Trial Outcomes & Findings for Safety Study of the Selective Inhibitor of Nuclear Export (SINE) KPT-330 in Patients With Advanced Hematological Cancer (NCT NCT01607892)
NCT ID: NCT01607892
Last Updated: 2023-01-26
Results Overview
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product during the course of a study and which does not necessarily have to have a causal relationship with this treatment. An Serious adverse event (SAE) was an AE resulting in any of the following outcomes: death; life-threatening event; required or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly. TEAEs are any untoward medical incidence in a participant during administered study treatment, whether or not these events were related to study treatment.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
286 participants
Primary outcome timeframe
From first dose of study drug administration to end of treatment (up to 27 months)
Results posted on
2023-01-26
Participant Flow
The study was conducted at 12 sites in United States, Canada and Europe between 23 July 2012 (first participant treated) and 13 October 2015 (last participant completed).
A total of 286 participants were enrolled out of which 1 participants with MM never treated due to disease progression prior to dose initiation and 285 participants received treatment in 11 different schedules. The schedules were either 28 days (Schedules 1-7, 9-11) or 21 days (Schedule 8) per cycle and participants were treated once weekly (Schedule 7), twice weekly (Schedules 3-6, 8-11) or three times weekly alternating with 2 times weekly (Schedules 1, 2).
Participant milestones
| Measure |
Diffuse Large B-cell Lymphoma (DLBCL)
Participants with DLBCL received Selinexor in different Schedules; Schedule 1: \<= 12 milligram per square meter (mg/m\^2) per orally (PO) alternating 3 times per week with twice weekly dosing (1 day between doses); Schedule 2: \> 12 mg/m\^2 PO 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 8: \>=40 mg/m\^2 PO twice weekly (1 day between doses) during Weeks 1 and 2; Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab intravenous (IV) once weekly for Weeks 1-4 during different cycles. Each cycle was of 28 days (Schedule 8: 21 days of cycle) or 10 scheduled selinexor doses.
|
Non-Hodgkin Lymphoma (NHL) Excluding DLBCL
Participants with NHL received Selinexor in different Schedules; Schedule 1: \<= 12 mg/m\^2 PO alternating 3 times per week with twice weekly dosing (1 day between doses); Schedule 2: \> 12 mg/m\^2 PO 3 times weekly for week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs 1 day apart (Schedule 3); Schedule 7: \>=45 mg/m\^2 PO once weekly (6 days between doses) to evaluate vs twice weekly (Schedules 3, 4, 5, and 6); Schedule 8: \>=40 mg/m\^2 PO twice weekly \[1 Day between doses\] during weeks 1 and 2; Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab IV once weekly for Weeks 1-4) during different cycles. Each cycle was of 28 days (Schedule 8: 21 days of cycle) or 10 scheduled selinexor doses.
|
Multiple Myeloma (MM)
Participants with MM received Selinexor in different Schedules; Schedule 1: \<= 12 mg/m\^2 PO alternating 3 times per week with twice weekly dosing (1 Day between doses); Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; 3 doses (36 mg/m\^2 total) in the 1-week run-in period; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 6: \>= 35 mg/m\^2 PO twice weekly with dexamethasone (20 mg twice weekly) on Days of twice weekly Selinexor dosing; Schedule 11: Group A: 40 mg; Group B: 60 mg; Group C: 80 mg twice weekly (Weeks 1, 2, and 3) at 3 fixed dose levels during different cycles. Each cycle was of 28 days or 10 scheduled selinexor doses.
|
Acute Myeloid Leukemia (AML)
Participants with AML received Selinexor in different Schedules; Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3), Schedule 7: \>=45 mg/m\^2 PO once weekly (6 Days between doses) to evaluate vs. twice weekly (Schedules 3, 4, 5, and 6); Schedule 8: \>=40 mg/m\^2 PO twice weekly (1 Day between doses) during Weeks 1 and 2; Schedule 10: \>= 55 mg/m\^2 PO twice weekly PO (Weeks 1 and 2) in participants with AML/18-Day treatment-free interval) during different cycles. Each cycle was of 28 days (for schedule 8: 21-day of cycle) or 10 scheduled selinexor doses.
|
Other Hematological Malignancies (ALL, CML and CLL)
Participants with other hematological malignancies (Acute lymphoblastic leukemia \[ALL\], Chronic myelogenous leukemia \[CML\] and chronic lymphocytic leukemia \[CLL\]) received Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly \[1 day between doses\]; Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 7: \>=45 mg/m\^2 PO once weekly (6 Days between doses) to evaluate vs. twice weekly (Schedules 3, 4, 5, and 6); Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab IV once weekly for Weeks 1-4 during different cycles. Each cycle was of 28 days or 10 scheduled selinexor doses.
|
|---|---|---|---|---|---|
|
Overall Study
STARTED
|
58
|
27
|
81
|
95
|
24
|
|
Overall Study
COMPLETED
|
0
|
0
|
0
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
58
|
27
|
81
|
95
|
24
|
Reasons for withdrawal
| Measure |
Diffuse Large B-cell Lymphoma (DLBCL)
Participants with DLBCL received Selinexor in different Schedules; Schedule 1: \<= 12 milligram per square meter (mg/m\^2) per orally (PO) alternating 3 times per week with twice weekly dosing (1 day between doses); Schedule 2: \> 12 mg/m\^2 PO 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 8: \>=40 mg/m\^2 PO twice weekly (1 day between doses) during Weeks 1 and 2; Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab intravenous (IV) once weekly for Weeks 1-4 during different cycles. Each cycle was of 28 days (Schedule 8: 21 days of cycle) or 10 scheduled selinexor doses.
|
Non-Hodgkin Lymphoma (NHL) Excluding DLBCL
Participants with NHL received Selinexor in different Schedules; Schedule 1: \<= 12 mg/m\^2 PO alternating 3 times per week with twice weekly dosing (1 day between doses); Schedule 2: \> 12 mg/m\^2 PO 3 times weekly for week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs 1 day apart (Schedule 3); Schedule 7: \>=45 mg/m\^2 PO once weekly (6 days between doses) to evaluate vs twice weekly (Schedules 3, 4, 5, and 6); Schedule 8: \>=40 mg/m\^2 PO twice weekly \[1 Day between doses\] during weeks 1 and 2; Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab IV once weekly for Weeks 1-4) during different cycles. Each cycle was of 28 days (Schedule 8: 21 days of cycle) or 10 scheduled selinexor doses.
|
Multiple Myeloma (MM)
Participants with MM received Selinexor in different Schedules; Schedule 1: \<= 12 mg/m\^2 PO alternating 3 times per week with twice weekly dosing (1 Day between doses); Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; 3 doses (36 mg/m\^2 total) in the 1-week run-in period; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 6: \>= 35 mg/m\^2 PO twice weekly with dexamethasone (20 mg twice weekly) on Days of twice weekly Selinexor dosing; Schedule 11: Group A: 40 mg; Group B: 60 mg; Group C: 80 mg twice weekly (Weeks 1, 2, and 3) at 3 fixed dose levels during different cycles. Each cycle was of 28 days or 10 scheduled selinexor doses.
|
Acute Myeloid Leukemia (AML)
Participants with AML received Selinexor in different Schedules; Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3), Schedule 7: \>=45 mg/m\^2 PO once weekly (6 Days between doses) to evaluate vs. twice weekly (Schedules 3, 4, 5, and 6); Schedule 8: \>=40 mg/m\^2 PO twice weekly (1 Day between doses) during Weeks 1 and 2; Schedule 10: \>= 55 mg/m\^2 PO twice weekly PO (Weeks 1 and 2) in participants with AML/18-Day treatment-free interval) during different cycles. Each cycle was of 28 days (for schedule 8: 21-day of cycle) or 10 scheduled selinexor doses.
|
Other Hematological Malignancies (ALL, CML and CLL)
Participants with other hematological malignancies (Acute lymphoblastic leukemia \[ALL\], Chronic myelogenous leukemia \[CML\] and chronic lymphocytic leukemia \[CLL\]) received Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly \[1 day between doses\]; Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 7: \>=45 mg/m\^2 PO once weekly (6 Days between doses) to evaluate vs. twice weekly (Schedules 3, 4, 5, and 6); Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab IV once weekly for Weeks 1-4 during different cycles. Each cycle was of 28 days or 10 scheduled selinexor doses.
|
|---|---|---|---|---|---|
|
Overall Study
Need of treatment not allowed per protocol
|
0
|
0
|
0
|
1
|
0
|
|
Overall Study
Death
|
4
|
2
|
8
|
10
|
3
|
|
Overall Study
Investigator discretion
|
2
|
4
|
4
|
8
|
0
|
|
Overall Study
Other treatments became available
|
1
|
1
|
0
|
0
|
2
|
|
Overall Study
Intercurrent illness
|
1
|
0
|
0
|
3
|
0
|
|
Overall Study
Non-Compliance with study procedures
|
0
|
0
|
1
|
0
|
0
|
|
Overall Study
Consent withdrawn by participant
|
9
|
4
|
24
|
14
|
4
|
|
Overall Study
Disease progression
|
38
|
13
|
37
|
57
|
9
|
|
Overall Study
Incidence or severity of Adverse events
|
3
|
3
|
7
|
2
|
6
|
Baseline Characteristics
Safety Study of the Selective Inhibitor of Nuclear Export (SINE) KPT-330 in Patients With Advanced Hematological Cancer
Baseline characteristics by cohort
| Measure |
Diffuse Large B-cell Lymphoma (DLBCL)
n=58 Participants
Participants with DLBCL received Selinexor in different Schedules; Schedule 1: \<= 12 milligram per square meter (mg/m\^2) per orally (PO) alternating 3 times per week with twice weekly dosing (1 day between doses); Schedule 2: \> 12 mg/m\^2 PO 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 8: \>=40 mg/m\^2 PO twice weekly (1 day between doses) during Weeks 1 and 2; Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab intravenous (IV) once weekly for Weeks 1-4 during different cycles. Each cycle was of 28 days (Schedule 8: 21 days of cycle) or 10 scheduled selinexor doses.
|
Non-Hodgkin Lymphoma (NHL) Excluding DLBCL
n=27 Participants
Participants with NHL received Selinexor in different Schedules; Schedule 1: \<= 12 mg/m\^2 PO alternating 3 times per week with twice weekly dosing (1 day between doses); Schedule 2: \> 12 mg/m\^2 PO 3 times weekly for week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs 1 day apart (Schedule 3); Schedule 7: \>=45 mg/m\^2 PO once weekly (6 days between doses) to evaluate vs twice weekly (Schedules 3, 4, 5, and 6); Schedule 8: \>=40 mg/m\^2 PO twice weekly \[1 Day between doses\] during weeks 1 and 2; Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab IV once weekly for Weeks 1-4) during different cycles. Each cycle was of 28 days (Schedule 8: 21 days of cycle) or 10 scheduled selinexor doses.
|
Multiple Myeloma (MM)
n=81 Participants
Participants with MM received Selinexor in different Schedules; Schedule 1: \<= 12 mg/m\^2 PO alternating 3 times per week with twice weekly dosing (1 Day between doses); Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; 3 doses (36 mg/m\^2 total) in the 1-week run-in period; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 6: \>= 35 mg/m\^2 PO twice weekly with dexamethasone (20 mg twice weekly) on Days of twice weekly Selinexor dosing; Schedule 11: Group A: 40 mg; Group B: 60 mg; Group C: 80 mg twice weekly (Weeks 1, 2, and 3) at 3 fixed dose levels during different cycles. Each cycle was of 28 days or 10 scheduled selinexor doses.
|
Acute Myeloid Leukemia (AML)
n=95 Participants
Participants with AML received Selinexor in different Schedules; Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3), Schedule 7: \>=45 mg/m\^2 PO once weekly (6 Days between doses) to evaluate vs. twice weekly (Schedules 3, 4, 5, and 6); Schedule 8: \>=40 mg/m\^2 PO twice weekly (1 Day between doses) during Weeks 1 and 2; Schedule 10: \>= 55 mg/m\^2 PO twice weekly PO (Weeks 1 and 2) in participants with AML/18-Day treatment-free interval) during different cycles. Each cycle was of 28 days (for schedule 8: 21-day of cycle) or 10 scheduled selinexor doses.
|
Other Hematological Malignancies (ALL, CML and CLL)
n=24 Participants
Participants with other hematological malignancies (Acute lymphoblastic leukemia \[ALL\], Chronic myelogenous leukemia \[CML\] and chronic lymphocytic leukemia \[CLL\]) received Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly \[1 day between doses\]; Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 7: \>=45 mg/m\^2 PO once weekly (6 Days between doses) to evaluate vs. twice weekly (Schedules 3, 4, 5, and 6); Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab IV once weekly for Weeks 1-4 during different cycles. Each cycle was of 28 days or 10 scheduled selinexor doses.
|
Total
n=285 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Continuous
|
57.8 years
STANDARD_DEVIATION 14.00 • n=93 Participants
|
58.0 years
STANDARD_DEVIATION 15.90 • n=4 Participants
|
62.1 years
STANDARD_DEVIATION 8.76 • n=27 Participants
|
65.6 years
STANDARD_DEVIATION 15.33 • n=483 Participants
|
60.9 years
STANDARD_DEVIATION 15.23 • n=36 Participants
|
61.9 years
STANDARD_DEVIATION 13.79 • n=10 Participants
|
|
Sex: Female, Male
Female
|
28 Participants
n=93 Participants
|
9 Participants
n=4 Participants
|
38 Participants
n=27 Participants
|
40 Participants
n=483 Participants
|
8 Participants
n=36 Participants
|
123 Participants
n=10 Participants
|
|
Sex: Female, Male
Male
|
30 Participants
n=93 Participants
|
18 Participants
n=4 Participants
|
43 Participants
n=27 Participants
|
55 Participants
n=483 Participants
|
16 Participants
n=36 Participants
|
162 Participants
n=10 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
4 Participants
n=27 Participants
|
2 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
9 Participants
n=10 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
52 Participants
n=93 Participants
|
23 Participants
n=4 Participants
|
72 Participants
n=27 Participants
|
88 Participants
n=483 Participants
|
23 Participants
n=36 Participants
|
258 Participants
n=10 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
4 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
5 Participants
n=27 Participants
|
5 Participants
n=483 Participants
|
1 Participants
n=36 Participants
|
18 Participants
n=10 Participants
|
|
Race/Ethnicity, Customized
White
|
52 Participants
n=93 Participants
|
20 Participants
n=4 Participants
|
65 Participants
n=27 Participants
|
88 Participants
n=483 Participants
|
23 Participants
n=36 Participants
|
248 Participants
n=10 Participants
|
|
Race/Ethnicity, Customized
Black
|
2 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
11 Participants
n=27 Participants
|
5 Participants
n=483 Participants
|
1 Participants
n=36 Participants
|
22 Participants
n=10 Participants
|
|
Race/Ethnicity, Customized
Asian
|
0 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
4 Participants
n=27 Participants
|
1 Participants
n=483 Participants
|
1 Participants
n=36 Participants
|
7 Participants
n=10 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
0 Participants
n=10 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaskan Native
|
0 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
1 Participants
n=10 Participants
|
|
Race/Ethnicity, Customized
Other
|
0 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
3 Participants
n=10 Participants
|
|
Race/Ethnicity, Customized
Unknown/Not Reported
|
4 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
1 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
5 Participants
n=10 Participants
|
PRIMARY outcome
Timeframe: From first dose of study drug administration to end of treatment (up to 27 months)Population: Safety population consisted of all participants who received at least 1 dose of selinexor.
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product during the course of a study and which does not necessarily have to have a causal relationship with this treatment. An Serious adverse event (SAE) was an AE resulting in any of the following outcomes: death; life-threatening event; required or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly. TEAEs are any untoward medical incidence in a participant during administered study treatment, whether or not these events were related to study treatment.
Outcome measures
| Measure |
Diffuse Large B-cell Lymphoma (DLBCL)
n=58 Participants
Participants with DLBCL received Selinexor in different Schedules; Schedule 1: \<= 12 milligram per square meter (mg/m\^2) per orally (PO) alternating 3 times per week with twice weekly dosing (1 day between doses); Schedule 2: \> 12 mg/m\^2 PO 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 8: \>=40 mg/m\^2 PO twice weekly (1 day between doses) during Weeks 1 and 2; Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab intravenous (IV) once weekly for Weeks 1-4 during different cycles. Each cycle was of 28 days (Schedule 8: 21 days of cycle) or 10 scheduled selinexor doses.
|
Non-Hodgkin Lymphoma (NHL) Excluding DLBCL
n=27 Participants
Participants with NHL received Selinexor in different Schedules; Schedule 1: \<= 12 mg/m\^2 PO alternating 3 times per week with twice weekly dosing (1 day between doses); Schedule 2: \> 12 mg/m\^2 PO 3 times weekly for week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs 1 day apart (Schedule 3); Schedule 7: \>=45 mg/m\^2 PO once weekly (6 days between doses) to evaluate vs twice weekly (Schedules 3, 4, 5, and 6); Schedule 8: \>=40 mg/m\^2 PO twice weekly \[1 Day between doses\] during weeks 1 and 2; Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab IV once weekly for Weeks 1-4) during different cycles. Each cycle was of 28 days (Schedule 8: 21 days of cycle) or 10 scheduled selinexor doses.
|
Multiple Myeloma (MM)
n=81 Participants
Participants with MM received Selinexor in different Schedules; Schedule 1: \<= 12 mg/m\^2 PO alternating 3 times per week with twice weekly dosing (1 Day between doses); Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; 3 doses (36 mg/m\^2 total) in the 1-week run-in period; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 6: \>= 35 mg/m\^2 PO twice weekly with dexamethasone (20 mg twice weekly) on Days of twice weekly Selinexor dosing; Schedule 11: Group A: 40 mg; Group B: 60 mg; Group C: 80 mg twice weekly (Weeks 1, 2, and 3) at 3 fixed dose levels during different cycles. Each cycle was of 28 days or 10 scheduled selinexor doses.
|
Acute Myeloid Leukemia (AML)
n=95 Participants
Participants with AML received Selinexor in different Schedules; Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3), Schedule 7: \>=45 mg/m\^2 PO once weekly (6 Days between doses) to evaluate vs. twice weekly (Schedules 3, 4, 5, and 6); Schedule 8: \>=40 mg/m\^2 PO twice weekly (1 Day between doses) during Weeks 1 and 2; Schedule 10: \>= 55 mg/m\^2 PO twice weekly PO (Weeks 1 and 2) in participants with AML/18-Day treatment-free interval) during different cycles. Each cycle was of 28 days (for schedule 8: 21-day of cycle) or 10 scheduled selinexor doses.
|
Other Hematological Malignancies (ALL, CML and CLL)
n=24 Participants
Participants with other hematological malignancies (Acute lymphoblastic leukemia \[ALL\], Chronic myelogenous leukemia \[CML\] and chronic lymphocytic leukemia \[CLL\]) received Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly \[1 day between doses\]; Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 7: \>=45 mg/m\^2 PO once weekly (6 Days between doses) to evaluate vs. twice weekly (Schedules 3, 4, 5, and 6); Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab IV once weekly for Weeks 1-4 during different cycles. Each cycle was of 28 days or 10 scheduled selinexor doses.
|
Selinexor (30 mg/m^2)
Participants received selinexor dose of 30 mg/m\^2 orally at Cycle 1, on Day 1, 3, 4, 8, 10, 15 and 17 in schedule 3, 5 and 9.
|
Selinexor (35 mg/m^2)
Participants received selinexor dose of 35 mg/m\^2 orally at Cycle 1, on Day 1 and 3 in schedule 6.
|
Selinexor (40 mg/m^2)
Participants received selinexor dose of 40 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, 17 followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 8 and 11.
|
Selinexor (46 mg/m^2)
Participants received selinexor dose of 46 mg/m\^2 orally at Cycle 1, on Day 1 once-weekly in schedule 7.
|
Selinexor (55 mg/m^2)
Participants received selinexor dose of 55 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, and 10, followed by an 18-day treatment-free interval (Days 11 through 28) in schedule 10.
|
Selinexor (60 mg/m^2)
Participants received selinexor dose of 60 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, and 17, followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 11.
|
Selinexor (70 mg/m^2)
Participants received selinexor dose of 70 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, and 17, followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 11.
|
Selinexor (80 mg/m^2)
Participants received selinexor dose of 80 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, and 17, followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 11.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
At Least One TEAE
|
58 Participants
|
27 Participants
|
81 Participants
|
95 Participants
|
24 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
At Least One Serious TEAE
|
33 Participants
|
7 Participants
|
52 Participants
|
73 Participants
|
13 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: From first dose of study drug administration to end of treatment (up to 27 months)Population: Efficacy analysis set included all participants who had either completed 1 cycle of treatment or discontinued treatment prior to completing the first cycle due to documented progressive disease (PD), death related to disease, or treatment-related toxicity. Here, data was not planned and analyzed based on individual specific disease, hence overall data was analyzed for this outcome measure.
Recommended Phase 2 dose was determined by maximum tolerated dose (MTD). MTD was defined as the next lower dose level below the one in which \> 1 of 3 participants or ≥ 2 of 6 participants experienced dose-limiting toxicity (DLT), provided that that dose level is ≤25% lower than the highest dose tested. If the projected MTD was \>25% lower than the highest dose tested, then an additional cohort of ≥3 participants were added at a dose that was intermediate between the intolerable dose and the next lower dose.
Outcome measures
| Measure |
Diffuse Large B-cell Lymphoma (DLBCL)
n=285 Participants
Participants with DLBCL received Selinexor in different Schedules; Schedule 1: \<= 12 milligram per square meter (mg/m\^2) per orally (PO) alternating 3 times per week with twice weekly dosing (1 day between doses); Schedule 2: \> 12 mg/m\^2 PO 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 8: \>=40 mg/m\^2 PO twice weekly (1 day between doses) during Weeks 1 and 2; Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab intravenous (IV) once weekly for Weeks 1-4 during different cycles. Each cycle was of 28 days (Schedule 8: 21 days of cycle) or 10 scheduled selinexor doses.
|
Non-Hodgkin Lymphoma (NHL) Excluding DLBCL
Participants with NHL received Selinexor in different Schedules; Schedule 1: \<= 12 mg/m\^2 PO alternating 3 times per week with twice weekly dosing (1 day between doses); Schedule 2: \> 12 mg/m\^2 PO 3 times weekly for week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs 1 day apart (Schedule 3); Schedule 7: \>=45 mg/m\^2 PO once weekly (6 days between doses) to evaluate vs twice weekly (Schedules 3, 4, 5, and 6); Schedule 8: \>=40 mg/m\^2 PO twice weekly \[1 Day between doses\] during weeks 1 and 2; Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab IV once weekly for Weeks 1-4) during different cycles. Each cycle was of 28 days (Schedule 8: 21 days of cycle) or 10 scheduled selinexor doses.
|
Multiple Myeloma (MM)
Participants with MM received Selinexor in different Schedules; Schedule 1: \<= 12 mg/m\^2 PO alternating 3 times per week with twice weekly dosing (1 Day between doses); Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; 3 doses (36 mg/m\^2 total) in the 1-week run-in period; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 6: \>= 35 mg/m\^2 PO twice weekly with dexamethasone (20 mg twice weekly) on Days of twice weekly Selinexor dosing; Schedule 11: Group A: 40 mg; Group B: 60 mg; Group C: 80 mg twice weekly (Weeks 1, 2, and 3) at 3 fixed dose levels during different cycles. Each cycle was of 28 days or 10 scheduled selinexor doses.
|
Acute Myeloid Leukemia (AML)
Participants with AML received Selinexor in different Schedules; Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3), Schedule 7: \>=45 mg/m\^2 PO once weekly (6 Days between doses) to evaluate vs. twice weekly (Schedules 3, 4, 5, and 6); Schedule 8: \>=40 mg/m\^2 PO twice weekly (1 Day between doses) during Weeks 1 and 2; Schedule 10: \>= 55 mg/m\^2 PO twice weekly PO (Weeks 1 and 2) in participants with AML/18-Day treatment-free interval) during different cycles. Each cycle was of 28 days (for schedule 8: 21-day of cycle) or 10 scheduled selinexor doses.
|
Other Hematological Malignancies (ALL, CML and CLL)
Participants with other hematological malignancies (Acute lymphoblastic leukemia \[ALL\], Chronic myelogenous leukemia \[CML\] and chronic lymphocytic leukemia \[CLL\]) received Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly \[1 day between doses\]; Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 7: \>=45 mg/m\^2 PO once weekly (6 Days between doses) to evaluate vs. twice weekly (Schedules 3, 4, 5, and 6); Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab IV once weekly for Weeks 1-4 during different cycles. Each cycle was of 28 days or 10 scheduled selinexor doses.
|
Selinexor (30 mg/m^2)
Participants received selinexor dose of 30 mg/m\^2 orally at Cycle 1, on Day 1, 3, 4, 8, 10, 15 and 17 in schedule 3, 5 and 9.
|
Selinexor (35 mg/m^2)
Participants received selinexor dose of 35 mg/m\^2 orally at Cycle 1, on Day 1 and 3 in schedule 6.
|
Selinexor (40 mg/m^2)
Participants received selinexor dose of 40 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, 17 followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 8 and 11.
|
Selinexor (46 mg/m^2)
Participants received selinexor dose of 46 mg/m\^2 orally at Cycle 1, on Day 1 once-weekly in schedule 7.
|
Selinexor (55 mg/m^2)
Participants received selinexor dose of 55 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, and 10, followed by an 18-day treatment-free interval (Days 11 through 28) in schedule 10.
|
Selinexor (60 mg/m^2)
Participants received selinexor dose of 60 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, and 17, followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 11.
|
Selinexor (70 mg/m^2)
Participants received selinexor dose of 70 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, and 17, followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 11.
|
Selinexor (80 mg/m^2)
Participants received selinexor dose of 80 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, and 17, followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 11.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Recommended Phase 2 Dose (RP2D) of Selinexor
|
35 milligram per square meter (mg/m^2)
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 2, 4, 8, 24 and 48 hours post-dose on Day 1, 8 of Cycle 1 and Days 15, 16 or 17 of Cycle 2Population: Pharmacokinetic (PK) analysis was defined as all participants who received active drug, selinexor, without the co-administration of another chemotherapeutic (i.e., rituximab), and for whom the PK profile for cycle 1 day1 (C1D1) could be adequately characterized. Here 'Overall Number of Participants Analyzed' signifies number of participants analyzed for this outcome measure.
Cmax was defined as the maximum observed concentration, taken directly from the plasma concentration.
Outcome measures
| Measure |
Diffuse Large B-cell Lymphoma (DLBCL)
n=2 Participants
Participants with DLBCL received Selinexor in different Schedules; Schedule 1: \<= 12 milligram per square meter (mg/m\^2) per orally (PO) alternating 3 times per week with twice weekly dosing (1 day between doses); Schedule 2: \> 12 mg/m\^2 PO 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 8: \>=40 mg/m\^2 PO twice weekly (1 day between doses) during Weeks 1 and 2; Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab intravenous (IV) once weekly for Weeks 1-4 during different cycles. Each cycle was of 28 days (Schedule 8: 21 days of cycle) or 10 scheduled selinexor doses.
|
Non-Hodgkin Lymphoma (NHL) Excluding DLBCL
n=3 Participants
Participants with NHL received Selinexor in different Schedules; Schedule 1: \<= 12 mg/m\^2 PO alternating 3 times per week with twice weekly dosing (1 day between doses); Schedule 2: \> 12 mg/m\^2 PO 3 times weekly for week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs 1 day apart (Schedule 3); Schedule 7: \>=45 mg/m\^2 PO once weekly (6 days between doses) to evaluate vs twice weekly (Schedules 3, 4, 5, and 6); Schedule 8: \>=40 mg/m\^2 PO twice weekly \[1 Day between doses\] during weeks 1 and 2; Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab IV once weekly for Weeks 1-4) during different cycles. Each cycle was of 28 days (Schedule 8: 21 days of cycle) or 10 scheduled selinexor doses.
|
Multiple Myeloma (MM)
n=6 Participants
Participants with MM received Selinexor in different Schedules; Schedule 1: \<= 12 mg/m\^2 PO alternating 3 times per week with twice weekly dosing (1 Day between doses); Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; 3 doses (36 mg/m\^2 total) in the 1-week run-in period; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 6: \>= 35 mg/m\^2 PO twice weekly with dexamethasone (20 mg twice weekly) on Days of twice weekly Selinexor dosing; Schedule 11: Group A: 40 mg; Group B: 60 mg; Group C: 80 mg twice weekly (Weeks 1, 2, and 3) at 3 fixed dose levels during different cycles. Each cycle was of 28 days or 10 scheduled selinexor doses.
|
Acute Myeloid Leukemia (AML)
n=13 Participants
Participants with AML received Selinexor in different Schedules; Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3), Schedule 7: \>=45 mg/m\^2 PO once weekly (6 Days between doses) to evaluate vs. twice weekly (Schedules 3, 4, 5, and 6); Schedule 8: \>=40 mg/m\^2 PO twice weekly (1 Day between doses) during Weeks 1 and 2; Schedule 10: \>= 55 mg/m\^2 PO twice weekly PO (Weeks 1 and 2) in participants with AML/18-Day treatment-free interval) during different cycles. Each cycle was of 28 days (for schedule 8: 21-day of cycle) or 10 scheduled selinexor doses.
|
Other Hematological Malignancies (ALL, CML and CLL)
n=18 Participants
Participants with other hematological malignancies (Acute lymphoblastic leukemia \[ALL\], Chronic myelogenous leukemia \[CML\] and chronic lymphocytic leukemia \[CLL\]) received Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly \[1 day between doses\]; Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 7: \>=45 mg/m\^2 PO once weekly (6 Days between doses) to evaluate vs. twice weekly (Schedules 3, 4, 5, and 6); Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab IV once weekly for Weeks 1-4 during different cycles. Each cycle was of 28 days or 10 scheduled selinexor doses.
|
Selinexor (30 mg/m^2)
n=21 Participants
Participants received selinexor dose of 30 mg/m\^2 orally at Cycle 1, on Day 1, 3, 4, 8, 10, 15 and 17 in schedule 3, 5 and 9.
|
Selinexor (35 mg/m^2)
n=13 Participants
Participants received selinexor dose of 35 mg/m\^2 orally at Cycle 1, on Day 1 and 3 in schedule 6.
|
Selinexor (40 mg/m^2)
n=8 Participants
Participants received selinexor dose of 40 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, 17 followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 8 and 11.
|
Selinexor (46 mg/m^2)
n=9 Participants
Participants received selinexor dose of 46 mg/m\^2 orally at Cycle 1, on Day 1 once-weekly in schedule 7.
|
Selinexor (55 mg/m^2)
n=8 Participants
Participants received selinexor dose of 55 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, and 10, followed by an 18-day treatment-free interval (Days 11 through 28) in schedule 10.
|
Selinexor (60 mg/m^2)
n=4 Participants
Participants received selinexor dose of 60 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, and 17, followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 11.
|
Selinexor (70 mg/m^2)
n=8 Participants
Participants received selinexor dose of 70 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, and 17, followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 11.
|
Selinexor (80 mg/m^2)
n=5 Participants
Participants received selinexor dose of 80 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, and 17, followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 11.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of Selinexor
|
49.0 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation NA
Geometric coefficient of variation (CV) was not calculated as data were available for only two participants.
|
50.0 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 61.1
|
149 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 37.6
|
205 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 46.8
|
262 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 37.5
|
387 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 37.1
|
407 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 44.4
|
416 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 36.6
|
670 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 18.5
|
583 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 41.4
|
668 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 33.2
|
800 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 32.4
|
1068 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 49.3
|
SECONDARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 2, 4, 8, 24 and 48 hours post-dose on Day 1, 8 of Cycle 1 and Days 15, 16 or 17 of Cycle 2Population: PK analysis was defined as all participants who received active drug, selinexor, without the co-administration of another chemotherapeutic (i.e., rituximab), and for whom the PK profile for C1D1 could be adequately characterized. Here 'Overall Number of Participants Analyzed' signifies number of participants analyzed for this outcome measure.
Tmax was defined as time of first observation of Cmax, taken directly from the plasma concentration data.
Outcome measures
| Measure |
Diffuse Large B-cell Lymphoma (DLBCL)
n=2 Participants
Participants with DLBCL received Selinexor in different Schedules; Schedule 1: \<= 12 milligram per square meter (mg/m\^2) per orally (PO) alternating 3 times per week with twice weekly dosing (1 day between doses); Schedule 2: \> 12 mg/m\^2 PO 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 8: \>=40 mg/m\^2 PO twice weekly (1 day between doses) during Weeks 1 and 2; Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab intravenous (IV) once weekly for Weeks 1-4 during different cycles. Each cycle was of 28 days (Schedule 8: 21 days of cycle) or 10 scheduled selinexor doses.
|
Non-Hodgkin Lymphoma (NHL) Excluding DLBCL
n=3 Participants
Participants with NHL received Selinexor in different Schedules; Schedule 1: \<= 12 mg/m\^2 PO alternating 3 times per week with twice weekly dosing (1 day between doses); Schedule 2: \> 12 mg/m\^2 PO 3 times weekly for week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs 1 day apart (Schedule 3); Schedule 7: \>=45 mg/m\^2 PO once weekly (6 days between doses) to evaluate vs twice weekly (Schedules 3, 4, 5, and 6); Schedule 8: \>=40 mg/m\^2 PO twice weekly \[1 Day between doses\] during weeks 1 and 2; Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab IV once weekly for Weeks 1-4) during different cycles. Each cycle was of 28 days (Schedule 8: 21 days of cycle) or 10 scheduled selinexor doses.
|
Multiple Myeloma (MM)
n=6 Participants
Participants with MM received Selinexor in different Schedules; Schedule 1: \<= 12 mg/m\^2 PO alternating 3 times per week with twice weekly dosing (1 Day between doses); Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; 3 doses (36 mg/m\^2 total) in the 1-week run-in period; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 6: \>= 35 mg/m\^2 PO twice weekly with dexamethasone (20 mg twice weekly) on Days of twice weekly Selinexor dosing; Schedule 11: Group A: 40 mg; Group B: 60 mg; Group C: 80 mg twice weekly (Weeks 1, 2, and 3) at 3 fixed dose levels during different cycles. Each cycle was of 28 days or 10 scheduled selinexor doses.
|
Acute Myeloid Leukemia (AML)
n=13 Participants
Participants with AML received Selinexor in different Schedules; Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3), Schedule 7: \>=45 mg/m\^2 PO once weekly (6 Days between doses) to evaluate vs. twice weekly (Schedules 3, 4, 5, and 6); Schedule 8: \>=40 mg/m\^2 PO twice weekly (1 Day between doses) during Weeks 1 and 2; Schedule 10: \>= 55 mg/m\^2 PO twice weekly PO (Weeks 1 and 2) in participants with AML/18-Day treatment-free interval) during different cycles. Each cycle was of 28 days (for schedule 8: 21-day of cycle) or 10 scheduled selinexor doses.
|
Other Hematological Malignancies (ALL, CML and CLL)
n=18 Participants
Participants with other hematological malignancies (Acute lymphoblastic leukemia \[ALL\], Chronic myelogenous leukemia \[CML\] and chronic lymphocytic leukemia \[CLL\]) received Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly \[1 day between doses\]; Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 7: \>=45 mg/m\^2 PO once weekly (6 Days between doses) to evaluate vs. twice weekly (Schedules 3, 4, 5, and 6); Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab IV once weekly for Weeks 1-4 during different cycles. Each cycle was of 28 days or 10 scheduled selinexor doses.
|
Selinexor (30 mg/m^2)
n=21 Participants
Participants received selinexor dose of 30 mg/m\^2 orally at Cycle 1, on Day 1, 3, 4, 8, 10, 15 and 17 in schedule 3, 5 and 9.
|
Selinexor (35 mg/m^2)
n=13 Participants
Participants received selinexor dose of 35 mg/m\^2 orally at Cycle 1, on Day 1 and 3 in schedule 6.
|
Selinexor (40 mg/m^2)
n=8 Participants
Participants received selinexor dose of 40 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, 17 followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 8 and 11.
|
Selinexor (46 mg/m^2)
n=9 Participants
Participants received selinexor dose of 46 mg/m\^2 orally at Cycle 1, on Day 1 once-weekly in schedule 7.
|
Selinexor (55 mg/m^2)
n=8 Participants
Participants received selinexor dose of 55 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, and 10, followed by an 18-day treatment-free interval (Days 11 through 28) in schedule 10.
|
Selinexor (60 mg/m^2)
n=4 Participants
Participants received selinexor dose of 60 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, and 17, followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 11.
|
Selinexor (70 mg/m^2)
n=8 Participants
Participants received selinexor dose of 70 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, and 17, followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 11.
|
Selinexor (80 mg/m^2)
n=5 Participants
Participants received selinexor dose of 80 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, and 17, followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 11.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Time to Maximum Observed Concentration (Tmax) of Selinexor
|
NA hour
Interval 2.1 to 2.2
Median value was not calculated due to insufficient PK samples required for calculation.
|
4.0 hour
Interval 2.1 to 7.7
|
3.0 hour
Interval 1.1 to 4.2
|
2.08 hour
Interval 0.92 to 8.5
|
2.0 hour
Interval 1.0 to 7.8
|
2.0 hour
Interval 0.72 to 4.4
|
2.0 hour
Interval 0.92 to 4.1
|
4.0 hour
Interval 2.0 to 7.5
|
2.0 hour
Interval 0.5 to 4.2
|
2.9 hour
Interval 1.0 to 8.0
|
1.9 hour
Interval 1.8 to 2.0
|
2.0 hour
Interval 1.0 to 4.0
|
2.0 hour
Interval 0.5 to 4.0
|
SECONDARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 2, 4, 8, 24 and 48 hours post-dose on Day 1, 8 of Cycle 1 and Days 15, 16 or 17 of Cycle 2Population: PK analysis was defined as all participants who received active drug, selinexor, without the co-administration of another chemotherapeutic (i.e., rituximab), and for whom the PK profile for C1D1 could be adequately characterized. Here 'Overall Number of Participants Analyzed' signifies number of participants analyzed for this outcome measure.
Cavg0-24h was defined as average concentration from time 0 to 24 hours.
Outcome measures
| Measure |
Diffuse Large B-cell Lymphoma (DLBCL)
n=2 Participants
Participants with DLBCL received Selinexor in different Schedules; Schedule 1: \<= 12 milligram per square meter (mg/m\^2) per orally (PO) alternating 3 times per week with twice weekly dosing (1 day between doses); Schedule 2: \> 12 mg/m\^2 PO 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 8: \>=40 mg/m\^2 PO twice weekly (1 day between doses) during Weeks 1 and 2; Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab intravenous (IV) once weekly for Weeks 1-4 during different cycles. Each cycle was of 28 days (Schedule 8: 21 days of cycle) or 10 scheduled selinexor doses.
|
Non-Hodgkin Lymphoma (NHL) Excluding DLBCL
n=3 Participants
Participants with NHL received Selinexor in different Schedules; Schedule 1: \<= 12 mg/m\^2 PO alternating 3 times per week with twice weekly dosing (1 day between doses); Schedule 2: \> 12 mg/m\^2 PO 3 times weekly for week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs 1 day apart (Schedule 3); Schedule 7: \>=45 mg/m\^2 PO once weekly (6 days between doses) to evaluate vs twice weekly (Schedules 3, 4, 5, and 6); Schedule 8: \>=40 mg/m\^2 PO twice weekly \[1 Day between doses\] during weeks 1 and 2; Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab IV once weekly for Weeks 1-4) during different cycles. Each cycle was of 28 days (Schedule 8: 21 days of cycle) or 10 scheduled selinexor doses.
|
Multiple Myeloma (MM)
n=6 Participants
Participants with MM received Selinexor in different Schedules; Schedule 1: \<= 12 mg/m\^2 PO alternating 3 times per week with twice weekly dosing (1 Day between doses); Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; 3 doses (36 mg/m\^2 total) in the 1-week run-in period; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 6: \>= 35 mg/m\^2 PO twice weekly with dexamethasone (20 mg twice weekly) on Days of twice weekly Selinexor dosing; Schedule 11: Group A: 40 mg; Group B: 60 mg; Group C: 80 mg twice weekly (Weeks 1, 2, and 3) at 3 fixed dose levels during different cycles. Each cycle was of 28 days or 10 scheduled selinexor doses.
|
Acute Myeloid Leukemia (AML)
n=12 Participants
Participants with AML received Selinexor in different Schedules; Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3), Schedule 7: \>=45 mg/m\^2 PO once weekly (6 Days between doses) to evaluate vs. twice weekly (Schedules 3, 4, 5, and 6); Schedule 8: \>=40 mg/m\^2 PO twice weekly (1 Day between doses) during Weeks 1 and 2; Schedule 10: \>= 55 mg/m\^2 PO twice weekly PO (Weeks 1 and 2) in participants with AML/18-Day treatment-free interval) during different cycles. Each cycle was of 28 days (for schedule 8: 21-day of cycle) or 10 scheduled selinexor doses.
|
Other Hematological Malignancies (ALL, CML and CLL)
n=17 Participants
Participants with other hematological malignancies (Acute lymphoblastic leukemia \[ALL\], Chronic myelogenous leukemia \[CML\] and chronic lymphocytic leukemia \[CLL\]) received Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly \[1 day between doses\]; Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 7: \>=45 mg/m\^2 PO once weekly (6 Days between doses) to evaluate vs. twice weekly (Schedules 3, 4, 5, and 6); Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab IV once weekly for Weeks 1-4 during different cycles. Each cycle was of 28 days or 10 scheduled selinexor doses.
|
Selinexor (30 mg/m^2)
n=19 Participants
Participants received selinexor dose of 30 mg/m\^2 orally at Cycle 1, on Day 1, 3, 4, 8, 10, 15 and 17 in schedule 3, 5 and 9.
|
Selinexor (35 mg/m^2)
n=13 Participants
Participants received selinexor dose of 35 mg/m\^2 orally at Cycle 1, on Day 1 and 3 in schedule 6.
|
Selinexor (40 mg/m^2)
n=8 Participants
Participants received selinexor dose of 40 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, 17 followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 8 and 11.
|
Selinexor (46 mg/m^2)
n=9 Participants
Participants received selinexor dose of 46 mg/m\^2 orally at Cycle 1, on Day 1 once-weekly in schedule 7.
|
Selinexor (55 mg/m^2)
n=6 Participants
Participants received selinexor dose of 55 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, and 10, followed by an 18-day treatment-free interval (Days 11 through 28) in schedule 10.
|
Selinexor (60 mg/m^2)
n=3 Participants
Participants received selinexor dose of 60 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, and 17, followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 11.
|
Selinexor (70 mg/m^2)
n=4 Participants
Participants received selinexor dose of 70 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, and 17, followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 11.
|
Selinexor (80 mg/m^2)
n=1 Participants
Participants received selinexor dose of 80 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, and 17, followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 11.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Average Concentration From Time 0 to 24 Hours (Cavg0-24h) of Selinexor
|
17.0 ng/mL
Geometric Coefficient of Variation NA
Geometric CV was not calculated as data were available for only two participants.
|
20.3 ng/mL
Geometric Coefficient of Variation 94.8
|
61.8 ng/mL
Geometric Coefficient of Variation 39.9
|
79.0 ng/mL
Geometric Coefficient of Variation 61.8
|
108 ng/mL
Geometric Coefficient of Variation 46.8
|
160 ng/mL
Geometric Coefficient of Variation 38.0
|
168 ng/mL
Geometric Coefficient of Variation 54.0
|
163 ng/mL
Geometric Coefficient of Variation 29.2
|
297 ng/mL
Geometric Coefficient of Variation 26.3
|
208 ng/mL
Geometric Coefficient of Variation 19.1
|
337 ng/mL
Geometric Coefficient of Variation 4.2
|
353 ng/mL
Geometric Coefficient of Variation 26.2
|
NA ng/mL
Geometric Coefficient of Variation NA
Geometric mean and CV were not calculated as data were available for only one participant.
|
SECONDARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 2, 4, 8, 24 and 48 hours post-dose on Day 1, 8 of Cycle 1 and Days 15, 16 or 17 of Cycle 2Population: PK analysis was defined as all participants who received active drug, selinexor, without the co-administration of another chemotherapeutic (i.e., rituximab), and for whom the PK profile for C1D1 could be adequately characterized. Here 'Overall Number of Participants Analyzed' signifies number of participants analyzed for this outcome measure.
AUC0-t was defined as area under the concentration-time curve from time zero to the last non-zero concentration.
Outcome measures
| Measure |
Diffuse Large B-cell Lymphoma (DLBCL)
n=2 Participants
Participants with DLBCL received Selinexor in different Schedules; Schedule 1: \<= 12 milligram per square meter (mg/m\^2) per orally (PO) alternating 3 times per week with twice weekly dosing (1 day between doses); Schedule 2: \> 12 mg/m\^2 PO 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 8: \>=40 mg/m\^2 PO twice weekly (1 day between doses) during Weeks 1 and 2; Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab intravenous (IV) once weekly for Weeks 1-4 during different cycles. Each cycle was of 28 days (Schedule 8: 21 days of cycle) or 10 scheduled selinexor doses.
|
Non-Hodgkin Lymphoma (NHL) Excluding DLBCL
n=3 Participants
Participants with NHL received Selinexor in different Schedules; Schedule 1: \<= 12 mg/m\^2 PO alternating 3 times per week with twice weekly dosing (1 day between doses); Schedule 2: \> 12 mg/m\^2 PO 3 times weekly for week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs 1 day apart (Schedule 3); Schedule 7: \>=45 mg/m\^2 PO once weekly (6 days between doses) to evaluate vs twice weekly (Schedules 3, 4, 5, and 6); Schedule 8: \>=40 mg/m\^2 PO twice weekly \[1 Day between doses\] during weeks 1 and 2; Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab IV once weekly for Weeks 1-4) during different cycles. Each cycle was of 28 days (Schedule 8: 21 days of cycle) or 10 scheduled selinexor doses.
|
Multiple Myeloma (MM)
n=6 Participants
Participants with MM received Selinexor in different Schedules; Schedule 1: \<= 12 mg/m\^2 PO alternating 3 times per week with twice weekly dosing (1 Day between doses); Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; 3 doses (36 mg/m\^2 total) in the 1-week run-in period; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 6: \>= 35 mg/m\^2 PO twice weekly with dexamethasone (20 mg twice weekly) on Days of twice weekly Selinexor dosing; Schedule 11: Group A: 40 mg; Group B: 60 mg; Group C: 80 mg twice weekly (Weeks 1, 2, and 3) at 3 fixed dose levels during different cycles. Each cycle was of 28 days or 10 scheduled selinexor doses.
|
Acute Myeloid Leukemia (AML)
n=13 Participants
Participants with AML received Selinexor in different Schedules; Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3), Schedule 7: \>=45 mg/m\^2 PO once weekly (6 Days between doses) to evaluate vs. twice weekly (Schedules 3, 4, 5, and 6); Schedule 8: \>=40 mg/m\^2 PO twice weekly (1 Day between doses) during Weeks 1 and 2; Schedule 10: \>= 55 mg/m\^2 PO twice weekly PO (Weeks 1 and 2) in participants with AML/18-Day treatment-free interval) during different cycles. Each cycle was of 28 days (for schedule 8: 21-day of cycle) or 10 scheduled selinexor doses.
|
Other Hematological Malignancies (ALL, CML and CLL)
n=18 Participants
Participants with other hematological malignancies (Acute lymphoblastic leukemia \[ALL\], Chronic myelogenous leukemia \[CML\] and chronic lymphocytic leukemia \[CLL\]) received Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly \[1 day between doses\]; Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 7: \>=45 mg/m\^2 PO once weekly (6 Days between doses) to evaluate vs. twice weekly (Schedules 3, 4, 5, and 6); Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab IV once weekly for Weeks 1-4 during different cycles. Each cycle was of 28 days or 10 scheduled selinexor doses.
|
Selinexor (30 mg/m^2)
n=21 Participants
Participants received selinexor dose of 30 mg/m\^2 orally at Cycle 1, on Day 1, 3, 4, 8, 10, 15 and 17 in schedule 3, 5 and 9.
|
Selinexor (35 mg/m^2)
n=13 Participants
Participants received selinexor dose of 35 mg/m\^2 orally at Cycle 1, on Day 1 and 3 in schedule 6.
|
Selinexor (40 mg/m^2)
n=8 Participants
Participants received selinexor dose of 40 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, 17 followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 8 and 11.
|
Selinexor (46 mg/m^2)
n=9 Participants
Participants received selinexor dose of 46 mg/m\^2 orally at Cycle 1, on Day 1 once-weekly in schedule 7.
|
Selinexor (55 mg/m^2)
n=8 Participants
Participants received selinexor dose of 55 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, and 10, followed by an 18-day treatment-free interval (Days 11 through 28) in schedule 10.
|
Selinexor (60 mg/m^2)
n=4 Participants
Participants received selinexor dose of 60 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, and 17, followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 11.
|
Selinexor (70 mg/m^2)
n=8 Participants
Participants received selinexor dose of 70 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, and 17, followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 11.
|
Selinexor (80 mg/m^2)
n=5 Participants
Participants received selinexor dose of 80 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, and 17, followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 11.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Area Under the Concentration-Time Curve From Time 0 to t (AUC0-t) of Selinexor
|
331 nanogram* hours per milliliter
Geometric Coefficient of Variation NA
Geometric CV was not calculated as data were available for only two participants.
|
564 nanogram* hours per milliliter
Geometric Coefficient of Variation 41.9
|
1459 nanogram* hours per milliliter
Geometric Coefficient of Variation 20.5
|
1829 nanogram* hours per milliliter
Geometric Coefficient of Variation 23.3
|
2774 nanogram* hours per milliliter
Geometric Coefficient of Variation 36.7
|
3461 nanogram* hours per milliliter
Geometric Coefficient of Variation 26.9
|
3901 nanogram* hours per milliliter
Geometric Coefficient of Variation 29.2
|
4481 nanogram* hours per milliliter
Geometric Coefficient of Variation 23.8
|
5228 nanogram* hours per milliliter
Geometric Coefficient of Variation 21.6
|
5601 nanogram* hours per milliliter
Geometric Coefficient of Variation 36.2
|
5282 nanogram* hours per milliliter
Geometric Coefficient of Variation 57.9
|
5466 nanogram* hours per milliliter
Geometric Coefficient of Variation 45.7
|
5544 nanogram* hours per milliliter
Geometric Coefficient of Variation 33.2
|
SECONDARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 2, 4, 8, 24 and 48 hours post-dose on Day 1, 8 of Cycle 1 and Days 15, 16 or 17 of Cycle 2Population: PK analysis was defined as all participants who received active drug, selinexor, without the co-administration of another chemotherapeutic (i.e., rituximab), and for whom the PK profile for C1D1 could be adequately characterized. Here 'Overall Number of Participants Analyzed' signifies number of participants analyzed for this outcome measure.
AUC0-inf was defined as the area under the concentration-time curve from time zero to infinity (extrapolated).
Outcome measures
| Measure |
Diffuse Large B-cell Lymphoma (DLBCL)
n=2 Participants
Participants with DLBCL received Selinexor in different Schedules; Schedule 1: \<= 12 milligram per square meter (mg/m\^2) per orally (PO) alternating 3 times per week with twice weekly dosing (1 day between doses); Schedule 2: \> 12 mg/m\^2 PO 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 8: \>=40 mg/m\^2 PO twice weekly (1 day between doses) during Weeks 1 and 2; Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab intravenous (IV) once weekly for Weeks 1-4 during different cycles. Each cycle was of 28 days (Schedule 8: 21 days of cycle) or 10 scheduled selinexor doses.
|
Non-Hodgkin Lymphoma (NHL) Excluding DLBCL
n=2 Participants
Participants with NHL received Selinexor in different Schedules; Schedule 1: \<= 12 mg/m\^2 PO alternating 3 times per week with twice weekly dosing (1 day between doses); Schedule 2: \> 12 mg/m\^2 PO 3 times weekly for week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs 1 day apart (Schedule 3); Schedule 7: \>=45 mg/m\^2 PO once weekly (6 days between doses) to evaluate vs twice weekly (Schedules 3, 4, 5, and 6); Schedule 8: \>=40 mg/m\^2 PO twice weekly \[1 Day between doses\] during weeks 1 and 2; Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab IV once weekly for Weeks 1-4) during different cycles. Each cycle was of 28 days (Schedule 8: 21 days of cycle) or 10 scheduled selinexor doses.
|
Multiple Myeloma (MM)
n=6 Participants
Participants with MM received Selinexor in different Schedules; Schedule 1: \<= 12 mg/m\^2 PO alternating 3 times per week with twice weekly dosing (1 Day between doses); Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; 3 doses (36 mg/m\^2 total) in the 1-week run-in period; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 6: \>= 35 mg/m\^2 PO twice weekly with dexamethasone (20 mg twice weekly) on Days of twice weekly Selinexor dosing; Schedule 11: Group A: 40 mg; Group B: 60 mg; Group C: 80 mg twice weekly (Weeks 1, 2, and 3) at 3 fixed dose levels during different cycles. Each cycle was of 28 days or 10 scheduled selinexor doses.
|
Acute Myeloid Leukemia (AML)
n=12 Participants
Participants with AML received Selinexor in different Schedules; Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3), Schedule 7: \>=45 mg/m\^2 PO once weekly (6 Days between doses) to evaluate vs. twice weekly (Schedules 3, 4, 5, and 6); Schedule 8: \>=40 mg/m\^2 PO twice weekly (1 Day between doses) during Weeks 1 and 2; Schedule 10: \>= 55 mg/m\^2 PO twice weekly PO (Weeks 1 and 2) in participants with AML/18-Day treatment-free interval) during different cycles. Each cycle was of 28 days (for schedule 8: 21-day of cycle) or 10 scheduled selinexor doses.
|
Other Hematological Malignancies (ALL, CML and CLL)
n=12 Participants
Participants with other hematological malignancies (Acute lymphoblastic leukemia \[ALL\], Chronic myelogenous leukemia \[CML\] and chronic lymphocytic leukemia \[CLL\]) received Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly \[1 day between doses\]; Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 7: \>=45 mg/m\^2 PO once weekly (6 Days between doses) to evaluate vs. twice weekly (Schedules 3, 4, 5, and 6); Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab IV once weekly for Weeks 1-4 during different cycles. Each cycle was of 28 days or 10 scheduled selinexor doses.
|
Selinexor (30 mg/m^2)
n=21 Participants
Participants received selinexor dose of 30 mg/m\^2 orally at Cycle 1, on Day 1, 3, 4, 8, 10, 15 and 17 in schedule 3, 5 and 9.
|
Selinexor (35 mg/m^2)
n=13 Participants
Participants received selinexor dose of 35 mg/m\^2 orally at Cycle 1, on Day 1 and 3 in schedule 6.
|
Selinexor (40 mg/m^2)
n=8 Participants
Participants received selinexor dose of 40 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, 17 followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 8 and 11.
|
Selinexor (46 mg/m^2)
n=9 Participants
Participants received selinexor dose of 46 mg/m\^2 orally at Cycle 1, on Day 1 once-weekly in schedule 7.
|
Selinexor (55 mg/m^2)
n=7 Participants
Participants received selinexor dose of 55 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, and 10, followed by an 18-day treatment-free interval (Days 11 through 28) in schedule 10.
|
Selinexor (60 mg/m^2)
n=3 Participants
Participants received selinexor dose of 60 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, and 17, followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 11.
|
Selinexor (70 mg/m^2)
n=4 Participants
Participants received selinexor dose of 70 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, and 17, followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 11.
|
Selinexor (80 mg/m^2)
n=1 Participants
Participants received selinexor dose of 80 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, and 17, followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 11.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Area Under the Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Selinexor
|
348 ng*h/mL
Geometric Coefficient of Variation NA
Geometric CV was not calculated as data were available for only two participants.
|
733 ng*h/mL
Geometric Coefficient of Variation NA
Geometric CV was not calculated as data were available for only two participants.
|
1529 ng*h/mL
Geometric Coefficient of Variation 18.7
|
1867 ng*h/mL
Geometric Coefficient of Variation 23.6
|
2645 ng*h/mL
Geometric Coefficient of Variation 1111
|
3513 ng*h/mL
Geometric Coefficient of Variation 26.0
|
3948 ng*h/mL
Geometric Coefficient of Variation 28.6
|
4552 ng*h/mL
Geometric Coefficient of Variation 23.7
|
5284 ng*h/mL
Geometric Coefficient of Variation 21.0
|
6089 ng*h/mL
Geometric Coefficient of Variation 32.3
|
6964 ng*h/mL
Geometric Coefficient of Variation 12.2
|
7803 ng*h/mL
Geometric Coefficient of Variation 8.5
|
NA ng*h/mL
Geometric Coefficient of Variation NA
Geometric mean and CV were not calculated as data were available for only one participant.
|
SECONDARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 2, 4, 8, 24 and 48 hours post-dose on Day 1, 8 of Cycle 1 and Days 15, 16 or 17 of Cycle 2Population: PK analysis was defined as all participants who received active drug, selinexor, without the co-administration of another chemotherapeutic (i.e., rituximab), and for whom the PK profile for C1D1 could be adequately characterized. Here 'Overall Number of Participants Analyzed' signifies number of participants analyzed for this outcome measure.
Apparent volume of distribution was calculated as Dose/ (kel \*AUC0-inf), uncorrected for fraction absorbed, reported normalized by participant body weight (kilogram \[kg\]).
Outcome measures
| Measure |
Diffuse Large B-cell Lymphoma (DLBCL)
n=2 Participants
Participants with DLBCL received Selinexor in different Schedules; Schedule 1: \<= 12 milligram per square meter (mg/m\^2) per orally (PO) alternating 3 times per week with twice weekly dosing (1 day between doses); Schedule 2: \> 12 mg/m\^2 PO 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 8: \>=40 mg/m\^2 PO twice weekly (1 day between doses) during Weeks 1 and 2; Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab intravenous (IV) once weekly for Weeks 1-4 during different cycles. Each cycle was of 28 days (Schedule 8: 21 days of cycle) or 10 scheduled selinexor doses.
|
Non-Hodgkin Lymphoma (NHL) Excluding DLBCL
n=2 Participants
Participants with NHL received Selinexor in different Schedules; Schedule 1: \<= 12 mg/m\^2 PO alternating 3 times per week with twice weekly dosing (1 day between doses); Schedule 2: \> 12 mg/m\^2 PO 3 times weekly for week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs 1 day apart (Schedule 3); Schedule 7: \>=45 mg/m\^2 PO once weekly (6 days between doses) to evaluate vs twice weekly (Schedules 3, 4, 5, and 6); Schedule 8: \>=40 mg/m\^2 PO twice weekly \[1 Day between doses\] during weeks 1 and 2; Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab IV once weekly for Weeks 1-4) during different cycles. Each cycle was of 28 days (Schedule 8: 21 days of cycle) or 10 scheduled selinexor doses.
|
Multiple Myeloma (MM)
n=6 Participants
Participants with MM received Selinexor in different Schedules; Schedule 1: \<= 12 mg/m\^2 PO alternating 3 times per week with twice weekly dosing (1 Day between doses); Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; 3 doses (36 mg/m\^2 total) in the 1-week run-in period; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 6: \>= 35 mg/m\^2 PO twice weekly with dexamethasone (20 mg twice weekly) on Days of twice weekly Selinexor dosing; Schedule 11: Group A: 40 mg; Group B: 60 mg; Group C: 80 mg twice weekly (Weeks 1, 2, and 3) at 3 fixed dose levels during different cycles. Each cycle was of 28 days or 10 scheduled selinexor doses.
|
Acute Myeloid Leukemia (AML)
n=12 Participants
Participants with AML received Selinexor in different Schedules; Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3), Schedule 7: \>=45 mg/m\^2 PO once weekly (6 Days between doses) to evaluate vs. twice weekly (Schedules 3, 4, 5, and 6); Schedule 8: \>=40 mg/m\^2 PO twice weekly (1 Day between doses) during Weeks 1 and 2; Schedule 10: \>= 55 mg/m\^2 PO twice weekly PO (Weeks 1 and 2) in participants with AML/18-Day treatment-free interval) during different cycles. Each cycle was of 28 days (for schedule 8: 21-day of cycle) or 10 scheduled selinexor doses.
|
Other Hematological Malignancies (ALL, CML and CLL)
n=12 Participants
Participants with other hematological malignancies (Acute lymphoblastic leukemia \[ALL\], Chronic myelogenous leukemia \[CML\] and chronic lymphocytic leukemia \[CLL\]) received Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly \[1 day between doses\]; Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 7: \>=45 mg/m\^2 PO once weekly (6 Days between doses) to evaluate vs. twice weekly (Schedules 3, 4, 5, and 6); Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab IV once weekly for Weeks 1-4 during different cycles. Each cycle was of 28 days or 10 scheduled selinexor doses.
|
Selinexor (30 mg/m^2)
n=21 Participants
Participants received selinexor dose of 30 mg/m\^2 orally at Cycle 1, on Day 1, 3, 4, 8, 10, 15 and 17 in schedule 3, 5 and 9.
|
Selinexor (35 mg/m^2)
n=13 Participants
Participants received selinexor dose of 35 mg/m\^2 orally at Cycle 1, on Day 1 and 3 in schedule 6.
|
Selinexor (40 mg/m^2)
n=8 Participants
Participants received selinexor dose of 40 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, 17 followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 8 and 11.
|
Selinexor (46 mg/m^2)
n=9 Participants
Participants received selinexor dose of 46 mg/m\^2 orally at Cycle 1, on Day 1 once-weekly in schedule 7.
|
Selinexor (55 mg/m^2)
n=7 Participants
Participants received selinexor dose of 55 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, and 10, followed by an 18-day treatment-free interval (Days 11 through 28) in schedule 10.
|
Selinexor (60 mg/m^2)
n=3 Participants
Participants received selinexor dose of 60 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, and 17, followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 11.
|
Selinexor (70 mg/m^2)
n=4 Participants
Participants received selinexor dose of 70 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, and 17, followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 11.
|
Selinexor (80 mg/m^2)
n=1 Participants
Participants received selinexor dose of 80 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, and 17, followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 11.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Apparent Volume of Distribution Uncorrected for Fraction Absorbed (Vd/F) of Selinexor
|
1.6 Liter per kilogram (L/kg)
Geometric Coefficient of Variation NA
Geometric CV was not calculated as data were available for only two participants.
|
1.5 Liter per kilogram (L/kg)
Geometric Coefficient of Variation NA
Geometric CV was not calculated as data were available for only two participants.
|
1.9 Liter per kilogram (L/kg)
Geometric Coefficient of Variation 21.2
|
1.9 Liter per kilogram (L/kg)
Geometric Coefficient of Variation 29.9
|
1.9 Liter per kilogram (L/kg)
Geometric Coefficient of Variation 34.1
|
1.7 Liter per kilogram (L/kg)
Geometric Coefficient of Variation 24.1
|
2.0 Liter per kilogram (L/kg)
Geometric Coefficient of Variation 30.3
|
1.7 Liter per kilogram (L/kg)
Geometric Coefficient of Variation 29.1
|
1.8 Liter per kilogram (L/kg)
Geometric Coefficient of Variation 12.9
|
1.9 Liter per kilogram (L/kg)
Geometric Coefficient of Variation 27.9
|
1.6 Liter per kilogram (L/kg)
Geometric Coefficient of Variation 23.0
|
1.7 Liter per kilogram (L/kg)
Geometric Coefficient of Variation 13.4
|
NA Liter per kilogram (L/kg)
Geometric Coefficient of Variation NA
Geometric mean and CV were not calculated as data were available for only one participant.
|
SECONDARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 2, 4, 8, 24 and 48 hours post-dose on Day 1, 8 of Cycle 1 and Days 15, 16 or 17 of Cycle 2Population: PK analysis was defined as all participants who received active drug, selinexor, without the co-administration of another chemotherapeutic (i.e., rituximab), and for whom the PK profile for C1D1 could be adequately characterized. Here 'Overall Number of Participants Analyzed' signifies number of participants analyzed for this outcome measure.
Cl/F was calculated as Dose/AUC0-inf, uncorrected for fraction absorbed, reported normalized by participant body weight (kg).
Outcome measures
| Measure |
Diffuse Large B-cell Lymphoma (DLBCL)
n=2 Participants
Participants with DLBCL received Selinexor in different Schedules; Schedule 1: \<= 12 milligram per square meter (mg/m\^2) per orally (PO) alternating 3 times per week with twice weekly dosing (1 day between doses); Schedule 2: \> 12 mg/m\^2 PO 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 8: \>=40 mg/m\^2 PO twice weekly (1 day between doses) during Weeks 1 and 2; Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab intravenous (IV) once weekly for Weeks 1-4 during different cycles. Each cycle was of 28 days (Schedule 8: 21 days of cycle) or 10 scheduled selinexor doses.
|
Non-Hodgkin Lymphoma (NHL) Excluding DLBCL
n=2 Participants
Participants with NHL received Selinexor in different Schedules; Schedule 1: \<= 12 mg/m\^2 PO alternating 3 times per week with twice weekly dosing (1 day between doses); Schedule 2: \> 12 mg/m\^2 PO 3 times weekly for week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs 1 day apart (Schedule 3); Schedule 7: \>=45 mg/m\^2 PO once weekly (6 days between doses) to evaluate vs twice weekly (Schedules 3, 4, 5, and 6); Schedule 8: \>=40 mg/m\^2 PO twice weekly \[1 Day between doses\] during weeks 1 and 2; Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab IV once weekly for Weeks 1-4) during different cycles. Each cycle was of 28 days (Schedule 8: 21 days of cycle) or 10 scheduled selinexor doses.
|
Multiple Myeloma (MM)
n=6 Participants
Participants with MM received Selinexor in different Schedules; Schedule 1: \<= 12 mg/m\^2 PO alternating 3 times per week with twice weekly dosing (1 Day between doses); Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; 3 doses (36 mg/m\^2 total) in the 1-week run-in period; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 6: \>= 35 mg/m\^2 PO twice weekly with dexamethasone (20 mg twice weekly) on Days of twice weekly Selinexor dosing; Schedule 11: Group A: 40 mg; Group B: 60 mg; Group C: 80 mg twice weekly (Weeks 1, 2, and 3) at 3 fixed dose levels during different cycles. Each cycle was of 28 days or 10 scheduled selinexor doses.
|
Acute Myeloid Leukemia (AML)
n=12 Participants
Participants with AML received Selinexor in different Schedules; Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3), Schedule 7: \>=45 mg/m\^2 PO once weekly (6 Days between doses) to evaluate vs. twice weekly (Schedules 3, 4, 5, and 6); Schedule 8: \>=40 mg/m\^2 PO twice weekly (1 Day between doses) during Weeks 1 and 2; Schedule 10: \>= 55 mg/m\^2 PO twice weekly PO (Weeks 1 and 2) in participants with AML/18-Day treatment-free interval) during different cycles. Each cycle was of 28 days (for schedule 8: 21-day of cycle) or 10 scheduled selinexor doses.
|
Other Hematological Malignancies (ALL, CML and CLL)
n=12 Participants
Participants with other hematological malignancies (Acute lymphoblastic leukemia \[ALL\], Chronic myelogenous leukemia \[CML\] and chronic lymphocytic leukemia \[CLL\]) received Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly \[1 day between doses\]; Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 7: \>=45 mg/m\^2 PO once weekly (6 Days between doses) to evaluate vs. twice weekly (Schedules 3, 4, 5, and 6); Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab IV once weekly for Weeks 1-4 during different cycles. Each cycle was of 28 days or 10 scheduled selinexor doses.
|
Selinexor (30 mg/m^2)
n=21 Participants
Participants received selinexor dose of 30 mg/m\^2 orally at Cycle 1, on Day 1, 3, 4, 8, 10, 15 and 17 in schedule 3, 5 and 9.
|
Selinexor (35 mg/m^2)
n=13 Participants
Participants received selinexor dose of 35 mg/m\^2 orally at Cycle 1, on Day 1 and 3 in schedule 6.
|
Selinexor (40 mg/m^2)
n=8 Participants
Participants received selinexor dose of 40 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, 17 followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 8 and 11.
|
Selinexor (46 mg/m^2)
n=9 Participants
Participants received selinexor dose of 46 mg/m\^2 orally at Cycle 1, on Day 1 once-weekly in schedule 7.
|
Selinexor (55 mg/m^2)
n=7 Participants
Participants received selinexor dose of 55 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, and 10, followed by an 18-day treatment-free interval (Days 11 through 28) in schedule 10.
|
Selinexor (60 mg/m^2)
n=3 Participants
Participants received selinexor dose of 60 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, and 17, followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 11.
|
Selinexor (70 mg/m^2)
n=4 Participants
Participants received selinexor dose of 70 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, and 17, followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 11.
|
Selinexor (80 mg/m^2)
n=1 Participants
Participants received selinexor dose of 80 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, and 17, followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 11.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Apparent Total Body Clearance, Uncorrected for Fraction Absorbed (Cl/F) of Selinexor
|
0.19 Liter per hour per kilogram (L/h/kg)
Geometric Coefficient of Variation NA
Geometric CV was not calculated as data were available for only two participants.
|
0.21 Liter per hour per kilogram (L/h/kg)
Geometric Coefficient of Variation NA
Geometric CV was not calculated as data were available for only two participants.
|
0.21 Liter per hour per kilogram (L/h/kg)
Geometric Coefficient of Variation 26.6
|
0.22 Liter per hour per kilogram (L/h/kg)
Geometric Coefficient of Variation 22.8
|
0.20 Liter per hour per kilogram (L/h/kg)
Geometric Coefficient of Variation 54.9
|
0.21 Liter per hour per kilogram (L/h/kg)
Geometric Coefficient of Variation 25.3
|
0.22 Liter per hour per kilogram (L/h/kg)
Geometric Coefficient of Variation 25.9
|
0.23 Liter per hour per kilogram (L/h/kg)
Geometric Coefficient of Variation 26.2
|
0.22 Liter per hour per kilogram (L/h/kg)
Geometric Coefficient of Variation 12.9
|
0.20 Liter per hour per kilogram (L/h/kg)
Geometric Coefficient of Variation 24.6
|
0.19 Liter per hour per kilogram (L/h/kg)
Geometric Coefficient of Variation 27.5
|
0.22 Liter per hour per kilogram (L/h/kg)
Geometric Coefficient of Variation 7.8
|
NA Liter per hour per kilogram (L/h/kg)
Geometric Coefficient of Variation NA
Geometric mean and CV were not calculated as data were available for only one participant.
|
SECONDARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 2, 4, 8, 24 and 48 hours post-dose on Day 1, 8 of Cycle 1 and Days 15, 16 or 17 of Cycle 2Population: PK analysis was defined as all participants who received active drug, selinexor, without the co-administration of another chemotherapeutic (i.e., rituximab), and for whom the PK profile for C1D1 could be adequately characterized. Here 'Overall Number of Participants Analyzed' signifies number of participants analyzed for this outcome measure.
t½ was, calculated as ln(2)/kel, where kel is elimination rate constant, calculated using linear regression on the terminal portion of the log-linear concentration versus time curve.
Outcome measures
| Measure |
Diffuse Large B-cell Lymphoma (DLBCL)
n=2 Participants
Participants with DLBCL received Selinexor in different Schedules; Schedule 1: \<= 12 milligram per square meter (mg/m\^2) per orally (PO) alternating 3 times per week with twice weekly dosing (1 day between doses); Schedule 2: \> 12 mg/m\^2 PO 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 8: \>=40 mg/m\^2 PO twice weekly (1 day between doses) during Weeks 1 and 2; Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab intravenous (IV) once weekly for Weeks 1-4 during different cycles. Each cycle was of 28 days (Schedule 8: 21 days of cycle) or 10 scheduled selinexor doses.
|
Non-Hodgkin Lymphoma (NHL) Excluding DLBCL
n=2 Participants
Participants with NHL received Selinexor in different Schedules; Schedule 1: \<= 12 mg/m\^2 PO alternating 3 times per week with twice weekly dosing (1 day between doses); Schedule 2: \> 12 mg/m\^2 PO 3 times weekly for week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs 1 day apart (Schedule 3); Schedule 7: \>=45 mg/m\^2 PO once weekly (6 days between doses) to evaluate vs twice weekly (Schedules 3, 4, 5, and 6); Schedule 8: \>=40 mg/m\^2 PO twice weekly \[1 Day between doses\] during weeks 1 and 2; Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab IV once weekly for Weeks 1-4) during different cycles. Each cycle was of 28 days (Schedule 8: 21 days of cycle) or 10 scheduled selinexor doses.
|
Multiple Myeloma (MM)
n=6 Participants
Participants with MM received Selinexor in different Schedules; Schedule 1: \<= 12 mg/m\^2 PO alternating 3 times per week with twice weekly dosing (1 Day between doses); Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; 3 doses (36 mg/m\^2 total) in the 1-week run-in period; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 6: \>= 35 mg/m\^2 PO twice weekly with dexamethasone (20 mg twice weekly) on Days of twice weekly Selinexor dosing; Schedule 11: Group A: 40 mg; Group B: 60 mg; Group C: 80 mg twice weekly (Weeks 1, 2, and 3) at 3 fixed dose levels during different cycles. Each cycle was of 28 days or 10 scheduled selinexor doses.
|
Acute Myeloid Leukemia (AML)
n=12 Participants
Participants with AML received Selinexor in different Schedules; Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3), Schedule 7: \>=45 mg/m\^2 PO once weekly (6 Days between doses) to evaluate vs. twice weekly (Schedules 3, 4, 5, and 6); Schedule 8: \>=40 mg/m\^2 PO twice weekly (1 Day between doses) during Weeks 1 and 2; Schedule 10: \>= 55 mg/m\^2 PO twice weekly PO (Weeks 1 and 2) in participants with AML/18-Day treatment-free interval) during different cycles. Each cycle was of 28 days (for schedule 8: 21-day of cycle) or 10 scheduled selinexor doses.
|
Other Hematological Malignancies (ALL, CML and CLL)
n=12 Participants
Participants with other hematological malignancies (Acute lymphoblastic leukemia \[ALL\], Chronic myelogenous leukemia \[CML\] and chronic lymphocytic leukemia \[CLL\]) received Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly \[1 day between doses\]; Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 7: \>=45 mg/m\^2 PO once weekly (6 Days between doses) to evaluate vs. twice weekly (Schedules 3, 4, 5, and 6); Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab IV once weekly for Weeks 1-4 during different cycles. Each cycle was of 28 days or 10 scheduled selinexor doses.
|
Selinexor (30 mg/m^2)
n=21 Participants
Participants received selinexor dose of 30 mg/m\^2 orally at Cycle 1, on Day 1, 3, 4, 8, 10, 15 and 17 in schedule 3, 5 and 9.
|
Selinexor (35 mg/m^2)
n=13 Participants
Participants received selinexor dose of 35 mg/m\^2 orally at Cycle 1, on Day 1 and 3 in schedule 6.
|
Selinexor (40 mg/m^2)
n=8 Participants
Participants received selinexor dose of 40 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, 17 followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 8 and 11.
|
Selinexor (46 mg/m^2)
n=9 Participants
Participants received selinexor dose of 46 mg/m\^2 orally at Cycle 1, on Day 1 once-weekly in schedule 7.
|
Selinexor (55 mg/m^2)
n=7 Participants
Participants received selinexor dose of 55 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, and 10, followed by an 18-day treatment-free interval (Days 11 through 28) in schedule 10.
|
Selinexor (60 mg/m^2)
n=3 Participants
Participants received selinexor dose of 60 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, and 17, followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 11.
|
Selinexor (70 mg/m^2)
n=4 Participants
Participants received selinexor dose of 70 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, and 17, followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 11.
|
Selinexor (80 mg/m^2)
n=1 Participants
Participants received selinexor dose of 80 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, and 17, followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 11.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Terminal Half-Life (t½) of Selinexor
|
NA hour
Interval 5.5 to 6.1
Median value was not calculated due to insufficient PK samples required for calculation.
|
NA hour
Interval 4.4 to 5.1
Median value was not calculated due to insufficient PK samples required for calculation.
|
6.2 hour
Interval 4.2 to 7.8
|
6.1 hour
Interval 3.1 to 8.7
|
6.9 hour
Interval 3.5 to 12.0
|
5.8 hour
Interval 3.9 to 8.4
|
6.2 hour
Interval 4.6 to 10.4
|
4.8 hour
Interval 2.7 to 9.8
|
5.7 hour
Interval 4.1 to 6.8
|
6.6 hour
Interval 5.4 to 10.1
|
5.9 hour
Interval 4.3 to 5.9
|
5.2 hour
Interval 5.0 to 6.0
|
NA hour
Interval 5.5 to 5.5
Median value was not calculated due to insufficient PK samples required for calculation.
|
SECONDARY outcome
Timeframe: From first dose of study drug administration to end of treatment (up to 27 months)Population: Efficacy analysis included all participants registered to the study who had either completed 1 cycle of treatment or discontinued treatment prior to completing the first cycle due to documented disease progression, death related to disease, or treatment-related toxicity.
Objective response for each malignancy was defined using the disease response criteria by malignancy; For NHL (including DLBCL, PTCL, and CTCL), objective response included complete response (CR) and partial response (PR). For MM, objective response included stringent complete response (sCR), CR, very good partial response (VGPR), and PR. For WM, objective response included CR, VGPR, and PR. For CLL, ALL, and AML, objective response included complete remission and Partial remission. For CML, objective response includes complete cytogenic response, and complete hematologic response (CHR).
Outcome measures
| Measure |
Diffuse Large B-cell Lymphoma (DLBCL)
n=58 Participants
Participants with DLBCL received Selinexor in different Schedules; Schedule 1: \<= 12 milligram per square meter (mg/m\^2) per orally (PO) alternating 3 times per week with twice weekly dosing (1 day between doses); Schedule 2: \> 12 mg/m\^2 PO 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 8: \>=40 mg/m\^2 PO twice weekly (1 day between doses) during Weeks 1 and 2; Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab intravenous (IV) once weekly for Weeks 1-4 during different cycles. Each cycle was of 28 days (Schedule 8: 21 days of cycle) or 10 scheduled selinexor doses.
|
Non-Hodgkin Lymphoma (NHL) Excluding DLBCL
n=27 Participants
Participants with NHL received Selinexor in different Schedules; Schedule 1: \<= 12 mg/m\^2 PO alternating 3 times per week with twice weekly dosing (1 day between doses); Schedule 2: \> 12 mg/m\^2 PO 3 times weekly for week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs 1 day apart (Schedule 3); Schedule 7: \>=45 mg/m\^2 PO once weekly (6 days between doses) to evaluate vs twice weekly (Schedules 3, 4, 5, and 6); Schedule 8: \>=40 mg/m\^2 PO twice weekly \[1 Day between doses\] during weeks 1 and 2; Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab IV once weekly for Weeks 1-4) during different cycles. Each cycle was of 28 days (Schedule 8: 21 days of cycle) or 10 scheduled selinexor doses.
|
Multiple Myeloma (MM)
n=81 Participants
Participants with MM received Selinexor in different Schedules; Schedule 1: \<= 12 mg/m\^2 PO alternating 3 times per week with twice weekly dosing (1 Day between doses); Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; 3 doses (36 mg/m\^2 total) in the 1-week run-in period; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 6: \>= 35 mg/m\^2 PO twice weekly with dexamethasone (20 mg twice weekly) on Days of twice weekly Selinexor dosing; Schedule 11: Group A: 40 mg; Group B: 60 mg; Group C: 80 mg twice weekly (Weeks 1, 2, and 3) at 3 fixed dose levels during different cycles. Each cycle was of 28 days or 10 scheduled selinexor doses.
|
Acute Myeloid Leukemia (AML)
n=95 Participants
Participants with AML received Selinexor in different Schedules; Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3), Schedule 7: \>=45 mg/m\^2 PO once weekly (6 Days between doses) to evaluate vs. twice weekly (Schedules 3, 4, 5, and 6); Schedule 8: \>=40 mg/m\^2 PO twice weekly (1 Day between doses) during Weeks 1 and 2; Schedule 10: \>= 55 mg/m\^2 PO twice weekly PO (Weeks 1 and 2) in participants with AML/18-Day treatment-free interval) during different cycles. Each cycle was of 28 days (for schedule 8: 21-day of cycle) or 10 scheduled selinexor doses.
|
Other Hematological Malignancies (ALL, CML and CLL)
n=24 Participants
Participants with other hematological malignancies (Acute lymphoblastic leukemia \[ALL\], Chronic myelogenous leukemia \[CML\] and chronic lymphocytic leukemia \[CLL\]) received Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly \[1 day between doses\]; Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 7: \>=45 mg/m\^2 PO once weekly (6 Days between doses) to evaluate vs. twice weekly (Schedules 3, 4, 5, and 6); Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab IV once weekly for Weeks 1-4 during different cycles. Each cycle was of 28 days or 10 scheduled selinexor doses.
|
Selinexor (30 mg/m^2)
Participants received selinexor dose of 30 mg/m\^2 orally at Cycle 1, on Day 1, 3, 4, 8, 10, 15 and 17 in schedule 3, 5 and 9.
|
Selinexor (35 mg/m^2)
Participants received selinexor dose of 35 mg/m\^2 orally at Cycle 1, on Day 1 and 3 in schedule 6.
|
Selinexor (40 mg/m^2)
Participants received selinexor dose of 40 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, 17 followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 8 and 11.
|
Selinexor (46 mg/m^2)
Participants received selinexor dose of 46 mg/m\^2 orally at Cycle 1, on Day 1 once-weekly in schedule 7.
|
Selinexor (55 mg/m^2)
Participants received selinexor dose of 55 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, and 10, followed by an 18-day treatment-free interval (Days 11 through 28) in schedule 10.
|
Selinexor (60 mg/m^2)
Participants received selinexor dose of 60 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, and 17, followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 11.
|
Selinexor (70 mg/m^2)
Participants received selinexor dose of 70 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, and 17, followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 11.
|
Selinexor (80 mg/m^2)
Participants received selinexor dose of 80 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, and 17, followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 11.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Number of Participants With Overall Response of Selinexor
Complete response
|
5 participants
|
1 participants
|
0 participants
|
0 participants
|
0 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Overall Response of Selinexor
Partial response
|
7 participants
|
8 participants
|
6 participants
|
0 participants
|
0 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Overall Response of Selinexor
Morphologic complete remission
|
0 participants
|
0 participants
|
0 participants
|
4 participants
|
0 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Overall Response of Selinexor
Partial remission
|
0 participants
|
0 participants
|
0 participants
|
3 participants
|
1 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Overall Response of Selinexor
Complete cytogenetic response
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Overall Response of Selinexor
Complete hematological response
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From first dose of study drug administration to end of treatment (up to 27 months)Population: Efficacy analysis included all participants who had either completed 1 cycle of treatment or discontinued treatment prior to completing the first cycle due to documented disease progression, death related to disease, or treatment-related toxicity. Here 'Overall Number of Participants Analyzed' signifies number of participants analyzed for this outcome measure.
Duration of response was defined as the time from the first occurrence of objective response to first documented evidence of disease recurrence or progression. Participants without evidence of progression were censored at time of last evaluable disease assessment. Objective response was defined as any response of partial response/remission or better for all malignancies; for AML, a response of morphologic leukemia-free state is also included for ORR. Duration of response was calculated by Kaplan-Meier method.
Outcome measures
| Measure |
Diffuse Large B-cell Lymphoma (DLBCL)
n=12 Participants
Participants with DLBCL received Selinexor in different Schedules; Schedule 1: \<= 12 milligram per square meter (mg/m\^2) per orally (PO) alternating 3 times per week with twice weekly dosing (1 day between doses); Schedule 2: \> 12 mg/m\^2 PO 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 8: \>=40 mg/m\^2 PO twice weekly (1 day between doses) during Weeks 1 and 2; Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab intravenous (IV) once weekly for Weeks 1-4 during different cycles. Each cycle was of 28 days (Schedule 8: 21 days of cycle) or 10 scheduled selinexor doses.
|
Non-Hodgkin Lymphoma (NHL) Excluding DLBCL
n=9 Participants
Participants with NHL received Selinexor in different Schedules; Schedule 1: \<= 12 mg/m\^2 PO alternating 3 times per week with twice weekly dosing (1 day between doses); Schedule 2: \> 12 mg/m\^2 PO 3 times weekly for week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs 1 day apart (Schedule 3); Schedule 7: \>=45 mg/m\^2 PO once weekly (6 days between doses) to evaluate vs twice weekly (Schedules 3, 4, 5, and 6); Schedule 8: \>=40 mg/m\^2 PO twice weekly \[1 Day between doses\] during weeks 1 and 2; Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab IV once weekly for Weeks 1-4) during different cycles. Each cycle was of 28 days (Schedule 8: 21 days of cycle) or 10 scheduled selinexor doses.
|
Multiple Myeloma (MM)
n=7 Participants
Participants with MM received Selinexor in different Schedules; Schedule 1: \<= 12 mg/m\^2 PO alternating 3 times per week with twice weekly dosing (1 Day between doses); Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; 3 doses (36 mg/m\^2 total) in the 1-week run-in period; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 6: \>= 35 mg/m\^2 PO twice weekly with dexamethasone (20 mg twice weekly) on Days of twice weekly Selinexor dosing; Schedule 11: Group A: 40 mg; Group B: 60 mg; Group C: 80 mg twice weekly (Weeks 1, 2, and 3) at 3 fixed dose levels during different cycles. Each cycle was of 28 days or 10 scheduled selinexor doses.
|
Acute Myeloid Leukemia (AML)
n=11 Participants
Participants with AML received Selinexor in different Schedules; Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3), Schedule 7: \>=45 mg/m\^2 PO once weekly (6 Days between doses) to evaluate vs. twice weekly (Schedules 3, 4, 5, and 6); Schedule 8: \>=40 mg/m\^2 PO twice weekly (1 Day between doses) during Weeks 1 and 2; Schedule 10: \>= 55 mg/m\^2 PO twice weekly PO (Weeks 1 and 2) in participants with AML/18-Day treatment-free interval) during different cycles. Each cycle was of 28 days (for schedule 8: 21-day of cycle) or 10 scheduled selinexor doses.
|
Other Hematological Malignancies (ALL, CML and CLL)
n=1 Participants
Participants with other hematological malignancies (Acute lymphoblastic leukemia \[ALL\], Chronic myelogenous leukemia \[CML\] and chronic lymphocytic leukemia \[CLL\]) received Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly \[1 day between doses\]; Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 7: \>=45 mg/m\^2 PO once weekly (6 Days between doses) to evaluate vs. twice weekly (Schedules 3, 4, 5, and 6); Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab IV once weekly for Weeks 1-4 during different cycles. Each cycle was of 28 days or 10 scheduled selinexor doses.
|
Selinexor (30 mg/m^2)
Participants received selinexor dose of 30 mg/m\^2 orally at Cycle 1, on Day 1, 3, 4, 8, 10, 15 and 17 in schedule 3, 5 and 9.
|
Selinexor (35 mg/m^2)
Participants received selinexor dose of 35 mg/m\^2 orally at Cycle 1, on Day 1 and 3 in schedule 6.
|
Selinexor (40 mg/m^2)
Participants received selinexor dose of 40 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, 17 followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 8 and 11.
|
Selinexor (46 mg/m^2)
Participants received selinexor dose of 46 mg/m\^2 orally at Cycle 1, on Day 1 once-weekly in schedule 7.
|
Selinexor (55 mg/m^2)
Participants received selinexor dose of 55 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, and 10, followed by an 18-day treatment-free interval (Days 11 through 28) in schedule 10.
|
Selinexor (60 mg/m^2)
Participants received selinexor dose of 60 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, and 17, followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 11.
|
Selinexor (70 mg/m^2)
Participants received selinexor dose of 70 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, and 17, followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 11.
|
Selinexor (80 mg/m^2)
Participants received selinexor dose of 80 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, and 17, followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 11.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Duration of Response
|
335.5 Days
Interval 48.0 to
Upper limit of 95% Confidence Interval (CI) was not estimable due to less than 50% death events.
|
251 Days
Interval 36.0 to
Upper limit of 95% CI was not estimable due to less than 50% death events.
|
180 Days
Interval 57.0 to
Upper limit of 95% CI was not estimable due to less than 50% death events.
|
76 Days
Interval 29.0 to
Upper limit of 95% CI was not estimable due to less than 50% death events.
|
NA Days
Median and limits of 95% CI were not estimable due to less than 50% death events.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 Day 1 to End of Treatment (up to 27 months)Population: Efficacy analysis included all participants registered to the study who had either completed 1 cycle of treatment or discontinued treatment prior to completing the first cycle due to documented disease progression, death related to disease, or treatment-related toxicity.
Progression-free survival (PFS) was calculated from the date of first dose of study drug to first documented evidence of disease recurrence or progression or death due to any cause. Participants who were last known to be alive and without evidence of progression were censored at time of last evaluable disease assessment. If date of progression or death occurred after more than 1 missed disease assessment interval, participants were censored at the time of last evaluable disease assessment prior to the missed assessment.
Outcome measures
| Measure |
Diffuse Large B-cell Lymphoma (DLBCL)
n=58 Participants
Participants with DLBCL received Selinexor in different Schedules; Schedule 1: \<= 12 milligram per square meter (mg/m\^2) per orally (PO) alternating 3 times per week with twice weekly dosing (1 day between doses); Schedule 2: \> 12 mg/m\^2 PO 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 8: \>=40 mg/m\^2 PO twice weekly (1 day between doses) during Weeks 1 and 2; Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab intravenous (IV) once weekly for Weeks 1-4 during different cycles. Each cycle was of 28 days (Schedule 8: 21 days of cycle) or 10 scheduled selinexor doses.
|
Non-Hodgkin Lymphoma (NHL) Excluding DLBCL
n=27 Participants
Participants with NHL received Selinexor in different Schedules; Schedule 1: \<= 12 mg/m\^2 PO alternating 3 times per week with twice weekly dosing (1 day between doses); Schedule 2: \> 12 mg/m\^2 PO 3 times weekly for week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs 1 day apart (Schedule 3); Schedule 7: \>=45 mg/m\^2 PO once weekly (6 days between doses) to evaluate vs twice weekly (Schedules 3, 4, 5, and 6); Schedule 8: \>=40 mg/m\^2 PO twice weekly \[1 Day between doses\] during weeks 1 and 2; Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab IV once weekly for Weeks 1-4) during different cycles. Each cycle was of 28 days (Schedule 8: 21 days of cycle) or 10 scheduled selinexor doses.
|
Multiple Myeloma (MM)
n=81 Participants
Participants with MM received Selinexor in different Schedules; Schedule 1: \<= 12 mg/m\^2 PO alternating 3 times per week with twice weekly dosing (1 Day between doses); Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; 3 doses (36 mg/m\^2 total) in the 1-week run-in period; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 6: \>= 35 mg/m\^2 PO twice weekly with dexamethasone (20 mg twice weekly) on Days of twice weekly Selinexor dosing; Schedule 11: Group A: 40 mg; Group B: 60 mg; Group C: 80 mg twice weekly (Weeks 1, 2, and 3) at 3 fixed dose levels during different cycles. Each cycle was of 28 days or 10 scheduled selinexor doses.
|
Acute Myeloid Leukemia (AML)
n=95 Participants
Participants with AML received Selinexor in different Schedules; Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3), Schedule 7: \>=45 mg/m\^2 PO once weekly (6 Days between doses) to evaluate vs. twice weekly (Schedules 3, 4, 5, and 6); Schedule 8: \>=40 mg/m\^2 PO twice weekly (1 Day between doses) during Weeks 1 and 2; Schedule 10: \>= 55 mg/m\^2 PO twice weekly PO (Weeks 1 and 2) in participants with AML/18-Day treatment-free interval) during different cycles. Each cycle was of 28 days (for schedule 8: 21-day of cycle) or 10 scheduled selinexor doses.
|
Other Hematological Malignancies (ALL, CML and CLL)
n=24 Participants
Participants with other hematological malignancies (Acute lymphoblastic leukemia \[ALL\], Chronic myelogenous leukemia \[CML\] and chronic lymphocytic leukemia \[CLL\]) received Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly \[1 day between doses\]; Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 7: \>=45 mg/m\^2 PO once weekly (6 Days between doses) to evaluate vs. twice weekly (Schedules 3, 4, 5, and 6); Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab IV once weekly for Weeks 1-4 during different cycles. Each cycle was of 28 days or 10 scheduled selinexor doses.
|
Selinexor (30 mg/m^2)
Participants received selinexor dose of 30 mg/m\^2 orally at Cycle 1, on Day 1, 3, 4, 8, 10, 15 and 17 in schedule 3, 5 and 9.
|
Selinexor (35 mg/m^2)
Participants received selinexor dose of 35 mg/m\^2 orally at Cycle 1, on Day 1 and 3 in schedule 6.
|
Selinexor (40 mg/m^2)
Participants received selinexor dose of 40 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, 17 followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 8 and 11.
|
Selinexor (46 mg/m^2)
Participants received selinexor dose of 46 mg/m\^2 orally at Cycle 1, on Day 1 once-weekly in schedule 7.
|
Selinexor (55 mg/m^2)
Participants received selinexor dose of 55 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, and 10, followed by an 18-day treatment-free interval (Days 11 through 28) in schedule 10.
|
Selinexor (60 mg/m^2)
Participants received selinexor dose of 60 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, and 17, followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 11.
|
Selinexor (70 mg/m^2)
Participants received selinexor dose of 70 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, and 17, followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 11.
|
Selinexor (80 mg/m^2)
Participants received selinexor dose of 80 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, and 17, followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 11.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Progression-free Survival
|
47 Days
Interval 31.0 to 56.0
|
110 Days
Interval 28.0 to 274.0
|
57 Days
Interval 36.0 to 88.0
|
44 Days
Interval 36.0 to 52.0
|
57 Days
Interval 24.0 to 222.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 Day 1 to End of Treatment (up to 27 months)Population: Efficacy analysis included all participants registered to the study who had either completed 1 cycle of treatment or discontinued treatment prior to completing the first cycle due to documented disease progression, death related to disease, or treatment-related toxicity.
Duration of at least stable disease was defined as the time from the date of first dose of study drug to first documented evidence of disease recurrence or progression. Participants without evidence of progression were censored at time of last evaluable disease assessment.
Outcome measures
| Measure |
Diffuse Large B-cell Lymphoma (DLBCL)
n=58 Participants
Participants with DLBCL received Selinexor in different Schedules; Schedule 1: \<= 12 milligram per square meter (mg/m\^2) per orally (PO) alternating 3 times per week with twice weekly dosing (1 day between doses); Schedule 2: \> 12 mg/m\^2 PO 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 8: \>=40 mg/m\^2 PO twice weekly (1 day between doses) during Weeks 1 and 2; Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab intravenous (IV) once weekly for Weeks 1-4 during different cycles. Each cycle was of 28 days (Schedule 8: 21 days of cycle) or 10 scheduled selinexor doses.
|
Non-Hodgkin Lymphoma (NHL) Excluding DLBCL
n=27 Participants
Participants with NHL received Selinexor in different Schedules; Schedule 1: \<= 12 mg/m\^2 PO alternating 3 times per week with twice weekly dosing (1 day between doses); Schedule 2: \> 12 mg/m\^2 PO 3 times weekly for week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs 1 day apart (Schedule 3); Schedule 7: \>=45 mg/m\^2 PO once weekly (6 days between doses) to evaluate vs twice weekly (Schedules 3, 4, 5, and 6); Schedule 8: \>=40 mg/m\^2 PO twice weekly \[1 Day between doses\] during weeks 1 and 2; Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab IV once weekly for Weeks 1-4) during different cycles. Each cycle was of 28 days (Schedule 8: 21 days of cycle) or 10 scheduled selinexor doses.
|
Multiple Myeloma (MM)
n=81 Participants
Participants with MM received Selinexor in different Schedules; Schedule 1: \<= 12 mg/m\^2 PO alternating 3 times per week with twice weekly dosing (1 Day between doses); Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; 3 doses (36 mg/m\^2 total) in the 1-week run-in period; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 6: \>= 35 mg/m\^2 PO twice weekly with dexamethasone (20 mg twice weekly) on Days of twice weekly Selinexor dosing; Schedule 11: Group A: 40 mg; Group B: 60 mg; Group C: 80 mg twice weekly (Weeks 1, 2, and 3) at 3 fixed dose levels during different cycles. Each cycle was of 28 days or 10 scheduled selinexor doses.
|
Acute Myeloid Leukemia (AML)
n=95 Participants
Participants with AML received Selinexor in different Schedules; Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3), Schedule 7: \>=45 mg/m\^2 PO once weekly (6 Days between doses) to evaluate vs. twice weekly (Schedules 3, 4, 5, and 6); Schedule 8: \>=40 mg/m\^2 PO twice weekly (1 Day between doses) during Weeks 1 and 2; Schedule 10: \>= 55 mg/m\^2 PO twice weekly PO (Weeks 1 and 2) in participants with AML/18-Day treatment-free interval) during different cycles. Each cycle was of 28 days (for schedule 8: 21-day of cycle) or 10 scheduled selinexor doses.
|
Other Hematological Malignancies (ALL, CML and CLL)
n=24 Participants
Participants with other hematological malignancies (Acute lymphoblastic leukemia \[ALL\], Chronic myelogenous leukemia \[CML\] and chronic lymphocytic leukemia \[CLL\]) received Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly \[1 day between doses\]; Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 7: \>=45 mg/m\^2 PO once weekly (6 Days between doses) to evaluate vs. twice weekly (Schedules 3, 4, 5, and 6); Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab IV once weekly for Weeks 1-4 during different cycles. Each cycle was of 28 days or 10 scheduled selinexor doses.
|
Selinexor (30 mg/m^2)
Participants received selinexor dose of 30 mg/m\^2 orally at Cycle 1, on Day 1, 3, 4, 8, 10, 15 and 17 in schedule 3, 5 and 9.
|
Selinexor (35 mg/m^2)
Participants received selinexor dose of 35 mg/m\^2 orally at Cycle 1, on Day 1 and 3 in schedule 6.
|
Selinexor (40 mg/m^2)
Participants received selinexor dose of 40 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, 17 followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 8 and 11.
|
Selinexor (46 mg/m^2)
Participants received selinexor dose of 46 mg/m\^2 orally at Cycle 1, on Day 1 once-weekly in schedule 7.
|
Selinexor (55 mg/m^2)
Participants received selinexor dose of 55 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, and 10, followed by an 18-day treatment-free interval (Days 11 through 28) in schedule 10.
|
Selinexor (60 mg/m^2)
Participants received selinexor dose of 60 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, and 17, followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 11.
|
Selinexor (70 mg/m^2)
Participants received selinexor dose of 70 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, and 17, followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 11.
|
Selinexor (80 mg/m^2)
Participants received selinexor dose of 80 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, and 17, followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 11.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Duration of at Least Stable Disease
|
52 Days
Interval 32.0 to 79.0
|
114 Days
Interval 43.0 to 415.0
|
57 Days
Interval 43.0 to 100.0
|
80 Days
Interval 52.0 to 101.0
|
64 Days
Interval 21.0 to 283.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 Day 1 to End of Treatment (up to 27 months)Population: Efficacy analysis included all participants registered to the study who had either completed 1 cycle of treatment or discontinued treatment prior to completing the first cycle due to documented disease progression, death related to disease, or treatment-related toxicity.
Overall Survival was calculated from the date of first dose of study drug to date of death due to any cause. Participants who were last known to be alive were censored at time of last contact. Overall survival was calculated by Kaplan-Meier method.
Outcome measures
| Measure |
Diffuse Large B-cell Lymphoma (DLBCL)
n=58 Participants
Participants with DLBCL received Selinexor in different Schedules; Schedule 1: \<= 12 milligram per square meter (mg/m\^2) per orally (PO) alternating 3 times per week with twice weekly dosing (1 day between doses); Schedule 2: \> 12 mg/m\^2 PO 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 8: \>=40 mg/m\^2 PO twice weekly (1 day between doses) during Weeks 1 and 2; Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab intravenous (IV) once weekly for Weeks 1-4 during different cycles. Each cycle was of 28 days (Schedule 8: 21 days of cycle) or 10 scheduled selinexor doses.
|
Non-Hodgkin Lymphoma (NHL) Excluding DLBCL
n=27 Participants
Participants with NHL received Selinexor in different Schedules; Schedule 1: \<= 12 mg/m\^2 PO alternating 3 times per week with twice weekly dosing (1 day between doses); Schedule 2: \> 12 mg/m\^2 PO 3 times weekly for week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs 1 day apart (Schedule 3); Schedule 7: \>=45 mg/m\^2 PO once weekly (6 days between doses) to evaluate vs twice weekly (Schedules 3, 4, 5, and 6); Schedule 8: \>=40 mg/m\^2 PO twice weekly \[1 Day between doses\] during weeks 1 and 2; Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab IV once weekly for Weeks 1-4) during different cycles. Each cycle was of 28 days (Schedule 8: 21 days of cycle) or 10 scheduled selinexor doses.
|
Multiple Myeloma (MM)
n=81 Participants
Participants with MM received Selinexor in different Schedules; Schedule 1: \<= 12 mg/m\^2 PO alternating 3 times per week with twice weekly dosing (1 Day between doses); Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; 3 doses (36 mg/m\^2 total) in the 1-week run-in period; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 6: \>= 35 mg/m\^2 PO twice weekly with dexamethasone (20 mg twice weekly) on Days of twice weekly Selinexor dosing; Schedule 11: Group A: 40 mg; Group B: 60 mg; Group C: 80 mg twice weekly (Weeks 1, 2, and 3) at 3 fixed dose levels during different cycles. Each cycle was of 28 days or 10 scheduled selinexor doses.
|
Acute Myeloid Leukemia (AML)
n=95 Participants
Participants with AML received Selinexor in different Schedules; Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3), Schedule 7: \>=45 mg/m\^2 PO once weekly (6 Days between doses) to evaluate vs. twice weekly (Schedules 3, 4, 5, and 6); Schedule 8: \>=40 mg/m\^2 PO twice weekly (1 Day between doses) during Weeks 1 and 2; Schedule 10: \>= 55 mg/m\^2 PO twice weekly PO (Weeks 1 and 2) in participants with AML/18-Day treatment-free interval) during different cycles. Each cycle was of 28 days (for schedule 8: 21-day of cycle) or 10 scheduled selinexor doses.
|
Other Hematological Malignancies (ALL, CML and CLL)
n=24 Participants
Participants with other hematological malignancies (Acute lymphoblastic leukemia \[ALL\], Chronic myelogenous leukemia \[CML\] and chronic lymphocytic leukemia \[CLL\]) received Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly \[1 day between doses\]; Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 7: \>=45 mg/m\^2 PO once weekly (6 Days between doses) to evaluate vs. twice weekly (Schedules 3, 4, 5, and 6); Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab IV once weekly for Weeks 1-4 during different cycles. Each cycle was of 28 days or 10 scheduled selinexor doses.
|
Selinexor (30 mg/m^2)
Participants received selinexor dose of 30 mg/m\^2 orally at Cycle 1, on Day 1, 3, 4, 8, 10, 15 and 17 in schedule 3, 5 and 9.
|
Selinexor (35 mg/m^2)
Participants received selinexor dose of 35 mg/m\^2 orally at Cycle 1, on Day 1 and 3 in schedule 6.
|
Selinexor (40 mg/m^2)
Participants received selinexor dose of 40 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, 17 followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 8 and 11.
|
Selinexor (46 mg/m^2)
Participants received selinexor dose of 46 mg/m\^2 orally at Cycle 1, on Day 1 once-weekly in schedule 7.
|
Selinexor (55 mg/m^2)
Participants received selinexor dose of 55 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, and 10, followed by an 18-day treatment-free interval (Days 11 through 28) in schedule 10.
|
Selinexor (60 mg/m^2)
Participants received selinexor dose of 60 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, and 17, followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 11.
|
Selinexor (70 mg/m^2)
Participants received selinexor dose of 70 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, and 17, followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 11.
|
Selinexor (80 mg/m^2)
Participants received selinexor dose of 80 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, and 17, followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 11.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Overall Survival
|
138 Days
Interval 85.0 to
Upper limit of 95% CI was not estimable due to less than 50% death events.
|
423 Days
Interval 423.0 to
Upper limit of 95% CI was not estimable due to less than 50% death events.
|
366 Days
Interval 126.0 to
Upper limit of 95% CI was not estimable due to less than 50% death events.
|
76 Days
Interval 48.0 to 114.0
|
82 Days
Interval 50.0 to
Upper limit of 95% CI was not estimable due to less than 50% death events.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
Adverse Events
Diffuse Large B-cell Lymphoma (DLBCL)
Serious events: 33 serious events
Other events: 58 other events
Deaths: 0 deaths
Non-Hodgkin Lymphoma (NHL) Excluding DLBCL
Serious events: 7 serious events
Other events: 27 other events
Deaths: 0 deaths
Multiple Myeloma (MM)
Serious events: 52 serious events
Other events: 80 other events
Deaths: 0 deaths
Acute Myeloid Leukemia (AML)
Serious events: 73 serious events
Other events: 94 other events
Deaths: 0 deaths
Other Hematological Malignancies (ALL, CML and CLL)
Serious events: 13 serious events
Other events: 24 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Diffuse Large B-cell Lymphoma (DLBCL)
n=58 participants at risk
Participants with DLBCL received Selinexor in different Schedules; Schedule 1: \<= 12 milligram per square meter (mg/m\^2) per orally (PO) alternating 3 times per week with twice weekly dosing (1 day between doses); Schedule 2: \> 12 mg/m\^2 PO 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 8: \>=40 mg/m\^2 PO twice weekly (1 day between doses) during Weeks 1 and 2; Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab intravenous (IV) once weekly for Weeks 1-4 during different cycles. Each cycle was of 28 days (Schedule 8: 21 days of cycle) or 10 scheduled selinexor doses.
|
Non-Hodgkin Lymphoma (NHL) Excluding DLBCL
n=27 participants at risk
Participants with NHL received Selinexor in different Schedules; Schedule 1: \<= 12 mg/m\^2 PO alternating 3 times per week with twice weekly dosing (1 day between doses); Schedule 2: \> 12 mg/m\^2 PO 3 times weekly for week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs 1 day apart (Schedule 3); Schedule 7: \>=45 mg/m\^2 PO once weekly (6 days between doses) to evaluate vs twice weekly (Schedules 3, 4, 5, and 6); Schedule 8: \>=40 mg/m\^2 PO twice weekly \[1 Day between doses\] during weeks 1 and 2; Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab IV once weekly for Weeks 1-4) during different cycles. Each cycle was of 28 days (Schedule 8: 21 days of cycle) or 10 scheduled selinexor doses.
|
Multiple Myeloma (MM)
n=81 participants at risk
Participants with MM received Selinexor in different Schedules; Schedule 1: \<= 12 mg/m\^2 PO alternating 3 times per week with twice weekly dosing (1 Day between doses); Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; 3 doses (36 mg/m\^2 total) in the 1-week run-in period; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 6: \>= 35 mg/m\^2 PO twice weekly with dexamethasone (20 mg twice weekly) on Days of twice weekly Selinexor dosing; Schedule 11: Group A: 40 mg; Group B: 60 mg; Group C: 80 mg twice weekly (Weeks 1, 2, and 3) at 3 fixed dose levels during different cycles. Each cycle was of 28 days or 10 scheduled selinexor doses.
|
Acute Myeloid Leukemia (AML)
n=95 participants at risk
Participants with AML received Selinexor in different Schedules; Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3), Schedule 7: \>=45 mg/m\^2 PO once weekly (6 Days between doses) to evaluate vs. twice weekly (Schedules 3, 4, 5, and 6); Schedule 8: \>=40 mg/m\^2 PO twice weekly (1 Day between doses) during Weeks 1 and 2; Schedule 10: \>= 55 mg/m\^2 PO twice weekly PO (Weeks 1 and 2) in participants with AML/18-Day treatment-free interval) during different cycles. Each cycle was of 28 days (for schedule 8: 21-day of cycle) or 10 scheduled selinexor doses.
|
Other Hematological Malignancies (ALL, CML and CLL)
n=24 participants at risk
Participants with other hematological malignancies (Acute lymphoblastic leukemia \[ALL\], Chronic myelogenous leukemia \[CML\] and chronic lymphocytic leukemia \[CLL\]) received Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly \[1 day between doses\]; Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 7: \>=45 mg/m\^2 PO once weekly (6 Days between doses) to evaluate vs. twice weekly (Schedules 3, 4, 5, and 6); Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab IV once weekly for Weeks 1-4 during different cycles. Each cycle was of 28 days or 10 scheduled selinexor doses.
|
|---|---|---|---|---|---|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Musculoskeletal and connective tissue disorders
Joint effusion
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Metabolism and nutrition disorders
Dehydration
|
3.4%
2/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.7%
3/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
5.3%
5/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.7%
1/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
2.5%
2/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
4.2%
1/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Metabolism and nutrition disorders
Fluid overload
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
2.5%
2/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.2%
1/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
4.2%
1/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
1.7%
1/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.7%
1/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Metabolism and nutrition disorders
Hyperamylasaemia
|
1.7%
1/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Vascular disorders
Embolism
|
3.4%
2/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
2.1%
2/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Vascular disorders
Hypotension
|
1.7%
1/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
2.5%
2/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Surgical and medical procedures
Small intestinal resection
|
1.7%
1/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.2%
1/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
4.2%
4/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.7%
1/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
General disorders
Pyrexia
|
5.2%
3/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
6.2%
5/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
General disorders
Fatigue
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.2%
1/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
6.3%
6/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
General disorders
Death
|
1.7%
1/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.2%
3/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
4.2%
1/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
General disorders
Asthenia
|
1.7%
1/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
2.5%
2/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
General disorders
Disease progression
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
2.1%
2/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
General disorders
Multiple organ dysfunction syndrome
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
2.1%
2/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
General disorders
Gait disturbance
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
4.2%
1/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.2%
1/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
General disorders
Pain
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
General disorders
Performance status decreased
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
General disorders
Sudden death
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
General disorders
Unevaluable event
|
1.7%
1/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
General disorders
Confusional state
|
5.2%
3/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.2%
1/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Psychiatric disorders
Delirium
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
2.5%
2/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Psychiatric disorders
Suicide attempt
|
1.7%
1/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.7%
1/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Psychiatric disorders
Psychotic disorder
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.2%
1/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Injury, poisoning and procedural complications
Fall
|
1.7%
1/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.2%
1/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
2.1%
2/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Injury, poisoning and procedural complications
Overdose
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
4.2%
1/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Injury, poisoning and procedural complications
Post procedural haemorrhage
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Injury, poisoning and procedural complications
Rib fracture
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.2%
1/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Injury, poisoning and procedural complications
Spinal fracture
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Injury, poisoning and procedural complications
Transfusion reaction
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Injury, poisoning and procedural complications
Wrist fracture
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
2.5%
2/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Investigations
Ejection fraction decreased
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
4.2%
1/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.2%
1/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Injury, poisoning and procedural complications
Blood alkaline phosphatase increased
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.2%
1/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Cardiac disorders
Tachycardia
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
2.1%
2/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Cardiac disorders
Cardiac arrest
|
1.7%
1/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Cardiac disorders
Cardiac failure
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.2%
1/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Cardiac disorders
Left ventricular dysfunction
|
1.7%
1/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Cardiac disorders
Palpitations
|
1.7%
1/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
2.5%
2/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
2.1%
2/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
1.7%
1/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
4.2%
1/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.2%
1/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
2.1%
2/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.2%
3/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
2.1%
2/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
1.7%
1/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration
|
1.7%
1/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.2%
1/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
1.7%
1/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.7%
1/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.2%
1/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Respiratory, thoracic and mediastinal disorders
Lung consolidation
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
4.2%
1/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
1.7%
1/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory arrest
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
4.2%
1/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
6.9%
4/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.7%
1/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
7.4%
6/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
12.6%
12/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
4.9%
4/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
2.1%
2/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Blood and lymphatic system disorders
Anaemia
|
3.4%
2/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
2.5%
2/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Blood and lymphatic system disorders
Hyperviscosity syndrome
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.2%
1/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Blood and lymphatic system disorders
Leukocytosis
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Blood and lymphatic system disorders
Leukostasis syndrome
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Blood and lymphatic system disorders
Pancytopenia
|
1.7%
1/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Nervous system disorders
Central nervous system haemorrhage
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
2.1%
2/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Nervous system disorders
Cerebral haemorrhage
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.2%
1/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Nervous system disorders
Encephalopathy
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.2%
1/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Nervous system disorders
Seizure
|
1.7%
1/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Nervous system disorders
Dysarthria
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.2%
1/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Nervous system disorders
Encephalitis toxic
|
1.7%
1/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Nervous system disorders
Facial paralysis
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.2%
1/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Nervous system disorders
Guillain-Barre syndrome
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Nervous system disorders
Haemorrhage intracranial
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Nervous system disorders
Lethargy
|
1.7%
1/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Nervous system disorders
Nervous system disorder
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Nervous system disorders
Somnolence
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Nervous system disorders
Spinal cord compression
|
1.7%
1/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Nervous system disorders
Syncope
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Nervous system disorders
Transient ischaemic attack
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
4.2%
1/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Eye disorders
Cataract
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.7%
1/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Eye disorders
Eye haemorrhage
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.2%
1/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Eye disorders
Retinal detachment
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.2%
1/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Eye disorders
Vision blurred
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.2%
1/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Eye disorders
Vitreous detachment
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.2%
1/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Gastrointestinal disorders
Vomiting
|
3.4%
2/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.2%
1/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.2%
3/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
4.2%
1/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.2%
1/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Gastrointestinal disorders
Ascites
|
1.7%
1/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Gastrointestinal disorders
Diarrhoea
|
1.7%
1/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Gastrointestinal disorders
Gastric haemorrhage
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
2.5%
2/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.2%
1/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Gastrointestinal disorders
Haematochezia
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Gastrointestinal disorders
Haemorrhoidal haemorrhage
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.2%
1/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Gastrointestinal disorders
Lower gastrointestinal haemorrhage
|
1.7%
1/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Gastrointestinal disorders
Mouth haemorrhage
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.2%
1/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Gastrointestinal disorders
Obstruction gastric
|
1.7%
1/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Gastrointestinal disorders
Pancreatitis
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
1.7%
1/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Gastrointestinal disorders
Stomatitis
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Renal and urinary disorders
Acute kidney injury
|
1.7%
1/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
4.9%
4/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Renal and urinary disorders
Renal impairment
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
2.5%
2/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Renal and urinary disorders
Urinary tract obstruction
|
1.7%
1/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Hepatobiliary disorders
Bile duct obstruction
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.2%
1/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.2%
1/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Skin and subcutaneous tissue disorders
Swelling face
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.2%
1/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
1.7%
1/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
2.1%
2/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Metabolism and nutrition disorders
Hypercreatininaemia
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.7%
1/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Metabolism and nutrition disorders
Headache
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Infections and infestations
Pneumonia
|
3.4%
2/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
9.9%
8/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
10.5%
10/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
8.3%
2/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Infections and infestations
Sepsis
|
5.2%
3/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.7%
1/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
2.5%
2/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
14.7%
14/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Infections and infestations
Lung infection
|
3.4%
2/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.7%
1/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.2%
1/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
4.2%
4/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
8.3%
2/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Infections and infestations
Bacteraemia
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.2%
1/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
4.2%
4/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
4.2%
1/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Infections and infestations
Staphylococcal infection
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.7%
1/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.2%
3/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
2.5%
2/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
2.1%
2/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Infections and infestations
Appendicitis
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Infections and infestations
Cellulitis
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Infections and infestations
Device related infection
|
1.7%
1/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Infections and infestations
Epiglottitis
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Infections and infestations
Escherichia bacteraemia
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.2%
1/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Infections and infestations
Escherichia sepsis
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.2%
1/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Infections and infestations
Infection
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.7%
1/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Infections and infestations
Localised infection
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Infections and infestations
Lower respiratory tract infection
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.2%
1/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Infections and infestations
Lung infection pseudomonal
|
1.7%
1/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Infections and infestations
Mastoiditis
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Infections and infestations
Mucormycosis
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Infections and infestations
Pharyngitis
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Infections and infestations
Pneumonia fungal
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Infections and infestations
Pseudomonal bacteraemia
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Infections and infestations
Respiratory syncytial virus infection
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Infections and infestations
Sinusitis
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Infections and infestations
Skin infection
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.2%
1/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Infections and infestations
Urosepsis
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
4.2%
1/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Infections and infestations
Viral upper respiratory tract infection
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.2%
1/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
Other adverse events
| Measure |
Diffuse Large B-cell Lymphoma (DLBCL)
n=58 participants at risk
Participants with DLBCL received Selinexor in different Schedules; Schedule 1: \<= 12 milligram per square meter (mg/m\^2) per orally (PO) alternating 3 times per week with twice weekly dosing (1 day between doses); Schedule 2: \> 12 mg/m\^2 PO 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 8: \>=40 mg/m\^2 PO twice weekly (1 day between doses) during Weeks 1 and 2; Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab intravenous (IV) once weekly for Weeks 1-4 during different cycles. Each cycle was of 28 days (Schedule 8: 21 days of cycle) or 10 scheduled selinexor doses.
|
Non-Hodgkin Lymphoma (NHL) Excluding DLBCL
n=27 participants at risk
Participants with NHL received Selinexor in different Schedules; Schedule 1: \<= 12 mg/m\^2 PO alternating 3 times per week with twice weekly dosing (1 day between doses); Schedule 2: \> 12 mg/m\^2 PO 3 times weekly for week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs 1 day apart (Schedule 3); Schedule 7: \>=45 mg/m\^2 PO once weekly (6 days between doses) to evaluate vs twice weekly (Schedules 3, 4, 5, and 6); Schedule 8: \>=40 mg/m\^2 PO twice weekly \[1 Day between doses\] during weeks 1 and 2; Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab IV once weekly for Weeks 1-4) during different cycles. Each cycle was of 28 days (Schedule 8: 21 days of cycle) or 10 scheduled selinexor doses.
|
Multiple Myeloma (MM)
n=81 participants at risk
Participants with MM received Selinexor in different Schedules; Schedule 1: \<= 12 mg/m\^2 PO alternating 3 times per week with twice weekly dosing (1 Day between doses); Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; 3 doses (36 mg/m\^2 total) in the 1-week run-in period; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 6: \>= 35 mg/m\^2 PO twice weekly with dexamethasone (20 mg twice weekly) on Days of twice weekly Selinexor dosing; Schedule 11: Group A: 40 mg; Group B: 60 mg; Group C: 80 mg twice weekly (Weeks 1, 2, and 3) at 3 fixed dose levels during different cycles. Each cycle was of 28 days or 10 scheduled selinexor doses.
|
Acute Myeloid Leukemia (AML)
n=95 participants at risk
Participants with AML received Selinexor in different Schedules; Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3), Schedule 7: \>=45 mg/m\^2 PO once weekly (6 Days between doses) to evaluate vs. twice weekly (Schedules 3, 4, 5, and 6); Schedule 8: \>=40 mg/m\^2 PO twice weekly (1 Day between doses) during Weeks 1 and 2; Schedule 10: \>= 55 mg/m\^2 PO twice weekly PO (Weeks 1 and 2) in participants with AML/18-Day treatment-free interval) during different cycles. Each cycle was of 28 days (for schedule 8: 21-day of cycle) or 10 scheduled selinexor doses.
|
Other Hematological Malignancies (ALL, CML and CLL)
n=24 participants at risk
Participants with other hematological malignancies (Acute lymphoblastic leukemia \[ALL\], Chronic myelogenous leukemia \[CML\] and chronic lymphocytic leukemia \[CLL\]) received Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly \[1 day between doses\]; Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 7: \>=45 mg/m\^2 PO once weekly (6 Days between doses) to evaluate vs. twice weekly (Schedules 3, 4, 5, and 6); Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab IV once weekly for Weeks 1-4 during different cycles. Each cycle was of 28 days or 10 scheduled selinexor doses.
|
|---|---|---|---|---|---|
|
Nervous system disorders
Dysarthria
|
5.2%
3/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.7%
1/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Eye disorders
Vision blurred
|
25.9%
15/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
14.8%
4/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
25.9%
21/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
22.1%
21/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
25.0%
6/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Vascular disorders
Hypotension
|
12.1%
7/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
18.5%
5/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
11.1%
9/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
20.0%
19/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
8.3%
2/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Vascular disorders
Hypertension
|
8.6%
5/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
7.4%
2/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.2%
1/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
9.5%
9/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
12.5%
3/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Vascular disorders
Orthostatic hypotension
|
1.7%
1/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.7%
1/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
5.3%
5/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Vascular disorders
Hot flush
|
1.7%
1/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
7.4%
2/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
General disorders
Fatigue
|
67.2%
39/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
48.1%
13/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
76.5%
62/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
70.5%
67/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
66.7%
16/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
General disorders
Pyrexia
|
36.2%
21/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
14.8%
4/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
27.2%
22/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
21.1%
20/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
4.2%
1/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
General disorders
Oedema peripheral
|
22.4%
13/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
7.4%
2/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
9.9%
8/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
22.1%
21/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
8.3%
2/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
General disorders
Asthenia
|
3.4%
2/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
14.8%
4/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
17.3%
14/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
7.4%
7/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
General disorders
Chills
|
6.9%
4/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
18.5%
5/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
8.6%
7/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
7.4%
7/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
8.3%
2/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
General disorders
Gait disturbance
|
10.3%
6/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.7%
1/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
8.6%
7/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
2.1%
2/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
8.3%
2/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
General disorders
Malaise
|
8.6%
5/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
7.4%
2/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
6.2%
5/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
2.1%
2/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
4.2%
1/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
General disorders
Non-cardiac chest pain
|
3.4%
2/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.7%
1/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
9.9%
8/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
4.2%
4/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
General disorders
Oedema
|
3.4%
2/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.2%
1/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
5.3%
5/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
4.2%
1/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
General disorders
Peripheral swelling
|
6.9%
4/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.2%
1/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Psychiatric disorders
Confusional state
|
13.8%
8/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
29.6%
8/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
18.5%
15/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
15.8%
15/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
8.3%
2/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Psychiatric disorders
Insomnia
|
13.8%
8/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
14.8%
4/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
9.9%
8/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
9.5%
9/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
8.3%
2/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Psychiatric disorders
Anxiety
|
12.1%
7/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
4.9%
4/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
7.4%
7/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Psychiatric disorders
Depression
|
5.2%
3/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
7.4%
2/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
7.4%
6/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
4.2%
4/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
4.2%
1/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Psychiatric disorders
Agitation
|
8.6%
5/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
7.4%
6/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
2.1%
2/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
8.3%
2/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Injury, poisoning and procedural complications
Fall
|
6.9%
4/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
7.4%
2/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
9.9%
8/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
8.4%
8/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
16.7%
4/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Injury, poisoning and procedural complications
Contusion
|
5.2%
3/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
7.4%
6/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
5.3%
5/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
16.7%
4/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Investigations
Weight decreased
|
24.1%
14/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
37.0%
10/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
39.5%
32/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
32.6%
31/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
12.5%
3/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Investigations
Alanine aminotransferase increased
|
12.1%
7/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
7.4%
2/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
9.9%
8/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
10.5%
10/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
8.3%
2/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Investigations
Aspartate aminotransferase increased
|
8.6%
5/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.7%
1/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
8.6%
7/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
10.5%
10/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
8.3%
2/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Investigations
Electrocardiogram QT prolonged
|
3.4%
2/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.7%
1/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.7%
3/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
10.5%
10/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
20.8%
5/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Investigations
International normalised ratio increased
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.7%
3/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
7.4%
7/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Cardiac disorders
Tachycardia
|
1.7%
1/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.7%
1/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
4.9%
4/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.2%
3/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
8.3%
2/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Cardiac disorders
Sinus tachycardia
|
6.9%
4/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.2%
1/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.2%
3/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Cardiac disorders
Palpitations
|
3.4%
2/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
7.4%
2/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.2%
1/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
4.2%
1/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
25.9%
15/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
29.6%
8/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
24.7%
20/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
33.7%
32/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
25.0%
6/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
25.9%
15/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
22.2%
6/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
22.2%
18/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
15.8%
15/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
12.5%
3/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
10.3%
6/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.7%
1/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
19.8%
16/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
24.2%
23/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
12.5%
3/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
10.3%
6/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
18.5%
5/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.2%
1/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
6.3%
6/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
1.7%
1/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
11.1%
3/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
2.5%
2/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
6.3%
6/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
6.9%
4/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.7%
3/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
2.1%
2/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
4.2%
1/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
5.2%
3/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.7%
1/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.7%
3/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
4.2%
1/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
1.7%
1/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.7%
1/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.2%
1/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
5.3%
5/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
67.2%
39/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
55.6%
15/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
64.2%
52/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
49.5%
47/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
70.8%
17/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Blood and lymphatic system disorders
Anaemia
|
58.6%
34/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
51.9%
14/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
51.9%
42/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
48.4%
46/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
66.7%
16/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Blood and lymphatic system disorders
Neutropenia
|
39.7%
23/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
44.4%
12/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
38.3%
31/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
24.2%
23/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
41.7%
10/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Blood and lymphatic system disorders
Leukopenia
|
19.0%
11/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
18.5%
5/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
13.6%
11/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
15.8%
15/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
33.3%
8/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Blood and lymphatic system disorders
Lymphopenia
|
10.3%
6/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
7.4%
2/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
8.6%
7/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
7.4%
7/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
25.0%
6/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
1.7%
1/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.7%
1/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.7%
3/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
13.7%
13/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
4.2%
1/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Blood and lymphatic system disorders
Leukocytosis
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
9.5%
9/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
12.5%
3/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Nervous system disorders
Dysgeusia
|
22.4%
13/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
22.2%
6/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
19.8%
16/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
23.2%
22/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
4.2%
1/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Nervous system disorders
Dizziness
|
24.1%
14/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
18.5%
5/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
16.0%
13/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
21.1%
20/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
20.8%
5/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Nervous system disorders
Headache
|
12.1%
7/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
14.8%
4/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
13.6%
11/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
16.8%
16/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
20.8%
5/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
3.4%
2/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
7.4%
2/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
4.9%
4/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
2.1%
2/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
16.7%
4/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Nervous system disorders
Neuropathy peripheral
|
10.3%
6/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
7.4%
2/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
2.5%
2/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.2%
3/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Nervous system disorders
Syncope
|
3.4%
2/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
7.4%
2/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
6.2%
5/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.2%
3/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Nervous system disorders
Amnesia
|
1.7%
1/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
7.4%
2/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.2%
1/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.2%
3/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Nervous system disorders
Balance disorder
|
5.2%
3/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
7.4%
2/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
2.5%
2/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Eye disorders
Cataract
|
3.4%
2/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
7.4%
2/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
7.4%
6/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.2%
3/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
4.2%
1/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Eye disorders
Visual impairment
|
8.6%
5/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.7%
1/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.7%
3/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Eye disorders
Photopsia
|
3.4%
2/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
6.2%
5/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
8.3%
2/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Eye disorders
Dry eye
|
3.4%
2/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
7.4%
2/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.2%
1/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
2.1%
2/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Eye disorders
Eye pain
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
11.1%
3/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Ear and labyrinth disorders
Hypoacusis
|
5.2%
3/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.7%
1/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
2.5%
2/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.2%
3/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Ear and labyrinth disorders
Tinnitus
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.7%
1/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.2%
1/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
5.3%
5/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Gastrointestinal disorders
Nausea
|
65.5%
38/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
66.7%
18/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
79.0%
64/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
57.9%
55/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
75.0%
18/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Gastrointestinal disorders
Vomiting
|
43.1%
25/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
40.7%
11/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
49.4%
40/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
41.1%
39/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
37.5%
9/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Gastrointestinal disorders
Diarrhoea
|
41.4%
24/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
33.3%
9/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
39.5%
32/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
48.4%
46/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
41.7%
10/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Gastrointestinal disorders
Constipation
|
25.9%
15/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
33.3%
9/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
18.5%
15/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
30.5%
29/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
25.0%
6/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Gastrointestinal disorders
Abdominal pain
|
19.0%
11/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
11.1%
3/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
11.1%
9/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
10.5%
10/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
16.7%
4/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Gastrointestinal disorders
Dyspepsia
|
13.8%
8/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
7.4%
2/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
11.1%
9/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
5.3%
5/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
4.2%
1/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Gastrointestinal disorders
Stomatitis
|
6.9%
4/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.7%
1/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.2%
1/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
17.9%
17/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
8.3%
2/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Gastrointestinal disorders
Dysphagia
|
5.2%
3/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.7%
1/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
6.2%
5/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
5.3%
5/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Gastrointestinal disorders
Dry mouth
|
3.4%
2/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
7.4%
2/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.7%
3/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
6.3%
6/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Gastrointestinal disorders
Gingival bleeding
|
1.7%
1/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.7%
1/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.7%
3/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
5.3%
5/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
2.5%
2/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
6.3%
6/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Renal and urinary disorders
Haematuria
|
5.2%
3/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.7%
1/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
6.2%
5/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
6.3%
6/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
12.5%
3/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Renal and urinary disorders
Proteinuria
|
5.2%
3/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
7.4%
2/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
4.9%
4/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.2%
3/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
16.7%
4/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Renal and urinary disorders
Urinary incontinence
|
1.7%
1/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
11.1%
3/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
2.5%
2/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
2.1%
2/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
8.3%
2/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Renal and urinary disorders
Pollakiuria
|
3.4%
2/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
2.5%
2/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
5.3%
5/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Renal and urinary disorders
Dysuria
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.2%
1/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
4.2%
4/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
8.3%
2/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Renal and urinary disorders
Urinary retention
|
5.2%
3/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
4.9%
4/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
4.2%
4/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
8.3%
2/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
10.3%
6/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
7.4%
2/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
7.4%
6/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
5.3%
5/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
12.5%
3/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
3.4%
2/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
11.1%
3/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
8.6%
7/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
2.1%
2/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
8.3%
2/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Skin and subcutaneous tissue disorders
Petechiae
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.7%
1/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
6.2%
5/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
8.4%
8/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
8.3%
2/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
3.4%
2/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
7.4%
2/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
6.2%
5/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
6.3%
6/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Skin and subcutaneous tissue disorders
Skin lesion
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
7.4%
2/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.2%
1/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.2%
3/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
20.7%
12/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
7.4%
2/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
23.5%
19/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
13.7%
13/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
4.2%
1/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
15.5%
9/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
14.8%
4/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
16.0%
13/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
15.8%
15/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
12.5%
3/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
5.2%
3/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.7%
1/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
8.6%
7/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
14.7%
14/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
16.7%
4/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
6.9%
4/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
7.4%
2/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
7.4%
6/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
6.3%
6/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
4.2%
1/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
6.9%
4/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
7.4%
2/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
6.2%
5/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
6.3%
6/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
4.2%
1/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
6.9%
4/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.7%
1/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
7.4%
6/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
4.2%
4/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
6.9%
4/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
7.4%
2/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
6.2%
5/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
4.2%
1/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
5.2%
3/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
7.4%
2/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
2.5%
2/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
2.1%
2/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.2%
1/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
5.3%
5/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Metabolism and nutrition disorders
Decreased appetite
|
58.6%
34/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
59.3%
16/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
66.7%
54/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
65.3%
62/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
54.2%
13/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
43.1%
25/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
25.9%
7/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
44.4%
36/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
35.8%
34/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
45.8%
11/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
24.1%
14/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
18.5%
5/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
14.8%
12/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
23.2%
22/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
8.3%
2/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Metabolism and nutrition disorders
Dehydration
|
12.1%
7/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
14.8%
4/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
33.3%
27/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
15.8%
15/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
4.2%
1/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Metabolism and nutrition disorders
Hypercreatininaemia
|
17.2%
10/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
28.4%
23/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
18.9%
18/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
12.5%
3/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
24.1%
14/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
14.8%
4/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
7.4%
6/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
20.0%
19/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
4.2%
1/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
13.8%
8/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
25.9%
7/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
7.4%
6/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
18.9%
18/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
12.5%
3/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
6.9%
4/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
22.2%
6/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
8.6%
7/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
18.9%
18/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
12.5%
3/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
10.3%
6/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
14.8%
4/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
7.4%
6/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
13.7%
13/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
4.2%
1/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
6.9%
4/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
11.1%
3/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.7%
3/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
11.6%
11/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
4.2%
1/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
3.4%
2/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
14.8%
4/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
6.2%
5/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
9.5%
9/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
4.2%
1/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
8.6%
5/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.7%
1/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.2%
1/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
10.5%
10/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
4.2%
1/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Metabolism and nutrition disorders
Hyperamylasaemia
|
8.6%
5/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.7%
3/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
6.3%
6/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Metabolism and nutrition disorders
Hyperlipasaemia
|
3.4%
2/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
7.4%
6/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
5.3%
5/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Metabolism and nutrition disorders
Hypermagnesaemia
|
5.2%
3/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
7.4%
2/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.2%
1/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
2.1%
2/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.7%
1/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.7%
3/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
1.1%
1/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
8.3%
2/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Infections and infestations
Urinary tract infection
|
8.6%
5/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
11.1%
3/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
8.6%
7/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
5.3%
5/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
16.7%
4/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Infections and infestations
Upper respiratory tract infection
|
3.4%
2/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
7.4%
2/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
11.1%
9/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
4.2%
4/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
4.2%
1/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Infections and infestations
Lung infection
|
8.6%
5/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
7.4%
2/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.7%
3/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
3.2%
3/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
4.2%
1/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Infections and infestations
Pneumonia
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
4.9%
4/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
9.5%
9/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
4.2%
1/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
|
Infections and infestations
Oral infection
|
0.00%
0/58 • From first dose of study drug administration to end of treatment (up to 27 months)
|
7.4%
2/27 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/81 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/95 • From first dose of study drug administration to end of treatment (up to 27 months)
|
0.00%
0/24 • From first dose of study drug administration to end of treatment (up to 27 months)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place