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Selinexor Treatment of Refractory Myeloma (STORM)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02336815
Recruitment Status : Completed
First Posted : January 13, 2015
Results First Posted : August 13, 2020
Last Update Posted : January 26, 2023
Sponsor:
Information provided by (Responsible Party):
Karyopharm Therapeutics Inc

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Multiple Myeloma
Interventions Drug: Selinexor
Drug: Dexamethasone
Enrollment 202
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 Details 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
Hide 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
Reason Not Completed
Disease Progression             45             70
Adverse Event             18             39
Physician Decision             11             4
Withdrawal by Subject             3             2
Lost to Follow-up             1             3
Other             1             5
Arm/Group Title Part 1 Part 2 Total
Hide 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 Number of Baseline Participants 79 123 202
Hide Baseline 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.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 79 participants 123 participants 202 participants
62.9  (8.79) 64.5  (9.41) 63.9  (9.18)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 79 participants 123 participants 202 participants
Female
42
  53.2%
52
  42.3%
94
  46.5%
Male
37
  46.8%
71
  57.7%
108
  53.5%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 79 participants 123 participants 202 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)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 79 participants 123 participants 202 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
2
   1.6%
2
   1.0%
Native Hawaiian or Other Pacific Islander
0
   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
   5.0%
Unknown or Not Reported
1
   1.3%
5
   4.1%
6
   3.0%
1.Primary Outcome
Title Part 2: Percentage of Participants With Overall Response Rate (ORR) Per International MyelomaWorking Group (IMWG) as Assessed by an Independent Review Committee (IRC)
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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).
Overall Number of Participants Analyzed 122
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
26.2
(18.7 to 35.0)
2.Secondary Outcome
Title Part 1: Duration of Response (DoR) Per IMWG as Assessed by IRC
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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).
Overall Number of Participants Analyzed 16
Median (95% Confidence Interval)
Unit of Measure: Months
6.2
(3.6 to 9.8)
3.Secondary Outcome
Title Part 2: Duration of Response (DoR) Per IMWG as Assessed by an IRC
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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).
Overall Number of Participants Analyzed 32
Median (95% Confidence Interval)
Unit of Measure: Months
4.4
(3.7 to 10.8)
4.Secondary Outcome
Title Part 1: Percentage of Participants With Clinical Benefit Rate (CBR) ) Per IMWG as Assessed by IRC
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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).
Overall Number of Participants Analyzed 79
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
31.6
(21.6 to 43.1)
5.Secondary Outcome
Title Part 2: Percentage of Participants With Clinical Benefit Rate (CBR) Per IMWG as Assessed by IRC
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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).
Overall Number of Participants Analyzed 122
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
39.3
(30.6 to 48.6)
6.Secondary Outcome
Title Part 1: Duration of Clinical Benefit Per IMWG as Assessed by IRC
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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).
Overall Number of Participants Analyzed 25
Median (95% Confidence Interval)
Unit of Measure: Months
5.6
(4.4 to 10.3)
7.Secondary Outcome
Title Part 2: Duration of Clinical Benefit Per IMWG as Assessed by IRC
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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).
Overall Number of Participants Analyzed 48
Median (95% Confidence Interval)
Unit of Measure: Months
3.8
(3.2 to 10.9)
8.Secondary Outcome
Title Part 2: Disease Control Rate (DCR)
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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).
Overall Number of Participants Analyzed 122
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
44.3
(35.3 to 53.5)
9.Secondary Outcome
Title Part 1: Progression Free Survival (PFS) Per IMWG as Assessed by IRC
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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).
Overall Number of Participants Analyzed 79
Median (95% Confidence Interval)
Unit of Measure: Months
4.7
(3.3 to 7.6)
10.Secondary Outcome
Title Part 2: Progression Free Survival (PFS) Per IMWG as Assessed by IRC
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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).
Overall Number of Participants Analyzed 122
Median (95% Confidence Interval)
Unit of Measure: Months
3.7
(2.8 to 4.7)
11.Secondary Outcome
Title Part 1: Time to Progression (TTP) Per IMWG as Assessed by IRC
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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).
Overall Number of Participants Analyzed 79
Median (95% Confidence Interval)
Unit of Measure: Months
5.5
(3.3 to 10.7)
12.Secondary Outcome
Title Part 2: Time to Progression (TTP) Per IMWG as Assessed by IRC
Hide 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)
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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
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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).
Overall Number of Participants Analyzed 122
Median (95% Confidence Interval)
Unit of Measure: Months
4.1
(3.0 to 6.2)
13.Secondary Outcome
Title Part 1: Time to Next Treatment (TTNT)
Hide 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)
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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
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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).
Overall Number of Participants Analyzed 79
Median (95% Confidence Interval)
Unit of Measure: Months
2.6
(1.8 to 4.2)
14.Secondary Outcome
Title Part 2: Time to Next Treatment (TTNT)
Hide 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)
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Hide 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
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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).
Overall Number of Participants Analyzed 122
Median (95% Confidence Interval)
Unit of Measure: Months
3.2
(2.6 to 3.8)
15.Secondary Outcome
Title Part 1: Overall Survival (OS)
Hide 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)
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Hide 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
Hide 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).
Overall Number of Participants Analyzed 79
Median (95% Confidence Interval)
Unit of Measure: Months
7.3
(5.8 to 10.9)
16.Secondary Outcome
Title Part 2: Overall Survival (OS)
Hide 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)
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Hide 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
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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).
Overall Number of Participants Analyzed 122
Median (95% Confidence Interval)
Unit of Measure: Months
8.4
(6.2 to 11.2)
17.Secondary Outcome
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
Hide 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)
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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
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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).
Overall Number of Participants Analyzed 107
Mean (Standard Deviation)
Unit of Measure: Score on a Scale
Trial Outcomes Index Score: Baseline Number Analyzed 107 participants
67.5  (19.20)
Trial Outcomes Index Score: Change at C2D1 Number Analyzed 76 participants
-6.1  (18.43)
Trial Outcomes Index Score: Change at C3D1 Number Analyzed 50 participants
-8.5  (15.50)
Trial Outcomes Index Score: Change at C4D1 Number Analyzed 31 participants
-9.1  (16.79)
Trial Outcomes Index Score: Change at C5D1 Number Analyzed 26 participants
-6.9  (12.06)
Trial Outcomes Index Score: Change at C6D1 Number Analyzed 19 participants
-8.3  (15.07)
Trial Outcomes Index Score: Change at C7D1 Number Analyzed 13 participants
-7.5  (19.26)
Trial Outcomes Index Score: Change at C8D1 Number Analyzed 5 participants
-15.4  (24.59)
Trial Outcomes Index Score: Change at C9D1 Number Analyzed 3 participants
-4.7  (14.84)
Trial Outcomes Index Score: Change at C10D1 Number Analyzed 3 participants
-4.0  (5.29)
Trial Outcomes Index Score: Change at C11D1 Number Analyzed 1 participants
3.0 [1]   (NA)
Trial Outcomes Index Score: Change at C12D1 Number Analyzed 1 participants
3.0 [1]   (NA)
Trial Outcomes Index Score: Change at C13D1 Number Analyzed 1 participants
-23.0 [1]   (NA)
Trial Outcomes Index Score: Change at C14D1 Number Analyzed 1 participants
14.0 [1]   (NA)
Trial Outcomes Index Score: Change at C15D1 Number Analyzed 1 participants
1.0 [1]   (NA)
Trial Outcomes Index Score: Change at C16D1 Number Analyzed 1 participants
4.0 [1]   (NA)
Trial Outcomes Index Score: Change at C17D1 Number Analyzed 0 participants
Trial Outcomes Index Score: Change at C18D1 Number Analyzed 0 participants
Trial Outcomes Index Score: Change at C19D1 Number Analyzed 0 participants
Trial Outcomes Index Score: Change at C20D1 Number Analyzed 0 participants
[1]
Standard deviation was not estimated due to single participant.
18.Secondary Outcome
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
Hide 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)
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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
Hide 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).
Overall Number of Participants Analyzed 79 123
Measure Type: Count of Participants
Unit of Measure: Participants
75
  94.9%
115
  93.5%
19.Secondary Outcome
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
Hide 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)
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Hide 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
Hide 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).
Overall Number of Participants Analyzed 79 123
Measure Type: Count of Participants
Unit of Measure: Participants
69
  87.3%
110
  89.4%
20.Secondary Outcome
Title Apparent Clearance (CL/F) of Selinexor in Plasma
Hide 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
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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
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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).
Overall Number of Participants Analyzed 79
Mean (Standard Deviation)
Unit of Measure: Liters/Hour
16.6  (2.8)
21.Secondary Outcome
Title Volume of Distribution (V/F) of Selinexor in Plasma
Hide 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
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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
Hide 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).
Overall Number of Participants Analyzed 79
Mean (Standard Deviation)
Unit of Measure: Liter
145.6  (28.2)
Time Frame Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Part 1 Part 2
Hide 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 (%) Affected / at Risk (%)
Total   20/79 (25.32%)      28/123 (22.76%)    
Hide Serious Adverse Events
Part 1 Part 2
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   45/79 (56.96%)      78/123 (63.41%)    
Blood and lymphatic system disorders     
Thrombocytopenia † 1  5/79 (6.33%)  5 3/123 (2.44%)  3
Anaemia † 1  2/79 (2.53%)  2 4/123 (3.25%)  4
Febrile neutropenia † 1  3/79 (3.80%)  3 0/123 (0.00%)  0
Leukopenia † 1  1/79 (1.27%)  1 0/123 (0.00%)  0
Lymphopenia † 1  1/79 (1.27%)  1 0/123 (0.00%)  0
Neutropenia † 1  0/79 (0.00%)  0 1/123 (0.81%)  1
Cardiac disorders     
Cardio-respiratory arrest † 1  2/79 (2.53%)  2 0/123 (0.00%)  0
Cardiac disorder † 1  0/79 (0.00%)  0 1/123 (0.81%)  1
Cardiac failure † 1  0/79 (0.00%)  0 1/123 (0.81%)  1
Endocrine disorders     
Inappropriate antidiuretic hormone secretion † 1  0/79 (0.00%)  0 1/123 (0.81%)  1
Gastrointestinal disorders     
Nausea † 1  3/79 (3.80%)  3 2/123 (1.63%)  2
Diarrhoea † 1  2/79 (2.53%)  2 2/123 (1.63%)  2
Vomiting † 1  2/79 (2.53%)  2 2/123 (1.63%)  2
Abdominal pain † 1  1/79 (1.27%)  1 1/123 (0.81%)  1
Ascites † 1  1/79 (1.27%)  1 0/123 (0.00%)  0
Colitis † 1  0/79 (0.00%)  0 1/123 (0.81%)  1
Dysphagia † 1  0/79 (0.00%)  0 1/123 (0.81%)  1
Enterocolitis haemorrhagic † 1  0/79 (0.00%)  0 1/123 (0.81%)  1
Gastrooesophageal reflux disease † 2  1/79 (1.27%)  1 0/123 (0.00%)  0
Haematemesis † 2  1/79 (1.27%)  1 0/123 (0.00%)  0
Pancreatitis † 2  1/79 (1.27%)  1 0/123 (0.00%)  0
Rectal haemorrhage † 2  0/79 (0.00%)  0 1/123 (0.81%)  1
General disorders     
Fatigue † 2  2/79 (2.53%)  2 4/123 (3.25%)  4
Pyrexia † 2  3/79 (3.80%)  3 3/123 (2.44%)  3
Asthenia † 2  1/79 (1.27%)  1 3/123 (2.44%)  3
General physical health deterioration † 2  0/79 (0.00%)  0 4/123 (3.25%)  4
Multiple organ dysfunction syndrome † 2  1/79 (1.27%)  1 1/123 (0.81%)  1
Hyperthermia † 2  0/79 (0.00%)  0 1/123 (0.81%)  1
Oedema peripheral † 2  0/79 (0.00%)  0 1/123 (0.81%)  1
Strangulated hernia † 2  0/79 (0.00%)  0 1/123 (0.81%)  1
Infections and infestations     
Pneumonia † 2  2/79 (2.53%)  2 14/123 (11.38%)  14
Sepsis † 1  1/79 (1.27%)  1 12/123 (9.76%)  12
Bacteraemia † 2  2/79 (2.53%)  2 3/123 (2.44%)  3
Influenza † 2  4/79 (5.06%)  4 1/123 (0.81%)  1
Parainfluenzae virus infection † 2  1/79 (1.27%)  1 2/123 (1.63%)  2
Clostridium difficile infection † 2  0/79 (0.00%)  0 2/123 (1.63%)  2
Escherichia bacteraemia † 2  0/79 (0.00%)  0 2/123 (1.63%)  2
Lung infection † 2  1/79 (1.27%)  1 1/123 (0.81%)  1
Adenovirus infection † 2  1/79 (1.27%)  1 0/123 (0.00%)  0
Bronchiolitis † 2  1/79 (1.27%)  1 0/123 (0.00%)  0
Bronchitis † 2  1/79 (1.27%)  1 0/123 (0.00%)  0
Cellulitis † 1  0/79 (0.00%)  0 1/123 (0.81%)  1
Diverticulitis † 2  0/79 (0.00%)  0 1/123 (0.81%)  1
Ear infection † 2  0/79 (0.00%)  0 1/123 (0.81%)  1
Escherichia urinary tract infection † 2  0/79 (0.00%)  0 1/123 (0.81%)  1
Fungal infection † 2  0/79 (0.00%)  0 1/123 (0.81%)  1
Gastroenteritis salmonella † 2  1/79 (1.27%)  1 0/123 (0.00%)  0
H1N1 influenza † 2  1/79 (1.27%)  1 0/123 (0.00%)  0
Pneumocystis jirovecii pneumonia † 2  1/79 (1.27%)  1 0/123 (0.00%)  0
Rhinovirus infection † 2  1/79 (1.27%)  1 0/123 (0.00%)  0
Sinusitis † 2  0/79 (0.00%)  0 1/123 (0.81%)  1
Staphylococcal infection † 2  1/79 (1.27%)  1 0/123 (0.00%)  0
Streptococcal bacteraemia † 2  0/79 (0.00%)  0 1/123 (0.81%)  1
Upper respiratory tract infection † 2  1/79 (1.27%)  1 0/123 (0.00%)  0
Urinary tract infection † 2  0/79 (0.00%)  0 1/123 (0.81%)  1
Injury, poisoning and procedural complications     
Fall † 2  2/79 (2.53%)  2 1/123 (0.81%)  1
Subdural haematoma † 2  1/79 (1.27%)  1 2/123 (1.63%)  2
Compression fracture † 2  2/79 (2.53%)  2 0/123 (0.00%)  0
Femur fracture † 1  0/79 (0.00%)  0 2/123 (1.63%)  2
Cervical vertebral fracture † 2  1/79 (1.27%)  1 0/123 (0.00%)  0
Hip fracture † 2  0/79 (0.00%)  0 1/123 (0.81%)  1
Lower limb fracture † 2  1/79 (1.27%)  1 0/123 (0.00%)  0
Overdose † 2  0/79 (0.00%)  0 1/123 (0.81%)  1
Post procedural haemorrhage † 2  0/79 (0.00%)  0 1/123 (0.81%)  1
Procedural haemorrhage † 2  0/79 (0.00%)  0 1/123 (0.81%)  1
Road traffic accident † 2  0/79 (0.00%)  0 1/123 (0.81%)  1
Skin abrasion † 2  1/79 (1.27%)  1 0/123 (0.00%)  0
Investigations     
Ejection fraction decreased † 2  1/79 (1.27%)  1 0/123 (0.00%)  0
Respiratory syncytial virus test positive † 2  1/79 (1.27%)  1 0/123 (0.00%)  0
Weight decreased † 2  0/79 (0.00%)  0 1/123 (0.81%)  1
Metabolism and nutrition disorders     
Dehydration † 2  3/79 (3.80%)  3 3/123 (2.44%)  3
Hyponatraemia † 2  2/79 (2.53%)  2 4/123 (3.25%)  4
Hypercalcaemia † 2  4/79 (5.06%)  4 0/123 (0.00%)  0
Decreased appetite † 1  1/79 (1.27%)  1 2/123 (1.63%)  2
Hyperglycaemia † 2  1/79 (1.27%)  1 2/123 (1.63%)  2
Diabetic metabolic decompensation † 2  0/79 (0.00%)  0 1/123 (0.81%)  1
Fluid overload † 2  1/79 (1.27%)  1 0/123 (0.00%)  0
Fluid retention † 2  0/79 (0.00%)  0 1/123 (0.81%)  1
Hyperglycaemic hyperosmolar nonketotic syndrome † 2  1/79 (1.27%)  1 0/123 (0.00%)  0
Hyperkalaemia † 2  0/79 (0.00%)  0 1/123 (0.81%)  1
Hypernatraemia † 2  1/79 (1.27%)  1 0/123 (0.00%)  0
Hyperuricaemia † 1  1/79 (1.27%)  1 0/123 (0.00%)  0
Hypocalcaemia † 2  1/79 (1.27%)  1 0/123 (0.00%)  0
Hypophosphataemia † 2  1/79 (1.27%)  1 0/123 (0.00%)  0
Metabolic acidosis † 2  1/79 (1.27%)  1 0/123 (0.00%)  0
Tumour lysis syndrome † 2  0/79 (0.00%)  0 1/123 (0.81%)  1
Musculoskeletal and connective tissue disorders     
Back pain † 2  1/79 (1.27%)  1 1/123 (0.81%)  1
Pathological fracture † 2  0/79 (0.00%)  0 2/123 (1.63%)  2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Malignant ascites † 2  1/79 (1.27%)  1 0/123 (0.00%)  0
Plasma cell leukaemia † 2  1/79 (1.27%)  1 0/123 (0.00%)  0
Nervous system disorders     
Syncope † 2  1/79 (1.27%)  1 2/123 (1.63%)  2
Encephalopathy † 2  0/79 (0.00%)  0 1/123 (0.81%)  1
Metabolic encephalopathy † 2  0/79 (0.00%)  0 1/123 (0.81%)  1
Peripheral neuropathy † 2  0/79 (0.00%)  0 1/123 (0.81%)  1
Spinal cord compression † 2  0/79 (0.00%)  0 1/123 (0.81%)  1
Psychiatric disorders     
Confusional state † 2  4/79 (5.06%)  4 4/123 (3.25%)  4
Mental status changes † 2  1/79 (1.27%)  1 4/123 (3.25%)  4
Agitation † 2  1/79 (1.27%)  1 0/123 (0.00%)  0
Delirium † 2  1/79 (1.27%)  1 0/123 (0.00%)  0
Depression † 2  0/79 (0.00%)  0 1/123 (0.81%)  1
Hallucination † 1  0/79 (0.00%)  0 1/123 (0.81%)  1
Mania † 2  0/79 (0.00%)  0 1/123 (0.81%)  1
Renal and urinary disorders     
Acute kidney injury † 2  4/79 (5.06%)  4 3/123 (2.44%)  3
End stage renal disease † 2  0/79 (0.00%)  0 1/123 (0.81%)  1
Renal failure † 2  0/79 (0.00%)  0 1/123 (0.81%)  1
Renal vein thrombosis † 2  0/79 (0.00%)  0 1/123 (0.81%)  1
Urinary retention † 2  1/79 (1.27%)  1 0/123 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Dyspnoea † 2  3/79 (3.80%)  3 1/123 (0.81%)  1
Epistaxis † 2  0/79 (0.00%)  0 2/123 (1.63%)  2
Pleural effusion † 2  1/79 (1.27%)  1 1/123 (0.81%)  1
Pneumonitis † 2  0/79 (0.00%)  0 2/123 (1.63%)  2
Pulmonary embolism † 2  0/79 (0.00%)  0 2/123 (1.63%)  2
Respiratory failure † 2  1/79 (1.27%)  1 1/123 (0.81%)  1
Acute pulmonary oedema † 2  0/79 (0.00%)  0 1/123 (0.81%)  1
Acute respiratory failure † 2  1/79 (1.27%)  1 0/123 (0.00%)  0
Bronchopneumopathy † 1  0/79 (0.00%)  0 1/123 (0.81%)  1
Hypoxia † 2  0/79 (0.00%)  0 1/123 (0.81%)  1
Lung disorder † 2  0/79 (0.00%)  0 1/123 (0.81%)  1
Pulmonary oedema † 2  0/79 (0.00%)  0 1/123 (0.81%)  1
Respiratory arrest † 2  0/79 (0.00%)  0 1/123 (0.81%)  1
Skin and subcutaneous tissue disorders     
Eczema † 2  0/79 (0.00%)  0 1/123 (0.81%)  1
Vascular disorders     
Circulatory collapse † 1  0/79 (0.00%)  0 1/123 (0.81%)  1
Deep vein thrombosis † 2  0/79 (0.00%)  0 1/123 (0.81%)  1
Haematoma † 2  0/79 (0.00%)  0 1/123 (0.81%)  1
Haemorrhage † 2  0/79 (0.00%)  0 1/123 (0.81%)  1
Orthostatic hypotension † 2  0/79 (0.00%)  0 1/123 (0.81%)  1
1
Term from vocabulary, MedDRA (20.1)
2
Term from vocabulary, MedDRA (22.0)
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Part 1 Part 2
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   79/79 (100.00%)      123/123 (100.00%)    
Blood and lymphatic system disorders     
Thrombocytopenia † 1  58/79 (73.42%)  58 91/123 (73.98%)  91
Anaemia † 1  37/79 (46.84%)  37 80/123 (65.04%)  80
Neutropenia † 1  23/79 (29.11%)  23 49/123 (39.84%)  49
Leukopenia † 1  20/79 (25.32%)  20 41/123 (33.33%)  41
Lymphopenia † 2  11/79 (13.92%)  11 20/123 (16.26%)  20
Cardiac disorders     
Tachycardia † 1  9/79 (11.39%)  9 4/123 (3.25%)  4
Eye disorders     
Vision blurred † 1  10/79 (12.66%)  10 13/123 (10.57%)  13
Gastrointestinal disorders     
Nausea † 1  60/79 (75.95%)  60 88/123 (71.54%)  88
Diarrhoea † 1  35/79 (44.30%)  35 57/123 (46.34%)  57
Vomiting † 2  37/79 (46.84%)  37 47/123 (38.21%)  47
Constipation † 2  21/79 (26.58%)  21 27/123 (21.95%)  27
Abdominal pain † 2  7/79 (8.86%)  7 12/123 (9.76%)  12
General disorders     
Fatigue † 2  55/79 (69.62%)  55 77/123 (62.60%)  77
Pyrexia † 2  10/79 (12.66%)  10 18/123 (14.63%)  18
Asthenia † 2  5/79 (6.33%)  5 19/123 (15.45%)  19
Oedema peripheral † 1  5/79 (6.33%)  5 14/123 (11.38%)  14
Chills † 1  6/79 (7.59%)  6 4/123 (3.25%)  4
Malaise † 1  2/79 (2.53%)  2 8/123 (6.50%)  8
Gait disturbance † 2  0/79 (0.00%)  0 7/123 (5.69%)  7
Infections and infestations     
Upper respiratory tract infection † 1  10/79 (12.66%)  10 17/123 (13.82%)  17
Pneumonia † 1  3/79 (3.80%)  3 10/123 (8.13%)  10
Urinary tract infection † 1  6/79 (7.59%)  6 4/123 (3.25%)  4
Injury, poisoning and procedural complications     
Fall † 2  4/79 (5.06%)  4 13/123 (10.57%)  13
Investigations     
Weight decreased † 2  39/79 (49.37%)  39 61/123 (49.59%)  61
Alanine aminotransferase increased † 1  6/79 (7.59%)  6 13/123 (10.57%)  13
Aspartate aminotransferase increased † 1  3/79 (3.80%)  3 11/123 (8.94%)  11
Metabolism and nutrition disorders     
Decreased appetite † 2  43/79 (54.43%)  43 68/123 (55.28%)  68
Hyponatraemia † 2  34/79 (43.04%)  34 45/123 (36.59%)  45
Hyperglycaemia † 2  16/79 (20.25%)  16 15/123 (12.20%)  15
Hypokalaemia † 2  5/79 (6.33%)  5 24/123 (19.51%)  24
Dehydration † 2  15/79 (18.99%)  15 10/123 (8.13%)  10
Hypocalcaemia † 2  7/79 (8.86%)  7 13/123 (10.57%)  13
Hypomagnesaemia † 2  10/79 (12.66%)  10 10/123 (8.13%)  10
Hypophosphataemia † 2  6/79 (7.59%)  6 8/123 (6.50%)  8
Hypercreatininaemia † 2  6/79 (7.59%)  6 6/123 (4.88%)  6
Hypercalcaemia † 2  6/79 (7.59%)  6 5/123 (4.07%)  5
Hyperkalaemia † 2  1/79 (1.27%)  1 10/123 (8.13%)  10
Musculoskeletal and connective tissue disorders     
Back pain † 2  9/79 (11.39%)  9 10/123 (8.13%)  10
Bone pain † 2  7/79 (8.86%)  7 11/123 (8.94%)  11
Hypercreatinaemia † 2  9/79 (11.39%)  9 6/123 (4.88%)  6
Arthralgia † 1  6/79 (7.59%)  6 6/123 (4.88%)  6
Muscle spasms † 2  4/79 (5.06%)  4 8/123 (6.50%)  8
Muscular weakness † 2  6/79 (7.59%)  6 4/123 (3.25%)  4
Pain in extremity † 2  4/79 (5.06%)  4 4/123 (3.25%)  4
Nervous system disorders     
Dizziness † 2  12/79 (15.19%)  12 19/123 (15.45%)  19
Headache † 2  10/79 (12.66%)  10 11/123 (8.94%)  11
Dysgeusia † 2  10/79 (12.66%)  10 10/123 (8.13%)  10
Peripheral neuropathy † 2  7/79 (8.86%)  7 8/123 (6.50%)  8
Psychiatric disorders     
Insomnia † 2  11/79 (13.92%)  11 22/123 (17.89%)  22
Confusional state † 2  9/79 (11.39%)  9 11/123 (8.94%)  11
Anxiety † 2  4/79 (5.06%)  4 8/123 (6.50%)  8
Respiratory, thoracic and mediastinal disorders     
Dyspnoea † 2  23/79 (29.11%)  23 28/123 (22.76%)  28
Cough † 2  12/79 (15.19%)  12 18/123 (14.63%)  18
Epistaxis † 2  11/79 (13.92%)  11 13/123 (10.57%)  13
Productive cough † 2  4/79 (5.06%)  4 3/123 (2.44%)  3
Skin and subcutaneous tissue disorders     
Alopecia † 2  4/79 (5.06%)  4 3/123 (2.44%)  3
1
Term from vocabulary, MedDRA (20.1)
2
Term from vocabulary, MedDRA (22.0)
†
Indicates events were collected by systematic assessment
[Not Specified]
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
Layout table for Results Point of Contact information
Name/Title: Jatin Shah, MD
Organization: Karyopharm Therapeutics Inc.
Phone: (617) 658-0600
EMail: jshah@karyopharm.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Karyopharm Therapeutics Inc
ClinicalTrials.gov Identifier: NCT02336815    
Other Study ID Numbers: KCP-330-012
First Submitted: January 8, 2015
First Posted: January 13, 2015
Results First Submitted: July 24, 2020
Results First Posted: August 13, 2020
Last Update Posted: January 26, 2023