunohistochemistry).
- Part 1: Progression Free Survival (PFS) Per IMWG as Assessed by IRC [From start of study treatment to progression of disease or discontinuation from the study or death, whichever occurred first (maximum duration of 13 months)]
IRC assessed PFS per 2016 IMWG criteria: Duration from start of study treatment until IRC-determined progressive disease (PD) or death from any cause, whichever occurred first. Progressive disease (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; Urinary M-protein (absolute increase must be >= 200 mg/24 hours). Analysis was performed using Kaplan-Meier method.
- Part 2: Progression Free Survival (PFS) Per IMWG as Assessed by IRC [From start of study treatment to progression of disease or discontinuation from the study or death, whichever occurred first (maximum duration of 17 months)]
IRC assessed PFS per 2016 IMWG criteria: Duration from start of study treatment until IRC-determined progressive disease (PD) or death from any cause, whichever occurred first. Progressive disease (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; Urinary M-protein (absolute increase must be >= 200 mg/24 hours). Analysis was performed using Kaplan-Meier method.
- Part 1: Time to Progression (TTP) Per IMWG as Assessed by IRC [From start of study treatment to progression of disease or death, whichever occurred first (maximum duration of 13 months)]
IRC assessed TTP per 2016 IMWG criteria: Duration from start of study treatment until PD or death due to PD (per IRC), whichever occurred first. Progressive disease (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; Urinary M-protein (absolute increase must be >= 200 mg/24 hours). Analysis was performed using Kaplan-Meier method.
- Part 2: Time to Progression (TTP) Per IMWG as Assessed by IRC [From start of study treatment to progression of disease or death, whichever occurred first (maximum duration of 17 months)]
IRC assessed TTP per 2016 IMWG criteria: Duration from start of study treatment until PD or death due to PD (per IRC), whichever occurred first. Progressive disease (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; Urinary M-protein (absolute increase must be >= 200 mg/24 hours). Analysis was performed using Kaplan-Meier method.
- Part 1: Time to Next Treatment (TTNT) [From start of study treatment to start of next anti-MM treatment or death due to disease progression, whichever occurs first (maximum duration of 13 months)]
TTNT was defined as the duration from start of study treatment to start of next anti-MM treatment or death due to disease progression, whichever occurred first. Analysis was performed using Kaplan-Meier method.
- Part 2: Time to Next Treatment (TTNT) [From start of study treatment to start of next anti-MM treatment or death due to disease progression, whichever occurs first (maximum duration of 17 months)]
TTNT was defined as the duration from start of study treatment to start of next anti-MM treatment or death due to disease progression, whichever occurred first. Analysis was performed using Kaplan-Meier method.
- Part 1: Overall Survival (OS) [From start of study treatment to death (maximum duration of 13 months)]
OS was defined as the duration (in months) from start of study treatment to death from any cause. Participants last known to be alive were censored at the date of discontinuation from the study, or database cut date, whichever was earlier. Analysis was performed using Kaplan-Meier method.
- Part 2: Overall Survival (OS) [From start of study treatment to death (maximum duration of 17 months)]
OS was defined as the duration (in months) from start of study treatment to death from any cause. Participants last known to be alive were censored at the date of discontinuation from the study, or database cut date, whichever was earlier. Analysis was performed using Kaplan-Meier method.
- Part 2: Change From Baseline in Health-related Quality of Life (HRQL) Score Based on Functional Assessment of Cancer Therapy - Multiple Myeloma (FACT-MM) Questionnaire [Baseline, Day 1 of Cycle 2 to Cycle 20 (up to a maximum of 17 months)]
FACT-MM combines the general version of the FACT (FACT-G) with a MM-specific sub-scale (14 items). The sub-scales for the FACT-G are Physical Well-Being (7 items), Social/Family Well-Being (7 items), Emotional Well-Being (6 items), and Functional Well-Being (7 items). The trial outcomes index (TOI); total of 41 items) is the primary measurement of interest, comprised of the Physical and Functional sub-scales plus the MM-specific sub-scale. Each item is rated on a 5-point Likert scale, ranging from 0 ("Not at all") to 4 ("Very much"), therefore the TOI has a score ranging from 0 to 120. Higher scores indicated improvement in well being.
- Number of Participants With Treatment-Emergent Adverse Events (TEAE) of Grade 3/4, Graded Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03 [Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)]
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. As per NCI-CTCAE version 4.03, Grade 1: asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. Treatment-emergent events are events between first dose of study drug and up to last dose of study treatment + 30 days (inclusive) that were absent before treatment or that worsened relative to pre-treatment state.
- Number of Participants With Treatment-Emergent Treatment-Related Adverse Events (TEAEs) of Grade 3/4, Graded Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03 [Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)]
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. As per NCI-CTCAE version 4.03, Grade 1: asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. A treatment related AE was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event had a causal relationship with the treatment or usage.
- Apparent Clearance (CL/F) of Selinexor in Plasma [Cycle 1: Day 1: Pre-dose, 1, 2 and 4 hours post-dose; Day 8 and 15: Pre-dose and 1 hour post-dose; Cycle 2: Day 1: Predose, 1, 2 and 4 hours post-dose]
CL/F of selinexor in plasma was reported.
- Volume of Distribution (V/F) of Selinexor in Plasma [Cycle 1: Day 1: Pre-dose, 1, 2 and 4 hours post-dose; Day 8 and 15: Pre-dose and 1 hour post-dose; Cycle 2: Day 1: Predose, 1, 2 and 4 hours post-dose]
Vz/F of selinexor in plasma was reported.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
Measurable MM based on modified IMWG guidelines. Defined by at least one of the following:
-
Serum M-protein ≥ 0.5 g/dL by serum electrophoresis (SPEP) or for IgA myeloma, by quantitative IgA
-
Urinary M-protein excretion ≥ 200 mg/24 hours
-
Free Light Chain (FLC) ≥ 100 mg/L, provided that the FLC ratio is abnormal
-
If serum protein electrophoresis is felt to be unreliable for routine M-protein measurement, then quantitative Ig levels by nephelometry or turbidimetry are acceptable
-
Must have previously received ≥ 3 anti-MM regimens including: an alkylating agent, lenalidomide, pomalidomide, bortezomib, carfilzomib, daratumumab, and a glucocorticoid. There is no upper limit on the number of prior therapies provided that all other inclusion/exclusion criteria are met.
-
MM refractory to previous treatment with one or more glucocorticoids, parenteral PI (i.e., bortezomib and/or carfilzomib), IMiD (i.e., lenalidomide and/or pomalidomide), and the anti-CD38 mAb, daratumumab. Refractory is defined as ≤ 25% response to therapy, or progression during therapy or progression within 60 days after completion of therapy.
Exclusion Criteria:
-
Active smoldering MM.
-
Active plasma cell leukemia.
-
Documented systemic amyloid light chain amyloidosis.
-
Active CNS MM.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Alabama | Birmingham | Alabama | United States | 35294 |
| 2 | Mayo Clinic (AZ) | Scottsdale | Arizona | United States | 85259 |
| 3 | City of Hope | Duarte | California | United States | 91010 |
| 4 | Jonnsson Comprehensive Cancer Center / University of Los Angeles | Los Angeles | California | United States | 90095 |
| 5 | Smilow Cancer Hospital | New Haven | Connecticut | United States | 06510 |
| 6 | University of Florida Health Cancer Center- Shands Cancer Center Hospital | Gainesville | Florida | United States | 32608 |
| 7 | Sylvester, University of Miami | Miami | Florida | United States | 33136 |
| 8 | H. Lee Moffitt Cancer Center Research Institute | Tampa | Florida | United States | 33612 |
| 9 | Emory University / Winship Cancer Institute | Atlanta | Georgia | United States | 30322 |
| 10 | Northside Hospital | Atlanta | Georgia | United States | 30342 |
| 11 | Kaiser Permanente- Hawaii | Honolulu | Hawaii | United States | 96819 |
| 12 | University of Chicago Medicine | Chicago | Illinois | United States | 60637 |
| 13 | Indiana University Simon Cancer Center | Indianapolis | Indiana | United States | 46202 |
| 14 | University of Iowa Hospitals & Clinics | Iowa City | Iowa | United States | 52242 |
| 15 | Norton Cancer Institute | Louisville | Kentucky | United States | 40202 |
| 16 | Johns Hopkins Medicine | Baltimore | Maryland | United States | 21287 |
| 17 | Tufts Medical Center | Boston | Massachusetts | United States | 02111 |
| 18 | Massachusetts General Hospital | Boston | Massachusetts | United States | 02114 |
| 19 | Dana Farber Cancer Institute | Boston | Massachusetts | United States | 02215 |
| 20 | University of Michigan | Ann Arbor | Michigan | United States | 48109 |
| 21 | Karmanos Cancer Institute / Wayne State University | Detroit | Michigan | United States | 48201 |
| 22 | Mayo Clinic Rochester | Rochester | Minnesota | United States | 55905 |
| 23 | Washington University St. Louis | Saint Louis | Missouri | United States | 63110 |
| 24 | Hackensack University Medical Center / John Therurer Cancer Center | Hackensack | New Jersey | United States | 07601 |
| 25 | Valley Hospital | Paramus | New Jersey | United States | 07652 |
| 26 | Roswell Park Cancer Institute | Buffalo | New York | United States | 14203 |
| 27 | NYU Perlmutter Cancer Center | New York | New York | United States | 10016 |
| 28 | Mt Sinai NYC | New York | New York | United States | 10029 |
| 29 | Columbia University | New York | New York | United States | 10032 |
| 30 | UNC-Chapel Hill | Chapel Hill | North Carolina | United States | 27514 |
| 31 | Gabrail Cancer Center | Canton | Ohio | United States | 44718 |
| 32 | Kaiser Permanente Northwest OR | Portland | Oregon | United States | |
| 33 | Abramson Cancer Center of the University of Pennsylvania | Philadelphia | Pennsylvania | United States | 19104 |
| 34 | Vanderbilt University Ingram Cancer Center | Nashville | Tennessee | United States | 37232 |
| 35 | Baylor Sammons Cancer Center | Dallas | Texas | United States | 75246 |
| 36 | Swedish Cancer Institute | Seattle | Washington | United States | 98109 |
| 37 | University Hospital Krems, Department of Internal Medicine II | Krems | Austria | ||
| 38 | Salzburg Regional Hospital Müllner | Salzburg | Austria | ||
| 39 | Medical University Vienna, Department of Internal Medicine I | Vienna | Austria | ||
| 40 | ZNA Stuivenberg | Antwerp | Belgium | ||
| 41 | General Hospital Saint-Jan | Brugge | Belgium | ||
| 42 | Jules Bordet Institute | Brussels | Belgium | 1000 | |
| 43 | UCL Saint-Luc | Brussels | Belgium | B-1200 | |
| 44 | University Hospital Ghent | Ghent | Belgium | ||
| 45 | University Hospital Leuven, Campus Gasthuisberg | Leuven | Belgium | ||
| 46 | UCL Mont-Godinne | Yvoir | Belgium | B-5530 | |
| 47 | Claude Huriez Hospital, Department of Blood Diseases | Lille | France | 59037 | |
| 48 | South Lyon Hospital Center, Department of Clinical Hematology | Lyon | France | 69002 | |
| 49 | Brabois Adults Hospital | Nancy | France | 54000 | |
| 50 | Nantes University Hospital Center | Nantes | France | 44093 | |
| 51 | Hopital Saint-Antoine, Service d´Hematologie Clinique et Therapie Cellulaire | Paris | France | 75012 | |
| 52 | La Pitie-Salpetriere University Hospital, Department of Clinical Hematology | Paris | France | 75013 | |
| 53 | Necker Children's Hospital | Paris | France | 75015 | |
| 54 | BAG Oncology Gemeinschaftspraxis | Dresden | Germany | 01307 | |
| 55 | University Hospital Freiburg, Department of Internal Medicine I | Freiburg | Germany | D-79106 | |
| 56 | Universitätsklinikum Heidelberg Medizinische Klinik V | Heidelberg | Germany | 69120 | |
| 57 | Universitätsklinikum des Saarlandes Klinik für Innere Medizin I | Homburg | Germany | 66421 | |
| 58 | Universitätsmedizin Mainz | Mainz | Germany | 55122 | |
| 59 | University hospital of Tuebingen, Internal Medicine II | Tübingen | Germany | ||
| 60 | Med. Klinik und Poliklinik II Universitätsklinikum | Würzburg | Germany | ||
| 61 | National & Kapodistrain University of Athens School of Medicine, Alexandra Hospital | Athens | Greece | 11528 |
Sponsors and Collaborators
- Karyopharm Therapeutics Inc
Investigators
- Study Director: Jatin Shah, Karyopharm Therapeutics Inc
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Karyopharm Therapeutics Inc
ClinicalTrials.gov Identifier:
NCT02336815
Other Study ID Numbers:
- KCP-330-012
First Posted:
Jan 13, 2015
Last Update Posted:
Nov 20, 2020
Last Verified:
Nov 1, 2020
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Keywords provided by Karyopharm Therapeutics Inc
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Part 1 of the study was conducted at 32 sites in the United States and Part 2 of the study was conducted at 59 sites in France, Germany, Belgium, Greece, Austria and United States. Enrollment in both parts was between from 26 May 2015 (first participant first visit)) and 26 July 2019 (last participant last visit). |
|---|---|
| Pre-assignment Detail | A total of 202 participants were enrolled in the study, out of which 79 participants were treated in Part 1 and 123 participants were treated in Part 2. |
| Arm/Group Title | Part 1 | Part 2 |
|---|---|---|
| Arm/Group Description | Participants with quad-exposed, double-class-refractory (i.e. previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, but not an anti-CD38 mab) and penta-exposed, triple-class-refractory multiple myeloma (MM) (i.e. previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, and daratumumab, and refractory to prior treatment with glucocorticoids, an immunomodulatory agent (IMiD), a proteasome inhibitor (PI), and the anti-CD38 mAb daratumumab) received, two dosing schedules (1) selinexor 80 milligrams (mg) plus low-dose dexamethasone 20 mg (Sd) twice-weekly on Days 1 and 3 for 3 weeks of each 4-week cycle (2) selinexor 80 mg plus low-dose dexamethasone 20 mg (Sd) twice-weekly continuously in 4-week cycles; until disease progression, death, or unacceptable toxicity (maximum duration of approximately 13 months). | Participants who previously had received more than 3 anti-MM regimens and had penta-exposed, triple class-refractory MM (i.e. previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, and daratumumab, and refractory to prior treatment with glucocorticoids, an IMiD, a PI, and the anti-CD38 mAb daratumumab) received, selinexor 80 mg post oral (PO) plus low-dose dexamethasone 20 mg Sd twice-weekly on Days 1 and 3 until disease progression, death, or unacceptable toxicity (maximum duration of approximately 17 months). |
| Period Title: Overall Study | ||
| STARTED | 79 | 123 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 79 | 123 |
Baseline Characteristics
| Arm/Group Title | Part 1 | Part 2 | Total |
|---|---|---|---|
| Arm/Group Description | Participants with quad-exposed, double-class-refractory (i.e. previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, but not an anti-CD38 mab) and penta-exposed, triple-class-refractory MM (i.e. previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, and daratumumab, and refractory to prior treatment with glucocorticoids, an IMiD, a PI, and the anti-CD38 mAb daratumumab) received, two dosing schedules (1) selinexor 80 mg plus low-dose dexamethasone 20 mg (Sd) twice-weekly on Days 1 and 3 for 3 weeks of each 4-week cycle (2) selinexor 80 mg plus low-dose dexamethasone 20 mg (Sd) twice-weekly continuously in 4-week cycles; until disease progression, death, or unacceptable toxicity (maximum duration of approximately 13 months). | Participants who previously had received more than 3 anti-MM regimens and had penta-exposed, triple class-refractory MM (i.e. previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, and daratumumab, and refractory to prior treatment with glucocorticoids, an IMiD, a PI, and the anti-CD38 mAb daratumumab) received, selinexor 80 mg PO plus low-dose dexamethasone 20 mg Sd twice-weekly on Days 1 and 3 until disease progression, death, or unacceptable toxicity (maximum duration of approximately 17 months). | Total of all reporting groups |
| Overall Participants | 79 | 123 | 202 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
62.9
(8.79)
|
64.5
(9.41)
|
63.9
(9.18)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
42
53.2%
|
52
42.3%
|
94
46.5%
|
| Male |
37
46.8%
|
71
57.7%
|
108
53.5%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
2
2.5%
|
9
7.3%
|
11
5.4%
|
| Not Hispanic or Latino |
75
94.9%
|
97
78.9%
|
172
85.1%
|
| Unknown or Not Reported |
2
2.5%
|
17
13.8%
|
19
9.4%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
2
1.6%
|
2
1%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
1
0.8%
|
1
0.5%
|
| Black or African American |
14
17.7%
|
21
17.1%
|
35
17.3%
|
| White |
62
78.5%
|
86
69.9%
|
148
73.3%
|
| More than one race |
2
2.5%
|
8
6.5%
|
10
5%
|
| Unknown or Not Reported |
1
1.3%
|
5
4.1%
|
6
3%
|
Outcome Measures
| Title | Part 2: Percentage of Participants With Overall Response Rate (ORR) Per International MyelomaWorking Group (IMWG) as Assessed by an Independent Review Committee (IRC) |
|---|---|
| Description | IRC assessed ORR per 2016 IMWG criteria: Percentage of participants who experienced Partial response (PR): greater than or equal to (>=) 50 percent (%) reduction of serum M-Protein and reduction in 24-hour urinary M-protein by >= 90% or to lesser than (<) 200 mg per 24 hours; Very good partial response (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; Complete response (CR): Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and lesser than or equal to (<=) 5% plasma cells in bone marrow; or stringent complete response (sCR): CR as defined+Normal free light chain (FLC) ratio+Absence of clonal cells in bone marrow biopsy by immunohistochemistry). |
| Time Frame | Baseline until disease progression/discontinuation from the study, or death, whichever occurred first (maximum duration of 17 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Modified intent-to-treat (mITT) population consisted of Part 2 participants with penta-refractory MM who met all eligibility criteria and received at least one dose of study treatment. Data was not planned to be collected and analyzed for Part 1. |
| Arm/Group Title | Part 2 |
|---|---|
| Arm/Group Description | Participants who previously had received more than 3 anti-MM regimens and had penta-exposed, triple class-refractory MM (i.e. previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, and daratumumab, and refractory to prior treatment with glucocorticoids, an IMiD, a PI, and the anti-CD38 mAb daratumumab) received, selinexor 80 mg PO plus low-dose dexamethasone 20 mg Sd twice-weekly on Days 1 and 3 until disease progression, death, or unacceptable toxicity (maximum duration of approximately 17 months). |
| Measure Participants | 122 |
| Number (95% Confidence Interval) [Percentage of Participants] |
26.2
33.2%
|
| Title | Part 1: Duration of Response (DoR) Per IMWG as Assessed by IRC |
|---|---|
| Description | IRC assessed DoR per 2016 IMWG criteria: time (in months) from the first documentation of objective response (confirmed CR or PR) to the date of first documentation of progressive disease (PD) or death due to any cause. Partial response (PR): >= 50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by >= 90% or to < 200 mg per 24 hours; Complete response (CR): Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and <= 5% plasma cells in bone marrow; Progressive disease (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 gram per deciliter (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. |
| Time Frame | First response subsequently confirmed to disease progression/discontinuation from the study, or death, whichever occurred first (maximum duration of 13 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population consisted of all participants, who had received at least 1 dose of study treatment (partial or complete) and had any post-baseline safety information. Here, "Overall number of participants analyzed" signifies those participants who were evaluable for this outcome measure. |
| Arm/Group Title | Part 1 |
|---|---|
| Arm/Group Description | Participants with quad-exposed, double-class-refractory (i.e. previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, but not an anti-CD38 mab) and penta-exposed, triple-class-refractory MM (i.e. previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, and daratumumab, and refractory to prior treatment with glucocorticoids, an IMiD, a PI, and the anti-CD38 mAb daratumumab) received, two dosing schedules (1) selinexor 80 mg plus low-dose dexamethasone 20 mg (Sd) twice-weekly on Days 1 and 3 for 3 weeks of each 4-week cycle (2) selinexor 80 mg plus low-dose dexamethasone 20 mg (Sd) twice-weekly continuously in 4-week cycles; until disease progression, death, or unacceptable toxicity (maximum duration of approximately 13 months). |
| Measure Participants | 16 |
| Median (95% Confidence Interval) [Months] |
6.2
|
| Title | Part 2: Duration of Response (DoR) Per IMWG as Assessed by an IRC |
|---|---|
| Description | IRC assessed DoR per 2016 IMWG criteria: time (in months) from the first documentation of objective response (confirmed CR or PR) to the date of first documentation of progressive disease (PD) or death due to any cause. Partial response (PR): >= 50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by >= 90% or to < 200 mg per 24 hours; Complete response (CR): Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and <= 5% plasma cells in bone marrow; Progressive disease (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. |
| Time Frame | First response subsequently confirmed to disease progression/discontinuation from the study, or death, whichever occurred first (maximum duration of 17 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT population consisted of Part 2 participants with penta-refractory MM who met all eligibility criteria and received at least one dose of study treatment. Here, "Overall number of participants analyzed" signifies those participants who were evaluable for this outcome measure. |
| Arm/Group Title | Part 2 |
|---|---|
| Arm/Group Description | Participants who previously had received more than 3 anti-MM regimens and had penta-exposed, triple class-refractory MM (i.e. previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, and daratumumab, and refractory to prior treatment with glucocorticoids, an IMiD, a PI, and the anti-CD38 mAb daratumumab) received, selinexor 80 mg PO plus low-dose dexamethasone 20 mg Sd twice-weekly on Days 1 and 3 until disease progression, death, or unacceptable toxicity (maximum duration of approximately 17 months). |
| Measure Participants | 32 |
| Median (95% Confidence Interval) [Months] |
4.4
|
| Title | Part 1: Percentage of Participants With Clinical Benefit Rate (CBR) ) Per IMWG as Assessed by IRC |
|---|---|
| Description | IRC assessed CBR per 2016 IMWG criteria: Percentage of participants with a confirmed minimal response (MR) or better (PR, VGPR, CR or sCR) before confirmed disease progression or initiating new MM treatment. Minimal response (MR): >= 25% but < 49% reduction of serum M-protein and reduction in 24-hour urinary M-protein by 50-89%. Partial response (PR): >= 50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by >= 90% or to < 200 mg per 24 hours; Very good partial response (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; Complete response (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+Normal free light chain (FLC) ratio+Absence of clonal cells by immunohistochemistry). |
| Time Frame | Baseline up to a maximum of 13 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population consisted of all participants, who had received at least 1 dose of study treatment (partial or complete) and had any post-baseline safety information. |
| Arm/Group Title | Part 1 |
|---|---|
| Arm/Group Description | Participants with quad-exposed, double-class-refractory (i.e. previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, but not an anti-CD38 mab) and penta-exposed, triple-class-refractory MM (i.e. previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, and daratumumab, and refractory to prior treatment with glucocorticoids, an IMiD, a PI, and the anti-CD38 mAb daratumumab) received, two dosing schedules (1) selinexor 80 mg plus low-dose dexamethasone 20 mg (Sd) twice-weekly on Days 1 and 3 for 3 weeks of each 4-week cycle (2) selinexor 80 mg plus low-dose dexamethasone 20 mg (Sd) twice-weekly continuously in 4-week cycles; until disease progression, death, or unacceptable toxicity (maximum duration of approximately 13 months). |
| Measure Participants | 79 |
| Number (95% Confidence Interval) [Percentage of Participants] |
31.6
40%
|
| Title | Part 2: Percentage of Participants With Clinical Benefit Rate (CBR) Per IMWG as Assessed by IRC |
|---|---|
| Description | IRC assessed CBR per 2016 IMWG criteria: Percentage of participants with a confirmed minimal response (MR) or better (PR, VGPR, CR or sCR) before confirmed disease progression or initiating new MM treatment. Minimal response (MR): >= 25% but < 49% reduction of serum M-protein and reduction in 24-hour urinary M-protein by 50-89%. Partial response (PR): >= 50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by >= 90% or to < 200 mg per 24 hours; Very good partial response (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; Complete response (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+Normal free light chain (FLC) ratio+Absence of clonal cells by immunohistochemistry). |
| Time Frame | Baseline up to a maximum of 17 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT population consisted of Part 2 participants with penta-refractory MM who met all eligibility criteria and received at least one dose of study treatment. |
| Arm/Group Title | Part 2 |
|---|---|
| Arm/Group Description | Participants who previously had received more than 3 anti-MM regimens and had penta-exposed, triple class-refractory MM (i.e. previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, and daratumumab, and refractory to prior treatment with glucocorticoids, an IMiD, a PI, and the anti-CD38 mAb daratumumab) received, selinexor 80 mg PO plus low-dose dexamethasone 20 mg Sd twice-weekly on Days 1 and 3 until disease progression, death, or unacceptable toxicity (maximum duration of approximately 17 months). |
| Measure Participants | 122 |
| Number (95% Confidence Interval) [Percentage of Participants] |
39.3
49.7%
|
| Title | Part 1: Duration of Clinical Benefit Per IMWG as Assessed by IRC |
|---|---|
| Description | IRC assessed duration of clinical benefit per 2016 IMWG criteria: Duration from first response (at least MR) to time of IRC-determined PD or death due to disease progression, whichever occurs first. Minimal response (MR): >= 25% but < 49% reduction of serum M-protein and reduction in 24-hour urinary M-protein by 50-89%. Progressive disease (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; Urinary M-protein (absolute increase must be >= 200 mg per 24 hours). Analysis was performed using Kaplan-Meier method. |
| Time Frame | First response subsequently confirmed to disease progression, or death, whichever occurred first (maximum duration of 13 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population consisted of all participants, who had received at least 1 dose of study treatment (partial or complete) and had any post-baseline safety information. Here, "Overall number of participants analyzed" signifies those participants who were evaluable for this outcome measure. |
| Arm/Group Title | Part 1 |
|---|---|
| Arm/Group Description | Participants with quad-exposed, double-class-refractory (i.e. previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, but not an anti-CD38 mab) and penta-exposed, triple-class-refractory MM (i.e. previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, and daratumumab, and refractory to prior treatment with glucocorticoids, an IMiD, a PI, and the anti-CD38 mAb daratumumab) received, two dosing schedules (1) selinexor 80 mg plus low-dose dexamethasone 20 mg (Sd) twice-weekly on Days 1 and 3 for 3 weeks of each 4-week cycle (2) selinexor 80 mg plus low-dose dexamethasone 20 mg (Sd) twice-weekly continuously in 4-week cycles; until disease progression, death, or unacceptable toxicity (maximum duration of approximately 13 months). |
| Measure Participants | 25 |
| Median (95% Confidence Interval) [Months] |
5.6
|
| Title | Part 2: Duration of Clinical Benefit Per IMWG as Assessed by IRC |
|---|---|
| Description | IRC assessed duration of clinical benefit per 2016 IMWG criteria: Duration from first response (at least MR) to time of IRC-determined PD or death due to disease progression, whichever occurs first. Minimal response (MR): >= 25% but < 49% reduction of serum M-protein and reduction in 24-hour urinary M-protein by 50-89%. Progressive disease (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; Urinary M-protein (absolute increase must be >= 200 mg per 24 hours). Analysis was performed using Kaplan-Meier method. |
| Time Frame | First response subsequently confirmed to disease progression, or death, whichever occurred first (maximum duration of 17 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| miTT population consisted of Part 2 participants with penta-refractory MM who met all eligibility criteria and received at least one dose of study treatment. Here, "Overall number of participants analyzed" signifies those participants who were evaluable for this outcome measure. |
| Arm/Group Title | Part 2 |
|---|---|
| Arm/Group Description | Participants who previously had received more than 3 anti-MM regimens and had penta-exposed, triple class-refractory MM (i.e. previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, and daratumumab, and refractory to prior treatment with glucocorticoids, an IMiD, a PI, and the anti-CD38 mAb daratumumab) received, selinexor 80 mg PO plus low-dose dexamethasone 20 mg Sd twice-weekly on Days 1 and 3 until disease progression, death, or unacceptable toxicity (maximum duration of approximately 17 months). |
| Measure Participants | 48 |
| Median (95% Confidence Interval) [Months] |
3.8
|
| Title | Part 2: Disease Control Rate (DCR) |
|---|---|
| Description | DCR was defined as the percentage of participants who achieved stable disease (SD) or better (MR, PR, VGPR, CR, sCR) for a minimum of 12 weeks. Stable disease (SD): Not recommended for use as an indicator of response; stability of disease was best described by providing the time to progression (TTP) estimates. MR: >= 25% but < 49% reduction of serum M-protein and reduction in 24-hour urinary M-protein by 50-89%. 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: CR as defined+Normal FLC ratio+Absence of clonal cells by immunohistochemistry). |
| Time Frame | Every 12 weeks until progressive disease or death due to any cause, up to 17 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT population consisted of Part 2 participants with penta-refractory MM who met all eligibility criteria and received at least one dose of study treatment. Data was not planned to be collected and analyzed for Part 1. |
| Arm/Group Title | Part 2 |
|---|---|
| Arm/Group Description | Participants who previously had received more than 3 anti-MM regimens and had penta-exposed, triple class-refractory MM (i.e. previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, and daratumumab, and refractory to prior treatment with glucocorticoids, an IMiD, a PI, and the anti-CD38 mAb daratumumab) received, selinexor 80 mg PO plus low-dose dexamethasone 20 mg Sd twice-weekly on Days 1 and 3 until disease progression, death, or unacceptable toxicity (maximum duration of approximately 17 months). |
| Measure Participants | 122 |
| Number (95% Confidence Interval) [Percentage of Participants] |
44.3
56.1%
|
| Title | Part 1: Progression Free Survival (PFS) Per IMWG as Assessed by IRC |
|---|---|
| Description | IRC assessed PFS per 2016 IMWG criteria: Duration from start of study treatment until IRC-determined progressive disease (PD) or death from any cause, whichever occurred first. Progressive disease (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; Urinary M-protein (absolute increase must be >= 200 mg/24 hours). Analysis was performed using Kaplan-Meier method. |
| Time Frame | From start of study treatment to progression of disease or discontinuation from the study or death, whichever occurred first (maximum duration of 13 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population consisted of all participants, who had received at least 1 dose of study treatment (partial or complete) and had any post-baseline safety information. |
| Arm/Group Title | Part 1 |
|---|---|
| Arm/Group Description | Participants with quad-exposed, double-class-refractory (i.e. previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, but not an anti-CD38 mab) and penta-exposed, triple-class-refractory MM (i.e. previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, and daratumumab, and refractory to prior treatment with glucocorticoids, an IMiD, a PI, and the anti-CD38 mAb daratumumab) received, two dosing schedules (1) selinexor 80 mg plus low-dose dexamethasone 20 mg (Sd) twice-weekly on Days 1 and 3 for 3 weeks of each 4-week cycle (2) selinexor 80 mg plus low-dose dexamethasone 20 mg (Sd) twice-weekly continuously in 4-week cycles; until disease progression, death, or unacceptable toxicity (maximum duration of approximately 13 months). |
| Measure Participants | 79 |
| Median (95% Confidence Interval) [Months] |
4.7
|
| Title | Part 2: Progression Free Survival (PFS) Per IMWG as Assessed by IRC |
|---|---|
| Description | IRC assessed PFS per 2016 IMWG criteria: Duration from start of study treatment until IRC-determined progressive disease (PD) or death from any cause, whichever occurred first. Progressive disease (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; Urinary M-protein (absolute increase must be >= 200 mg/24 hours). Analysis was performed using Kaplan-Meier method. |
| Time Frame | From start of study treatment to progression of disease or discontinuation from the study or death, whichever occurred first (maximum duration of 17 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT population consisted of Part 2 participants with penta-refractory MM who met all eligibility criteria and received at least one dose of study treatment. |
| Arm/Group Title | Part 2 |
|---|---|
| Arm/Group Description | Participants who previously had received more than 3 anti-MM regimens and had penta-exposed, triple class-refractory MM (i.e. previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, and daratumumab, and refractory to prior treatment with glucocorticoids, an IMiD, a PI, and the anti-CD38 mAb daratumumab) received, selinexor 80 mg PO plus low-dose dexamethasone 20 mg Sd twice-weekly on Days 1 and 3 until disease progression, death, or unacceptable toxicity (maximum duration of approximately 17 months). |
| Measure Participants | 122 |
| Median (95% Confidence Interval) [Months] |
3.7
|
| Title | Part 1: Time to Progression (TTP) Per IMWG as Assessed by IRC |
|---|---|
| Description | IRC assessed TTP per 2016 IMWG criteria: Duration from start of study treatment until PD or death due to PD (per IRC), whichever occurred first. Progressive disease (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; Urinary M-protein (absolute increase must be >= 200 mg/24 hours). Analysis was performed using Kaplan-Meier method. |
| Time Frame | From start of study treatment to progression of disease or death, whichever occurred first (maximum duration of 13 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population consisted of all participants, who had received at least 1 dose of study treatment (partial or complete) and had any post-baseline safety information. |
| Arm/Group Title | Part 1 |
|---|---|
| Arm/Group Description | Participants with quad-exposed, double-class-refractory (i.e. previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, but not an anti-CD38 mab) and penta-exposed, triple-class-refractory MM (i.e. previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, and daratumumab, and refractory to prior treatment with glucocorticoids, an IMiD, a PI, and the anti-CD38 mAb daratumumab) received, two dosing schedules (1) selinexor 80 mg plus low-dose dexamethasone 20 mg (Sd) twice-weekly on Days 1 and 3 for 3 weeks of each 4-week cycle (2) selinexor 80 mg plus low-dose dexamethasone 20 mg (Sd) twice-weekly continuously in 4-week cycles; until disease progression, death, or unacceptable toxicity (maximum duration of approximately 13 months). |
| Measure Participants | 79 |
| Median (95% Confidence Interval) [Months] |
5.5
|
| Title | Part 2: Time to Progression (TTP) Per IMWG as Assessed by IRC |
|---|---|
| Description | IRC assessed TTP per 2016 IMWG criteria: Duration from start of study treatment until PD or death due to PD (per IRC), whichever occurred first. Progressive disease (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; Urinary M-protein (absolute increase must be >= 200 mg/24 hours). Analysis was performed using Kaplan-Meier method. |
| Time Frame | From start of study treatment to progression of disease or death, whichever occurred first (maximum duration of 17 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT population consisted of Part 2 participants with penta-refractory MM who met all eligibility criteria and received at least one dose of study treatment. |
| Arm/Group Title | Part 2 |
|---|---|
| Arm/Group Description | Participants who previously had received more than 3 anti-MM regimens and had penta-exposed, triple class-refractory MM (i.e. previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, and daratumumab, and refractory to prior treatment with glucocorticoids, an IMiD, a PI, and the anti-CD38 mAb daratumumab) received, selinexor 80 mg PO plus low-dose dexamethasone 20 mg Sd twice-weekly on Days 1 and 3 until disease progression, death, or unacceptable toxicity (maximum duration of approximately 17 months). |
| Measure Participants | 122 |
| Median (95% Confidence Interval) [Months] |
4.1
|
| Title | Part 1: Time to Next Treatment (TTNT) |
|---|---|
| Description | TTNT was defined as the duration from start of study treatment to start of next anti-MM treatment or death due to disease progression, whichever occurred first. Analysis was performed using Kaplan-Meier method. |
| Time Frame | From start of study treatment to start of next anti-MM treatment or death due to disease progression, whichever occurs first (maximum duration of 13 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population consisted of all participants, who had received at least 1 dose of study treatment (partial or complete) and had any post-baseline safety information. |
| Arm/Group Title | Part 1 |
|---|---|
| Arm/Group Description | Participants with quad-exposed, double-class-refractory (i.e. previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, but not an anti-CD38 mab) and penta-exposed, triple-class-refractory MM (i.e. previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, and daratumumab, and refractory to prior treatment with glucocorticoids, an IMiD, a PI, and the anti-CD38 mAb daratumumab) received, two dosing schedules (1) selinexor 80 mg plus low-dose dexamethasone 20 mg (Sd) twice-weekly on Days 1 and 3 for 3 weeks of each 4-week cycle (2) selinexor 80 mg plus low-dose dexamethasone 20 mg (Sd) twice-weekly continuously in 4-week cycles; until disease progression, death, or unacceptable toxicity (maximum duration of approximately 13 months). |
| Measure Participants | 79 |
| Median (95% Confidence Interval) [Months] |
2.6
|
| Title | Part 2: Time to Next Treatment (TTNT) |
|---|---|
| Description | TTNT was defined as the duration from start of study treatment to start of next anti-MM treatment or death due to disease progression, whichever occurred first. Analysis was performed using Kaplan-Meier method. |
| Time Frame | From start of study treatment to start of next anti-MM treatment or death due to disease progression, whichever occurs first (maximum duration of 17 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT population consisted of Part 2 participants with penta-refractory MM who met all eligibility criteria and received at least one dose of study treatment. |
| Arm/Group Title | Part 2 |
|---|---|
| Arm/Group Description | Participants who previously had received more than 3 anti-MM regimens and had penta-exposed, triple class-refractory MM (i.e. previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, and daratumumab, and refractory to prior treatment with glucocorticoids, an IMiD, a PI, and the anti-CD38 mAb daratumumab) received, selinexor 80 mg PO plus low-dose dexamethasone 20 mg Sd twice-weekly on Days 1 and 3 until disease progression, death, or unacceptable toxicity (maximum duration of approximately 17 months). |
| Measure Participants | 122 |
| Median (95% Confidence Interval) [Months] |
3.2
|
| Title | Part 1: Overall Survival (OS) |
|---|---|
| Description | OS was defined as the duration (in months) from start of study treatment to death from any cause. Participants last known to be alive were censored at the date of discontinuation from the study, or database cut date, whichever was earlier. Analysis was performed using Kaplan-Meier method. |
| Time Frame | From start of study treatment to death (maximum duration of 13 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population consisted of all participants, who had received at least 1 dose of study treatment (partial or complete) and had any post-baseline safety information. |
| Arm/Group Title | Part 1 |
|---|---|
| Arm/Group Description | Participants with quad-exposed, double-class-refractory (i.e. previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, but not an anti-CD38 mab) and penta-exposed, triple-class-refractory MM (i.e. previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, and daratumumab, and refractory to prior treatment with glucocorticoids, an IMiD, a PI, and the anti-CD38 mAb daratumumab) received, two dosing schedules (1) selinexor 80 mg plus low-dose dexamethasone 20 mg (Sd) twice-weekly on Days 1 and 3 for 3 weeks of each 4-week cycle (2) selinexor 80 mg plus low-dose dexamethasone 20 mg (Sd) twice-weekly continuously in 4-week cycles; until disease progression, death, or unacceptable toxicity (maximum duration of approximately 13 months). |
| Measure Participants | 79 |
| Median (95% Confidence Interval) [Months] |
7.3
|
| Title | Part 2: Overall Survival (OS) |
|---|---|
| Description | OS was defined as the duration (in months) from start of study treatment to death from any cause. Participants last known to be alive were censored at the date of discontinuation from the study, or database cut date, whichever was earlier. Analysis was performed using Kaplan-Meier method. |
| Time Frame | From start of study treatment to death (maximum duration of 17 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT population consisted of Part 2 participants with penta-refractory MM who met all eligibility criteria and received at least one dose of study treatment. |
| Arm/Group Title | Part 2 |
|---|---|
| Arm/Group Description | Participants who previously had received more than 3 anti-MM regimens and had penta-exposed, triple class-refractory MM (i.e. previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, and daratumumab, and refractory to prior treatment with glucocorticoids, an IMiD, a PI, and the anti-CD38 mAb daratumumab) received, selinexor 80 mg PO plus low-dose dexamethasone 20 mg Sd twice-weekly on Days 1 and 3 until disease progression, death, or unacceptable toxicity (maximum duration of approximately 17 months). |
| Measure Participants | 122 |
| Median (95% Confidence Interval) [Months] |
8.4
|
| Title | Part 2: Change From Baseline in Health-related Quality of Life (HRQL) Score Based on Functional Assessment of Cancer Therapy - Multiple Myeloma (FACT-MM) Questionnaire |
|---|---|
| Description | FACT-MM combines the general version of the FACT (FACT-G) with a MM-specific sub-scale (14 items). The sub-scales for the FACT-G are Physical Well-Being (7 items), Social/Family Well-Being (7 items), Emotional Well-Being (6 items), and Functional Well-Being (7 items). The trial outcomes index (TOI); total of 41 items) is the primary measurement of interest, comprised of the Physical and Functional sub-scales plus the MM-specific sub-scale. Each item is rated on a 5-point Likert scale, ranging from 0 ("Not at all") to 4 ("Very much"), therefore the TOI has a score ranging from 0 to 120. Higher scores indicated improvement in well being. |
| Time Frame | Baseline, Day 1 of Cycle 2 to Cycle 20 (up to a maximum of 17 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT population set. Here, "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure at given time points. Data was not planned to be collected and analyzed for Part 1. |
| Arm/Group Title | Part 2 |
|---|---|
| Arm/Group Description | Participants who previously had received more than 3 anti-MM regimens and had penta-exposed, triple class-refractory MM (i.e. previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, and daratumumab, and refractory to prior treatment with glucocorticoids, an IMiD, a PI, and the anti-CD38 mAb daratumumab) received, selinexor 80 mg PO plus low-dose dexamethasone 20 mg Sd twice-weekly on Days 1 and 3 until disease progression, death, or unacceptable toxicity (maximum duration of approximately 17 months). |
| Measure Participants | 107 |
| Trial Outcomes Index Score: Baseline |
67.5
(19.20)
|
| Trial Outcomes Index Score: Change at C2D1 |
-6.1
(18.43)
|
| Trial Outcomes Index Score: Change at C3D1 |
-8.5
(15.50)
|
| Trial Outcomes Index Score: Change at C4D1 |
-9.1
(16.79)
|
| Trial Outcomes Index Score: Change at C5D1 |
-6.9
(12.06)
|
| Trial Outcomes Index Score: Change at C6D1 |
-8.3
(15.07)
|
| Trial Outcomes Index Score: Change at C7D1 |
-7.5
(19.26)
|
| Trial Outcomes Index Score: Change at C8D1 |
-15.4
(24.59)
|
| Trial Outcomes Index Score: Change at C9D1 |
-4.7
(14.84)
|
| Trial Outcomes Index Score: Change at C10D1 |
-4.0
(5.29)
|
| Trial Outcomes Index Score: Change at C11D1 |
3.0
(NA)
|
| Trial Outcomes Index Score: Change at C12D1 |
3.0
(NA)
|
| Trial Outcomes Index Score: Change at C13D1 |
-23.0
(NA)
|
| Trial Outcomes Index Score: Change at C14D1 |
14.0
(NA)
|
| Trial Outcomes Index Score: Change at C15D1 |
1.0
(NA)
|
| Trial Outcomes Index Score: Change at C16D1 |
4.0
(NA)
|
| Title | Number of Participants With Treatment-Emergent Adverse Events (TEAE) of Grade 3/4, Graded Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03 |
|---|---|
| Description | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. As per NCI-CTCAE version 4.03, Grade 1: asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. Treatment-emergent events are events between first dose of study drug and up to last dose of study treatment + 30 days (inclusive) that were absent before treatment or that worsened relative to pre-treatment state. |
| Time Frame | Baseline to 30 days after last dose of study treatment (maximum duration of 18 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population consisted of all participants, who had received at least 1 dose of study treatment (partial or complete) and had any post-baseline safety information. |
| Arm/Group Title | Part 1 | Part 2 |
|---|---|---|
| Arm/Group Description | Participants with quad-exposed, double-class-refractory (i.e. previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, but not an anti-CD38 mab) and penta-exposed, triple-class-refractory MM (i.e. previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, and daratumumab, and refractory to prior treatment with glucocorticoids, an IMiD, a PI, and the anti-CD38 mAb daratumumab) received, two dosing schedules (1) selinexor 80 mg plus low-dose dexamethasone 20 mg (Sd) twice-weekly on Days 1 and 3 for 3 weeks of each 4-week cycle (2) selinexor 80 mg plus low-dose dexamethasone 20 mg (Sd) twice-weekly continuously in 4-week cycles; until disease progression, death, or unacceptable toxicity (maximum duration of approximately 13 months). | Participants who previously had received more than 3 anti-MM regimens and had penta-exposed, triple class-refractory MM (i.e. previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, and daratumumab, and refractory to prior treatment with glucocorticoids, an IMiD, a PI, and the anti-CD38 mAb daratumumab) received, selinexor 80 mg PO plus low-dose dexamethasone 20 mg Sd twice-weekly on Days 1 and 3 until disease progression, death, or unacceptable toxicity (maximum duration of approximately 17 months). |
| Measure Participants | 79 | 123 |
| Count of Participants [Participants] |
75
94.9%
|
115
93.5%
|
| Title | Number of Participants With Treatment-Emergent Treatment-Related Adverse Events (TEAEs) of Grade 3/4, Graded Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03 |
|---|---|
| Description | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. As per NCI-CTCAE version 4.03, Grade 1: asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. A treatment related AE was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event had a causal relationship with the treatment or usage. |
| Time Frame | Baseline to 30 days after last dose of study treatment (maximum duration of 18 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population consisted of all participants, who had received at least 1 dose of study treatment (partial or complete) and had any post-baseline safety information. |
| Arm/Group Title | Part 1 | Part 2 |
|---|---|---|
| Arm/Group Description | Participants with quad-exposed, double-class-refractory (i.e. previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, but not an anti-CD38 mab) and penta-exposed, triple-class-refractory MM (i.e. previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, and daratumumab, and refractory to prior treatment with glucocorticoids, an IMiD, a PI, and the anti-CD38 mAb daratumumab) received, two dosing schedules (1) selinexor 80 mg plus low-dose dexamethasone 20 mg (Sd) twice-weekly on Days 1 and 3 for 3 weeks of each 4-week cycle (2) selinexor 80 mg plus low-dose dexamethasone 20 mg (Sd) twice-weekly continuously in 4-week cycles; until disease progression, death, or unacceptable toxicity (maximum duration of approximately 13 months | Participants who previously had received more than 3 anti-MM regimens and had penta-exposed, triple class-refractory MM (i.e. previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, and daratumumab, and refractory to prior treatment with glucocorticoids, an IMiD, a PI, and the anti-CD38 mAb daratumumab) received, selinexor 80 mg PO plus low-dose dexamethasone 20 mg Sd twice-weekly on Days 1 and 3 until disease progression, death, or unacceptable toxicity (maximum duration of approximately 17 months). |
| Measure Participants | 79 | 123 |
| Count of Participants [Participants] |
69
87.3%
|
110
89.4%
|
| Title | Apparent Clearance (CL/F) of Selinexor in Plasma |
|---|---|
| Description | CL/F of selinexor in plasma was reported. |
| Time Frame | Cycle 1: Day 1: Pre-dose, 1, 2 and 4 hours post-dose; Day 8 and 15: Pre-dose and 1 hour post-dose; Cycle 2: Day 1: Predose, 1, 2 and 4 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic (PK) set included all participants in Part 1 who received at least 1 dose of investigational product in this study. Data was not planned to be collected and analyzed for Part 2. |
| Arm/Group Title | Part 1 |
|---|---|
| Arm/Group Description | Participants with quad-exposed, double-class-refractory (i.e. previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, but not an anti-CD38 mab) and penta-exposed, triple-class-refractory MM (i.e. previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, and daratumumab, and refractory to prior treatment with glucocorticoids, an IMiD, a PI, and the anti-CD38 mAb daratumumab) received, two dosing schedules (1) selinexor 80 mg plus low-dose dexamethasone 20 mg (Sd) twice-weekly on Days 1 and 3 for 3 weeks of each 4-week cycle (2) selinexor 80 mg plus low-dose dexamethasone 20 mg (Sd) twice-weekly continuously in 4-week cycles; until disease progression, death, or unacceptable toxicity (maximum duration of approximately 13 months). |
| Measure Participants | 79 |
| Mean (Standard Deviation) [Liters/Hour] |
16.6
(2.8)
|
| Title | Volume of Distribution (V/F) of Selinexor in Plasma |
|---|---|
| Description | Vz/F of selinexor in plasma was reported. |
| Time Frame | Cycle 1: Day 1: Pre-dose, 1, 2 and 4 hours post-dose; Day 8 and 15: Pre-dose and 1 hour post-dose; Cycle 2: Day 1: Predose, 1, 2 and 4 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic (PK) set included all participants in Part 1 who received at least 1 dose of investigational product in this study. Data was not planned to be collected and analyzed for Part 2. |
| Arm/Group Title | Part 1 |
|---|---|
| Arm/Group Description | Participants with quad-exposed, double-class-refractory (i.e. previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, but not an anti-CD38 mab) and penta-exposed, triple-class-refractory MM (i.e. previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, and daratumumab, and refractory to prior treatment with glucocorticoids, an IMiD, a PI, and the anti-CD38 mAb daratumumab) received, two dosing schedules (1) selinexor 80 mg plus low-dose dexamethasone 20 mg (Sd) twice-weekly on Days 1 and 3 for 3 weeks of each 4-week cycle (2) selinexor 80 mg plus low-dose dexamethasone 20 mg (Sd) twice-weekly continuously in 4-week cycles; until disease progression, death, or unacceptable toxicity (maximum duration of approximately 13 months). |
| Measure Participants | 79 |
| Mean (Standard Deviation) [Liter] |
145.6
(28.2)
|
Adverse Events
| Time Frame | Baseline to 30 days after last dose of study treatment (maximum duration of 18 months) | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Part 1 | Part 2 | ||
| Arm/Group Description | Participants with quad-exposed, double-class-refractory (i.e. previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, but not an anti-CD38 mab) and penta-exposed, triple-class-refractory MM (i.e. previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, and daratumumab, and refractory to prior treatment with glucocorticoids, an IMiD, a PI, and the anti-CD38 mAb daratumumab) received, two dosing schedules (1) Selinexor 80 mg plus low-dose dexamethasone 20 mg (Sd) twice-weekly on Days 1 and 3 for 3 weeks of each 4-week cycle (2) Selinexor 80 mg plus low-dose dexamethasone 20 mg (Sd) twice-weekly continuously in 4-week cycles; until disease progression, death, or unacceptable toxicity (maximum duration of approximately 13 months). | Participants who previously had received more than 3 anti-MM regimens and had penta-exposed, triple class-refractory MM (i.e. previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, and daratumumab, and refractory to prior treatment with glucocorticoids, an IMiD, a PI, and the anti-CD38 mAb daratumumab) received, Selinexor 80 mg post oral (PO) plus low-dose dexamethasone 20 mg Sd twice-weekly on Days 1 and 3 until disease progression, death, or unacceptable toxicity (maximum duration of approximately 17 months). | ||
All Cause Mortality |
||||
| Part 1 | Part 2 | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 20/79 (25.3%) | 28/123 (22.8%) | ||
Serious Adverse Events |
||||
| Part 1 | Part 2 | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 45/79 (57%) | 78/123 (63.4%) | ||
| Blood and lymphatic system disorders | ||||
| Thrombocytopenia | 5/79 (6.3%) | 5 | 3/123 (2.4%) | 3 |
| Anaemia | 2/79 (2.5%) | 2 | 4/123 (3.3%) | 4 |
| Febrile neutropenia | 3/79 (3.8%) | 3 | 0/123 (0%) | 0 |
| Leukopenia | 1/79 (1.3%) | 1 | 0/123 (0%) | 0 |
| Lymphopenia | 1/79 (1.3%) | 1 | 0/123 (0%) | 0 |
| Neutropenia | 0/79 (0%) | 0 | 1/123 (0.8%) | 1 |
| Cardiac disorders | ||||
| Cardio-respiratory arrest | 2/79 (2.5%) | 2 | 0/123 (0%) | 0 |
| Cardiac disorder | 0/79 (0%) | 0 | 1/123 (0.8%) | 1 |
| Cardiac failure | 0/79 (0%) | 0 | 1/123 (0.8%) | 1 |
| Endocrine disorders | ||||
| Inappropriate antidiuretic hormone secretion | 0/79 (0%) | 0 | 1/123 (0.8%) | 1 |
| Gastrointestinal disorders | ||||
| Nausea | 3/79 (3.8%) | 3 | 2/123 (1.6%) | 2 |
| Diarrhoea | 2/79 (2.5%) | 2 | 2/123 (1.6%) | 2 |
| Vomiting | 2/79 (2.5%) | 2 | 2/123 (1.6%) | 2 |
| Abdominal pain | 1/79 (1.3%) | 1 | 1/123 (0.8%) | 1 |
| Ascites | 1/79 (1.3%) | 1 | 0/123 (0%) | 0 |
| Colitis | 0/79 (0%) | 0 | 1/123 (0.8%) | 1 |
| Dysphagia | 0/79 (0%) | 0 | 1/123 (0.8%) | 1 |
| Enterocolitis haemorrhagic | 0/79 (0%) | 0 | 1/123 (0.8%) | 1 |
| Gastrooesophageal reflux disease | 1/79 (1.3%) | 1 | 0/123 (0%) | 0 |
| Haematemesis | 1/79 (1.3%) | 1 | 0/123 (0%) | 0 |
| Pancreatitis | 1/79 (1.3%) | 1 | 0/123 (0%) | 0 |
| Rectal haemorrhage | 0/79 (0%) | 0 | 1/123 (0.8%) | 1 |
| General disorders | ||||
| Fatigue | 2/79 (2.5%) | 2 | 4/123 (3.3%) | 4 |
| Pyrexia | 3/79 (3.8%) | 3 | 3/123 (2.4%) | 3 |
| Asthenia | 1/79 (1.3%) | 1 | 3/123 (2.4%) | 3 |
| General physical health deterioration | 0/79 (0%) | 0 | 4/123 (3.3%) | 4 |
| Multiple organ dysfunction syndrome | 1/79 (1.3%) | 1 | 1/123 (0.8%) | 1 |
| Hyperthermia | 0/79 (0%) | 0 | 1/123 (0.8%) | 1 |
| Oedema peripheral | 0/79 (0%) | 0 | 1/123 (0.8%) | 1 |
| Strangulated hernia | 0/79 (0%) | 0 | 1/123 (0.8%) | 1 |
| Infections and infestations | ||||
| Pneumonia | 2/79 (2.5%) | 2 | 14/123 (11.4%) | 14 |
| Sepsis | 1/79 (1.3%) | 1 | 12/123 (9.8%) | 12 |
| Bacteraemia | 2/79 (2.5%) | 2 | 3/123 (2.4%) | 3 |
| Influenza | 4/79 (5.1%) | 4 | 1/123 (0.8%) | 1 |
| Parainfluenzae virus infection | 1/79 (1.3%) | 1 | 2/123 (1.6%) | 2 |
| Clostridium difficile infection | 0/79 (0%) | 0 | 2/123 (1.6%) | 2 |
| Escherichia bacteraemia | 0/79 (0%) | 0 | 2/123 (1.6%) | 2 |
| Lung infection | 1/79 (1.3%) | 1 | 1/123 (0.8%) | 1 |
| Adenovirus infection | 1/79 (1.3%) | 1 | 0/123 (0%) | 0 |
| Bronchiolitis | 1/79 (1.3%) | 1 | 0/123 (0%) | 0 |
| Bronchitis | 1/79 (1.3%) | 1 | 0/123 (0%) | 0 |
| Cellulitis | 0/79 (0%) | 0 | 1/123 (0.8%) | 1 |
| Diverticulitis | 0/79 (0%) | 0 | 1/123 (0.8%) | 1 |
| Ear infection | 0/79 (0%) | 0 | 1/123 (0.8%) | 1 |
| Escherichia urinary tract infection | 0/79 (0%) | 0 | 1/123 (0.8%) | 1 |
| Fungal infection | 0/79 (0%) | 0 | 1/123 (0.8%) | 1 |
| Gastroenteritis salmonella | 1/79 (1.3%) | 1 | 0/123 (0%) | 0 |
| H1N1 influenza | 1/79 (1.3%) | 1 | 0/123 (0%) | 0 |
| Pneumocystis jirovecii pneumonia | 1/79 (1.3%) | 1 | 0/123 (0%) | 0 |
| Rhinovirus infection | 1/79 (1.3%) | 1 | 0/123 (0%) | 0 |
| Sinusitis | 0/79 (0%) | 0 | 1/123 (0.8%) | 1 |
| Staphylococcal infection | 1/79 (1.3%) | 1 | 0/123 (0%) | 0 |
| Streptococcal bacteraemia | 0/79 (0%) | 0 | 1/123 (0.8%) | 1 |
| Upper respiratory tract infection | 1/79 (1.3%) | 1 | 0/123 (0%) | 0 |
| Urinary tract infection | 0/79 (0%) | 0 | 1/123 (0.8%) | 1 |
| Injury, poisoning and procedural complications | ||||
| Fall | 2/79 (2.5%) | 2 | 1/123 (0.8%) | 1 |
| Subdural haematoma | 1/79 (1.3%) | 1 | 2/123 (1.6%) | 2 |
| Compression fracture | 2/79 (2.5%) | 2 | 0/123 (0%) | 0 |
| Femur fracture | 0/79 (0%) | 0 | 2/123 (1.6%) | 2 |
| Cervical vertebral fracture | 1/79 (1.3%) | 1 | 0/123 (0%) | 0 |
| Hip fracture | 0/79 (0%) | 0 | 1/123 (0.8%) | 1 |
| Lower limb fracture | 1/79 (1.3%) | 1 | 0/123 (0%) | 0 |
| Overdose | 0/79 (0%) | 0 | 1/123 (0.8%) | 1 |
| Post procedural haemorrhage | 0/79 (0%) | 0 | 1/123 (0.8%) | 1 |
| Procedural haemorrhage | 0/79 (0%) | 0 | 1/123 (0.8%) | 1 |
| Road traffic accident | 0/79 (0%) | 0 | 1/123 (0.8%) | 1 |
| Skin abrasion | 1/79 (1.3%) | 1 | 0/123 (0%) | 0 |
| Investigations | ||||
| Ejection fraction decreased | 1/79 (1.3%) | 1 | 0/123 (0%) | 0 |
| Respiratory syncytial virus test positive | 1/79 (1.3%) | 1 | 0/123 (0%) | 0 |
| Weight decreased | 0/79 (0%) | 0 | 1/123 (0.8%) | 1 |
| Metabolism and nutrition disorders | ||||
| Dehydration | 3/79 (3.8%) | 3 | 3/123 (2.4%) | 3 |
| Hyponatraemia | 2/79 (2.5%) | 2 | 4/123 (3.3%) | 4 |
| Hypercalcaemia | 4/79 (5.1%) | 4 | 0/123 (0%) | 0 |
| Decreased appetite | 1/79 (1.3%) | 1 | 2/123 (1.6%) | 2 |
| Hyperglycaemia | 1/79 (1.3%) | 1 | 2/123 (1.6%) | 2 |
| Diabetic metabolic decompensation | 0/79 (0%) | 0 | 1/123 (0.8%) | 1 |
| Fluid overload | 1/79 (1.3%) | 1 | 0/123 (0%) | 0 |
| Fluid retention | 0/79 (0%) | 0 | 1/123 (0.8%) | 1 |
| Hyperglycaemic hyperosmolar nonketotic syndrome | 1/79 (1.3%) | 1 | 0/123 (0%) | 0 |
| Hyperkalaemia | 0/79 (0%) | 0 | 1/123 (0.8%) | 1 |
| Hypernatraemia | 1/79 (1.3%) | 1 | 0/123 (0%) | 0 |
| Hyperuricaemia | 1/79 (1.3%) | 1 | 0/123 (0%) | 0 |
| Hypocalcaemia | 1/79 (1.3%) | 1 | 0/123 (0%) | 0 |
| Hypophosphataemia | 1/79 (1.3%) | 1 | 0/123 (0%) | 0 |
| Metabolic acidosis | 1/79 (1.3%) | 1 | 0/123 (0%) | 0 |
| Tumour lysis syndrome | 0/79 (0%) | 0 | 1/123 (0.8%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||
| Back pain | 1/79 (1.3%) | 1 | 1/123 (0.8%) | 1 |
| Pathological fracture | 0/79 (0%) | 0 | 2/123 (1.6%) | 2 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Malignant ascites | 1/79 (1.3%) | 1 | 0/123 (0%) | 0 |
| Plasma cell leukaemia | 1/79 (1.3%) | 1 | 0/123 (0%) | 0 |
| Nervous system disorders | ||||
| Syncope | 1/79 (1.3%) | 1 | 2/123 (1.6%) | 2 |
| Encephalopathy | 0/79 (0%) | 0 | 1/123 (0.8%) | 1 |
| Metabolic encephalopathy | 0/79 (0%) | 0 | 1/123 (0.8%) | 1 |
| Peripheral neuropathy | 0/79 (0%) | 0 | 1/123 (0.8%) | 1 |
| Spinal cord compression | 0/79 (0%) | 0 | 1/123 (0.8%) | 1 |
| Psychiatric disorders | ||||
| Confusional state | 4/79 (5.1%) | 4 | 4/123 (3.3%) | 4 |
| Mental status changes | 1/79 (1.3%) | 1 | 4/123 (3.3%) | 4 |
| Agitation | 1/79 (1.3%) | 1 | 0/123 (0%) | 0 |
| Delirium | 1/79 (1.3%) | 1 | 0/123 (0%) | 0 |
| Depression | 0/79 (0%) | 0 | 1/123 (0.8%) | 1 |
| Hallucination | 0/79 (0%) | 0 | 1/123 (0.8%) | 1 |
| Mania | 0/79 (0%) | 0 | 1/123 (0.8%) | 1 |
| Renal and urinary disorders | ||||
| Acute kidney injury | 4/79 (5.1%) | 4 | 3/123 (2.4%) | 3 |
| End stage renal disease | 0/79 (0%) | 0 | 1/123 (0.8%) | 1 |
| Renal failure | 0/79 (0%) | 0 | 1/123 (0.8%) | 1 |
| Renal vein thrombosis | 0/79 (0%) | 0 | 1/123 (0.8%) | 1 |
| Urinary retention | 1/79 (1.3%) | 1 | 0/123 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Dyspnoea | 3/79 (3.8%) | 3 | 1/123 (0.8%) | 1 |
| Epistaxis | 0/79 (0%) | 0 | 2/123 (1.6%) | 2 |
| Pleural effusion | 1/79 (1.3%) | 1 | 1/123 (0.8%) | 1 |
| Pneumonitis | 0/79 (0%) | 0 | 2/123 (1.6%) | 2 |
| Pulmonary embolism | 0/79 (0%) | 0 | 2/123 (1.6%) | 2 |
| Respiratory failure | 1/79 (1.3%) | 1 | 1/123 (0.8%) | 1 |
| Acute pulmonary oedema | 0/79 (0%) | 0 | 1/123 (0.8%) | 1 |
| Acute respiratory failure | 1/79 (1.3%) | 1 | 0/123 (0%) | 0 |
| Bronchopneumopathy | 0/79 (0%) | 0 | 1/123 (0.8%) | 1 |
| Hypoxia | 0/79 (0%) | 0 | 1/123 (0.8%) | 1 |
| Lung disorder | 0/79 (0%) | 0 | 1/123 (0.8%) | 1 |
| Pulmonary oedema | 0/79 (0%) | 0 | 1/123 (0.8%) | 1 |
| Respiratory arrest | 0/79 (0%) | 0 | 1/123 (0.8%) | 1 |
| Skin and subcutaneous tissue disorders | ||||
| Eczema | 0/79 (0%) | 0 | 1/123 (0.8%) | 1 |
| Vascular disorders | ||||
| Circulatory collapse | 0/79 (0%) | 0 | 1/123 (0.8%) | 1 |
| Deep vein thrombosis | 0/79 (0%) | 0 | 1/123 (0.8%) | 1 |
| Haematoma | 0/79 (0%) | 0 | 1/123 (0.8%) | 1 |
| Haemorrhage | 0/79 (0%) | 0 | 1/123 (0.8%) | 1 |
| Orthostatic hypotension | 0/79 (0%) | 0 | 1/123 (0.8%) | 1 |
Other (Not Including Serious) Adverse Events |
||||
| Part 1 | Part 2 | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 79/79 (100%) | 123/123 (100%) | ||
| Blood and lymphatic system disorders | ||||
| Thrombocytopenia | 58/79 (73.4%) | 58 | 91/123 (74%) | 91 |
| Anaemia | 37/79 (46.8%) | 37 | 80/123 (65%) | 80 |
| Neutropenia | 23/79 (29.1%) | 23 | 49/123 (39.8%) | 49 |
| Leukopenia | 20/79 (25.3%) | 20 | 41/123 (33.3%) | 41 |
| Lymphopenia | 11/79 (13.9%) | 11 | 20/123 (16.3%) | 20 |
| Cardiac disorders | ||||
| Tachycardia | 9/79 (11.4%) | 9 | 4/123 (3.3%) | 4 |
| Eye disorders | ||||
| Vision blurred | 10/79 (12.7%) | 10 | 13/123 (10.6%) | 13 |
| Gastrointestinal disorders | ||||
| Nausea | 60/79 (75.9%) | 60 | 88/123 (71.5%) | 88 |
| Diarrhoea | 35/79 (44.3%) | 35 | 57/123 (46.3%) | 57 |
| Vomiting | 37/79 (46.8%) | 37 | 47/123 (38.2%) | 47 |
| Constipation | 21/79 (26.6%) | 21 | 27/123 (22%) | 27 |
| Abdominal pain | 7/79 (8.9%) | 7 | 12/123 (9.8%) | 12 |
| General disorders | ||||
| Fatigue | 55/79 (69.6%) | 55 | 77/123 (62.6%) | 77 |
| Pyrexia | 10/79 (12.7%) | 10 | 18/123 (14.6%) | 18 |
| Asthenia | 5/79 (6.3%) | 5 | 19/123 (15.4%) | 19 |
| Oedema peripheral | 5/79 (6.3%) | 5 | 14/123 (11.4%) | 14 |
| Chills | 6/79 (7.6%) | 6 | 4/123 (3.3%) | 4 |
| Malaise | 2/79 (2.5%) | 2 | 8/123 (6.5%) | 8 |
| Gait disturbance | 0/79 (0%) | 0 | 7/123 (5.7%) | 7 |
| Infections and infestations | ||||
| Upper respiratory tract infection | 10/79 (12.7%) | 10 | 17/123 (13.8%) | 17 |
| Pneumonia | 3/79 (3.8%) | 3 | 10/123 (8.1%) | 10 |
| Urinary tract infection | 6/79 (7.6%) | 6 | 4/123 (3.3%) | 4 |
| Injury, poisoning and procedural complications | ||||
| Fall | 4/79 (5.1%) | 4 | 13/123 (10.6%) | 13 |
| Investigations | ||||
| Weight decreased | 39/79 (49.4%) | 39 | 61/123 (49.6%) | 61 |
| Alanine aminotransferase increased | 6/79 (7.6%) | 6 | 13/123 (10.6%) | 13 |
| Aspartate aminotransferase increased | 3/79 (3.8%) | 3 | 11/123 (8.9%) | 11 |
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 43/79 (54.4%) | 43 | 68/123 (55.3%) | 68 |
| Hyponatraemia | 34/79 (43%) | 34 | 45/123 (36.6%) | 45 |
| Hyperglycaemia | 16/79 (20.3%) | 16 | 15/123 (12.2%) | 15 |
| Hypokalaemia | 5/79 (6.3%) | 5 | 24/123 (19.5%) | 24 |
| Dehydration | 15/79 (19%) | 15 | 10/123 (8.1%) | 10 |
| Hypocalcaemia | 7/79 (8.9%) | 7 | 13/123 (10.6%) | 13 |
| Hypomagnesaemia | 10/79 (12.7%) | 10 | 10/123 (8.1%) | 10 |
| Hypophosphataemia | 6/79 (7.6%) | 6 | 8/123 (6.5%) | 8 |
| Hypercreatininaemia | 6/79 (7.6%) | 6 | 6/123 (4.9%) | 6 |
| Hypercalcaemia | 6/79 (7.6%) | 6 | 5/123 (4.1%) | 5 |
| Hyperkalaemia | 1/79 (1.3%) | 1 | 10/123 (8.1%) | 10 |
| Musculoskeletal and connective tissue disorders | ||||
| Back pain | 9/79 (11.4%) | 9 | 10/123 (8.1%) | 10 |
| Bone pain | 7/79 (8.9%) | 7 | 11/123 (8.9%) | 11 |
| Hypercreatinaemia | 9/79 (11.4%) | 9 | 6/123 (4.9%) | 6 |
| Arthralgia | 6/79 (7.6%) | 6 | 6/123 (4.9%) | 6 |
| Muscle spasms | 4/79 (5.1%) | 4 | 8/123 (6.5%) | 8 |
| Muscular weakness | 6/79 (7.6%) | 6 | 4/123 (3.3%) | 4 |
| Pain in extremity | 4/79 (5.1%) | 4 | 4/123 (3.3%) | 4 |
| Nervous system disorders | ||||
| Dizziness | 12/79 (15.2%) | 12 | 19/123 (15.4%) | 19 |
| Headache | 10/79 (12.7%) | 10 | 11/123 (8.9%) | 11 |
| Dysgeusia | 10/79 (12.7%) | 10 | 10/123 (8.1%) | 10 |
| Peripheral neuropathy | 7/79 (8.9%) | 7 | 8/123 (6.5%) | 8 |
| Psychiatric disorders | ||||
| Insomnia | 11/79 (13.9%) | 11 | 22/123 (17.9%) | 22 |
| Confusional state | 9/79 (11.4%) | 9 | 11/123 (8.9%) | 11 |
| Anxiety | 4/79 (5.1%) | 4 | 8/123 (6.5%) | 8 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Dyspnoea | 23/79 (29.1%) | 23 | 28/123 (22.8%) | 28 |
| Cough | 12/79 (15.2%) | 12 | 18/123 (14.6%) | 18 |
| Epistaxis | 11/79 (13.9%) | 11 | 13/123 (10.6%) | 13 |
| Productive cough | 4/79 (5.1%) | 4 | 3/123 (2.4%) | 3 |
| Skin and subcutaneous tissue disorders | ||||
| Alopecia | 4/79 (5.1%) | 4 | 3/123 (2.4%) | 3 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Jatin Shah, MD |
|---|---|
| Organization | Karyopharm Therapeutics Inc. |
| Phone | (617) 658-0600 |
| jshah@karyopharm.com |
Responsible Party:
Karyopharm Therapeutics Inc
ClinicalTrials.gov Identifier:
NCT02336815
Other Study ID Numbers:
- KCP-330-012
First Posted:
Jan 13, 2015
Last Update Posted:
Nov 20, 2020
Last Verified:
Nov 1, 2020