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Safety Study of the Selective Inhibitor of Nuclear Export (SINE) KPT-330 in Patients With Advanced Hematological Cancer

Sponsor
Karyopharm Therapeutics Inc (Industry)
Overall Status
Completed
CT.gov ID
NCT01607892
Collaborator
(none)
286
Enrollment
12
Locations
1
Arm
38.7
Actual Duration (Months)
23.8
Patients Per Site
0.6
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this research study is to find out more information relating to the highest dose of KCP-330 that can be given safely and side effects it may cause, to examine how the body affects KCP-330 concentrations in the blood (pharmacokinetics or PK), to examine the effects of KCP-330 on the body (pharmacodynamics or PDn) and to obtain information on its effectiveness in treating cancer.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
286 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase I Study of the Safety, Pharmacokinetics and Pharmacodynamics of Escalating Doses of the Selective Inhibitor of Nuclear Export/SINE™ Compound KPT-330 in Patients With Advanced Hematological Malignancies
Actual Study Start Date :
Jul 23, 2012
Actual Primary Completion Date :
Oct 13, 2015
Actual Study Completion Date :
Oct 13, 2015

Arms and Interventions

Arm Intervention/Treatment
Experimental: selinexor

Drug: KPT-330
Other Names:
  • Selinexor

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) [From first dose of study drug administration to end of treatment (up to 27 months)]

      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.

    2. Recommended Phase 2 Dose (RP2D) of Selinexor [From first dose of study drug administration to end of treatment (up to 27 months)]

      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.

    Secondary Outcome Measures

    1. Maximum Observed Plasma Concentration (Cmax) of Selinexor [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 2]

      Cmax was defined as the maximum observed concentration, taken directly from the plasma concentration.

    2. Time to Maximum Observed Concentration (Tmax) of Selinexor [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 2]

      Tmax was defined as time of first observation of Cmax, taken directly from the plasma concentration data.

    3. Average Concentration From Time 0 to 24 Hours (Cavg0-24h) of Selinexor [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 2]

      Cavg0-24h was defined as average concentration from time 0 to 24 hours.

    4. Area Under the Concentration-Time Curve From Time 0 to t (AUC0-t) of Selinexor [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 2]

      AUC0-t was defined as area under the concentration-time curve from time zero to the last non-zero concentration.

    5. Area Under the Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Selinexor [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 2]

      AUC0-inf was defined as the area under the concentration-time curve from time zero to infinity (extrapolated).

    6. Apparent Volume of Distribution Uncorrected for Fraction Absorbed (Vd/F) of Selinexor [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 2]

      Apparent volume of distribution was calculated as Dose/ (kel *AUC0-inf), uncorrected for fraction absorbed, reported normalized by participant body weight (kilogram [kg]).

    7. Apparent Total Body Clearance, Uncorrected for Fraction Absorbed (Cl/F) of Selinexor [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 2]

      Cl/F was calculated as Dose/AUC0-inf, uncorrected for fraction absorbed, reported normalized by participant body weight (kg).

    8. Terminal Half-Life (t½) of Selinexor [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 2]

      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.

    9. Number of Participants With Overall Response of Selinexor [From first dose of study drug administration to end of treatment (up to 27 months)]

      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).

    10. Duration of Response [From first dose of study drug administration to end of treatment (up to 27 months)]

      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.

    11. Progression-free Survival [Cycle 1 Day 1 to End of Treatment (up to 27 months)]

      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.

    12. Duration of at Least Stable Disease [Cycle 1 Day 1 to End of Treatment (up to 27 months)]

      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.

    13. Overall Survival [Cycle 1 Day 1 to End of Treatment (up to 27 months)]

      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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    Inclusion Criteria

    1. Malignancies that are refractory to or intolerant of established therapy known to provide clinical benefit. Patients must not be candidates for anti-tumor regimes known to provide clinical benefit.

    2. All patients must have evidence of progressive disease on study entry. Previously untreated patients who are not chemotherapy candidates on Arm 2 may have advanced disease (without clear progression). There is no upper limit on the number of prior treatments provided that all inclusion criteria are met, and exclusion criteria are not met.

    Exclusion Criteria

    1. Radiation, chemotherapy, or immunotherapy or any other anticancer therapy ≤2 weeks prior to cycle 1 day 1 and mitomycin C and radioimmunotherapy 6 weeks prior to cycle 1 day 1.

    2. Patients with active graft versus host disease after allogeneic stem cell transplantation. At least 3 months must have elapsed since completion of allogeneic stem cell transplantation except for patients with AML, where at least 2 months must have elapsed;

    3. Known active hepatitis A, B, or C infection; or known to be positive for HCV RNA or HBsAg (HBV surface antigen);

    4. Patients with active CNS malignancy. Asymptomatic small lesions are not considered active. Treated lesions may be considered inactive if they are stable for at least 3 months. Patient with malignant cells in their cerebrospinal fluid (CSF) without CNS symptom may be included.

    5. Significantly diseased or obstructed gastrointestinal tract or uncontrolled vomiting or diarrhea.

    6. Grade ≥2 peripheral neuropathy at baseline (within 14 days prior to cycle 1 day 1).

    7. Macular degeneration, uncontrolled glaucoma, or markedly decreased visual acuity.

    8. In the opinion of the investigator, patients who are significantly below their ideal body weight.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Moffitt Cancer Center Tampa Florida United States 33612
    2 Dana-Farber Cancer Institute Boston Massachusetts United States 02215
    3 Washington University School of Medicine Saint Louis Missouri United States 63110
    4 Hackensack University Medical Center Hackensack New Jersey United States 07601
    5 Weill Cornell Medical Center New York New York United States 10065
    6 Gabrail Cancer Center Research Canton Ohio United States 44718
    7 The Ohio State University Columbus Ohio United States 43210
    8 Sarah Cannon Research Institute Nashville Tennessee United States 37203
    9 MD Anderson Cancer Center Houston Texas United States 77030
    10 Tom Baker Cancer Centre Calgary Alberta Canada T2W 4N2
    11 Princess Margaret Hospital Toronto Ontario Canada M5T 2M9
    12 Rigshospitalet Copenhagen Denmark 2100

    Sponsors and Collaborators

    • Karyopharm Therapeutics Inc

    Investigators

    • Study Director: Michael Kauffman, MD, Ph.D, Karyopharm Therapeutics Inc

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Karyopharm Therapeutics Inc
    ClinicalTrials.gov Identifier:
    NCT01607892
    Other Study ID Numbers:
    • KCP-330-001
    First Posted:
    May 30, 2012
    Last Update Posted:
    Apr 1, 2021
    Last Verified:
    Mar 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Karyopharm Therapeutics Inc
    Selinexor
    KPT-330
    Multiple Myeloma
    non-Hodgkin Lymphoma
    Chronic Lymphocytic Leukemia
    Waldenström's macroglobulinemia
    Peripheral T-Cell Lymphoma
    Cutaneous T-Cell Lymphoma
    Chronic Myelocytic Leukemia
    Acute Lymphoblastic Leukemia
    Additional relevant MeSH terms:
    Neoplasms
    Hematologic Neoplasms

    Study Results

    Participant Flow

    Recruitment Details 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).
    Pre-assignment Detail 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).
    Arm/Group Title Diffuse Large B-cell Lymphoma (DLBCL) Non-Hodgkin Lymphoma (NHL) Excluding DLBCL Multiple Myeloma (MM) Acute Myeloid Leukemia (AML) Other Hematological Malignancies (ALL, CML and CLL)
    Arm/Group Description 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. 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. 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. 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. 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.
    Period Title: Overall Study
    STARTED 58 27 81 95 24
    COMPLETED 0 0 0 0 0
    NOT COMPLETED 58 27 81 95 24

    Baseline Characteristics

    Arm/Group Title Diffuse Large B-cell Lymphoma (DLBCL) Non-Hodgkin Lymphoma (NHL) Excluding DLBCL Multiple Myeloma (MM) Acute Myeloid Leukemia (AML) Other Hematological Malignancies (ALL, CML and CLL) Total
    Arm/Group Description 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. 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. 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. 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. 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 of all reporting groups
    Overall Participants 58 27 81 95 24 285
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    57.8
    (14.00)
    58.0
    (15.90)
    62.1
    (8.76)
    65.6
    (15.33)
    60.9
    (15.23)
    61.9
    (13.79)
    Sex: Female, Male (Count of Participants)
    Female
    28
    48.3%
    9
    33.3%
    38
    46.9%
    40
    42.1%
    8
    33.3%
    123
    43.2%
    Male
    30
    51.7%
    18
    66.7%
    43
    53.1%
    55
    57.9%
    16
    66.7%
    162
    56.8%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    2
    3.4%
    1
    3.7%
    4
    4.9%
    2
    2.1%
    0
    0%
    9
    3.2%
    Not Hispanic or Latino
    52
    89.7%
    23
    85.2%
    72
    88.9%
    88
    92.6%
    23
    95.8%
    258
    90.5%
    Unknown or Not Reported
    4
    6.9%
    3
    11.1%
    5
    6.2%
    5
    5.3%
    1
    4.2%
    18
    6.3%
    Race/Ethnicity, Customized (Count of Participants)
    White
    52
    89.7%
    20
    74.1%
    65
    80.2%
    88
    92.6%
    23
    95.8%
    248
    87%
    Black
    2
    3.4%
    3
    11.1%
    11
    13.6%
    5
    5.3%
    1
    4.2%
    22
    7.7%
    Asian
    0
    0%
    1
    3.7%
    4
    4.9%
    1
    1.1%
    1
    4.2%
    7
    2.5%
    Native Hawaiian or Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    American Indian or Alaskan Native
    0
    0%
    1
    3.7%
    0
    0%
    0
    0%
    0
    0%
    1
    0.4%
    Other
    0
    0%
    2
    7.4%
    1
    1.2%
    0
    0%
    0
    0%
    3
    1.1%
    Unknown/Not Reported
    4
    6.9%
    0
    0%
    0
    0%
    1
    1.1%
    0
    0%
    5
    1.8%

    Outcome Measures

    1. Primary Outcome
    Title Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
    Description 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.
    Time Frame From first dose of study drug administration to end of treatment (up to 27 months)

    Outcome Measure Data

    Analysis Population Description
    Safety population consisted of all participants who received at least 1 dose of selinexor.
    Arm/Group Title Diffuse Large B-cell Lymphoma (DLBCL) Non-Hodgkin Lymphoma (NHL) Excluding DLBCL Multiple Myeloma (MM) Acute Myeloid Leukemia (AML) Other Hematological Malignancies (ALL, CML and CLL)
    Arm/Group Description 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. 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. 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. 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. 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.
    Measure Participants 58 27 81 95 24
    At Least One TEAE
    58
    100%
    27
    100%
    81
    100%
    95
    100%
    24
    100%
    At Least One Serious TEAE
    33
    56.9%
    7
    25.9%
    52
    64.2%
    73
    76.8%
    13
    54.2%
    2. Primary Outcome
    Title Recommended Phase 2 Dose (RP2D) of Selinexor
    Description 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.
    Time Frame From first dose of study drug administration to end of treatment (up to 27 months)

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Advanced Hematological Malignancies.
    Arm/Group Description Participants received selinexor doses of <= 12 mg/m^2, post oral for all cycles 3 times weekly for Weeks 1 and 3 in schedule 1; >12 mg/m^2 3 times weekly for Weeks 2 and 4 in schedule 2; >=30 mg/m^2 on Day 1 and 3 in schedule 3; >= 23 mg/m^2 on Day 1 and Day 2 for a 28-day cycle in schedule 4; >= 30 mg/m^2 on Day 1 and 4 in schedule 5; >= 35 mg/m^2 combined with dexamethasone 20 mg on Day 1 and 3 in schedule 6; >= 45 mg/m^2 once-weekly in schedule 7; >= 40 mg/m^2 twice-weekly for first 2 weeks on Days 1, 3, 8, and 10 followed by an 11-day treatment-free interval in schedule 8; >= 30 mg/m^2 twice weekly for 3 weeks in 28-day cycle followed by fixed dose of 375 mg/m^2 Rituximab in schedule 9; 55 mg/m^2 twice-weekly on Days 1, 3, 8, and 10 followed by 18-day treatment-free interval in schedule 10; 40, 60, 80 mg (group A, group B, group C) twice weekly during the first 3 weeks, on Days 1, 3, 8, 10, 15 and 17 followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 11.
    Measure Participants 285
    Number [milligram per square meter (mg/m^2)]
    35
    3. Secondary Outcome
    Title Maximum Observed Plasma Concentration (Cmax) of Selinexor
    Description Cmax was defined as the maximum observed concentration, taken directly from the plasma concentration.
    Time Frame 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 2

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Selinexor (3 mg/m^2) Selinexor (6 mg/m^2) Selinexor (12 mg/m^2) Selinexor (16.8 mg/m^2) Selinexor (23 mg/m^2) Selinexor (30 mg/m^2) Selinexor (35 mg/m^2) Selinexor (40 mg/m^2) Selinexor (46 mg/m^2) Selinexor (55 mg/m^2) Selinexor (60 mg/m^2) Selinexor (70 mg/m^2) Selinexor (80 mg/m^2)
    Arm/Group Description Participants received selinexor dose of 3 mg/m^2 orally at Cycle 1, on Day 1, 3, 5, 8, 10, 15, 17, 19, 22 and 24 in schedule 1. Participants received selinexor dose of 6 mg/m^2 orally at Cycle 1, on Day 1, 3, 5, 8, 10, 15, 17, 19, 22 and 24 in schedule 1. Participants received selinexor dose of 12 mg/m^2 orally at Cycle 1, on Day 1, 3, 5, 8, 10, 15, 17, 19, 22 and 24 in schedule 1. Participants received selinexor dose of 16.8 mg/m^2 orally at Cycle 1, on Day 1, 3, 5, 8, 15, 17, 19, and 22 in schedule 2. Participants received selinexor dose of 23 mg/m^2 orally at Cycle 1, on Day 1 and 2 of each week for a 28-day cycle in schedule 4. 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. Participants received selinexor dose of 35 mg/m^2 orally at Cycle 1, on Day 1 and 3 in schedule 6. 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. Participants received selinexor dose of 46 mg/m^2 orally at Cycle 1, on Day 1 once-weekly in schedule 7. 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. 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. 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. 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.
    Measure Participants 2 3 6 13 18 21 13 8 9 8 4 8 5
    Geometric Mean (Geometric Coefficient of Variation) [nanogram per milliliter (ng/mL)]
    49.0
    (NA)
    50.0
    (61.1)
    149
    (37.6)
    205
    (46.8)
    262
    (37.5)
    387
    (37.1)
    407
    (44.4)
    416
    (36.6)
    670
    (18.5)
    583
    (41.4)
    668
    (33.2)
    800
    (32.4)
    1068
    (49.3)
    4. Secondary Outcome
    Title Time to Maximum Observed Concentration (Tmax) of Selinexor
    Description Tmax was defined as time of first observation of Cmax, taken directly from the plasma concentration data.
    Time Frame 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 2

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Selinexor (3 mg/m^2) Selinexor (6 mg/m^2) Selinexor (12 mg/m^2) Selinexor (16.8 mg/m^2) Selinexor (23 mg/m^2) Selinexor (30 mg/m^2) Selinexor (35 mg/m^2) Selinexor (40 mg/m^2) Selinexor (46 mg/m^2) Selinexor (55 mg/m^2) Selinexor (60 mg/m^2) Selinexor (70 mg/m^2) Selinexor (80 mg/m^2)
    Arm/Group Description Participants received selinexor dose of 3 mg/m^2 orally at Cycle 1, on Day 1, 3, 5, 8, 10, 15, 17, 19, 22 and 24 in schedule 1. Participants received selinexor dose of 6 mg/m^2 orally at Cycle 1, on Day 1, 3, 5, 8, 10, 15, 17, 19, 22 and 24 in schedule 1. Participants received selinexor dose of 12 mg/m^2 orally at Cycle 1, on Day 1, 3, 5, 8, 10, 15, 17, 19, 22 and 24 in schedule 1. Participants received selinexor dose of 16.8 mg/m^2 orally at Cycle 1, on Day 1, 3, 5, 8, 15, 17, 19, and 22 in schedule 2. Participants received selinexor dose of 23 mg/m^2 orally at Cycle 1, on Day 1 and 2 of each week for a 28-day cycle in schedule 4. 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. Participants received selinexor dose of 35 mg/m^2 orally at Cycle 1, on Day 1 and 3 in schedule 6. 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. Participants received selinexor dose of 46 mg/m^2 orally at Cycle 1, on Day 1 once-weekly in schedule 7. 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. 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. 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. 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.
    Measure Participants 2 3 6 13 18 21 13 8 9 8 4 8 5
    Median (Full Range) [hour]
    NA
    4.0
    3.0
    2.08
    2.0
    2.0
    2.0
    4.0
    2.0
    2.9
    1.9
    2.0
    2.0
    5. Secondary Outcome
    Title Average Concentration From Time 0 to 24 Hours (Cavg0-24h) of Selinexor
    Description Cavg0-24h was defined as average concentration from time 0 to 24 hours.
    Time Frame 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 2

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Selinexor (3 mg/m^2) Selinexor (6 mg/m^2) Selinexor (12 mg/m^2) Selinexor (16.8 mg/m^2) Selinexor (23 mg/m^2) Selinexor (30 mg/m^2) Selinexor (35 mg/m^2) Selinexor (40 mg/m^2) Selinexor (46 mg/m^2) Selinexor (55 mg/m^2) Selinexor (60 mg/m^2) Selinexor (70 mg/m^2) Selinexor (80 mg/m^2)
    Arm/Group Description Participants received selinexor dose of 3 mg/m^2 orally at Cycle 1, on Day 1, 3, 5, 8, 10, 15, 17, 19, 22 and 24 in schedule 1. Participants received selinexor dose of 6 mg/m^2 orally at Cycle 1, on Day 1, 3, 5, 8, 10, 15, 17, 19, 22 and 24 in schedule 1. Participants received selinexor dose of 12 mg/m^2 orally at Cycle 1, on Day 1, 3, 5, 8, 10, 15, 17, 19, 22 and 24 in schedule 1. Participants received selinexor dose of 16.8 mg/m^2 orally at Cycle 1, on Day 1, 3, 5, 8, 15, 17, 19, and 22 in schedule 2. Participants received selinexor dose of 23 mg/m^2 orally at Cycle 1, on Day 1 and 2 of each week for a 28-day cycle in schedule 4. 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. Participants received selinexor dose of 35 mg/m^2 orally at Cycle 1, on Day 1 and 3 in schedule 6. 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. Participants received selinexor dose of 46 mg/m^2 orally at Cycle 1, on Day 1 once-weekly in schedule 7. 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. 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. 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. 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.
    Measure Participants 2 3 6 12 17 19 13 8 9 6 3 4 1
    Geometric Mean (Geometric Coefficient of Variation) [ng/mL]
    17.0
    (NA)
    20.3
    (94.8)
    61.8
    (39.9)
    79.0
    (61.8)
    108
    (46.8)
    160
    (38.0)
    168
    (54.0)
    163
    (29.2)
    297
    (26.3)
    208
    (19.1)
    337
    (4.2)
    353
    (26.2)
    NA
    (NA)
    6. Secondary Outcome
    Title Area Under the Concentration-Time Curve From Time 0 to t (AUC0-t) of Selinexor
    Description AUC0-t was defined as area under the concentration-time curve from time zero to the last non-zero concentration.
    Time Frame 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 2

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Selinexor (3 mg/m^2) Selinexor (6 mg/m^2) Selinexor (12 mg/m^2) Selinexor (16.8 mg/m^2) Selinexor (23 mg/m^2) Selinexor (30 mg/m^2) Selinexor (35 mg/m^2) Selinexor (40 mg/m^2) Selinexor (46 mg/m^2) Selinexor (55 mg/m^2) Selinexor (60 mg/m^2) Selinexor (70 mg/m^2) Selinexor (80 mg/m^2)
    Arm/Group Description Participants received selinexor dose of 3 mg/m^2 orally at Cycle 1, on Day 1, 3, 5, 8, 10, 15, 17, 19, 22 and 24 in schedule 1. Participants received selinexor dose of 6 mg/m^2 orally at Cycle 1, on Day 1, 3, 5, 8, 10, 15, 17, 19, 22 and 24 in schedule 1. Participants received selinexor dose of 12 mg/m^2 orally at Cycle 1, on Day 1, 3, 5, 8, 10, 15, 17, 19, 22 and 24 in schedule 1. Participants received selinexor dose of 16.8 mg/m^2 orally at Cycle 1, on Day 1, 3, 5, 8, 15, 17, 19, and 22 in schedule 2. Participants received selinexor dose of 23 mg/m^2 orally at Cycle 1, on Day 1 and 2 of each week for a 28-day cycle in schedule 4. 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. Participants received selinexor dose of 35 mg/m^2 orally at Cycle 1, on Day 1 and 3 in schedule 6. 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. Participants received selinexor dose of 46 mg/m^2 orally at Cycle 1, on Day 1 once-weekly in schedule 7. 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. 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. 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. 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.
    Measure Participants 2 3 6 13 18 21 13 8 9 8 4 8 5
    Geometric Mean (Geometric Coefficient of Variation) [nanogram* hours per milliliter]
    331
    (NA)
    564
    (41.9)
    1459
    (20.5)
    1829
    (23.3)
    2774
    (36.7)
    3461
    (26.9)
    3901
    (29.2)
    4481
    (23.8)
    5228
    (21.6)
    5601
    (36.2)
    5282
    (57.9)
    5466
    (45.7)
    5544
    (33.2)
    7. Secondary Outcome
    Title Area Under the Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Selinexor
    Description AUC0-inf was defined as the area under the concentration-time curve from time zero to infinity (extrapolated).
    Time Frame 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 2

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Selinexor (3 mg/m^2) Selinexor (6 mg/m^2) Selinexor (12 mg/m^2) Selinexor (16.8 mg/m^2) Selinexor (23 mg/m^2) Selinexor (30 mg/m^2) Selinexor (35 mg/m^2) Selinexor (40 mg/m^2) Selinexor (46 mg/m^2) Selinexor (55 mg/m^2) Selinexor (60 mg/m^2) Selinexor (70 mg/m^2) Selinexor (80 mg/m^2)
    Arm/Group Description Participants received selinexor dose of 3 mg/m^2 orally at Cycle 1, on Day 1, 3, 5, 8, 10, 15, 17, 19, 22 and 24 in schedule 1. Participants received selinexor dose of 6 mg/m^2 orally at Cycle 1, on Day 1, 3, 5, 8, 10, 15, 17, 19, 22 and 24 in schedule 1. Participants received selinexor dose of 12 mg/m^2 orally at Cycle 1, on Day 1, 3, 5, 8, 10, 15, 17, 19, 22 and 24 in schedule 1. Participants received selinexor dose of 16.8 mg/m^2 orally at Cycle 1, on Day 1, 3, 5, 8, 15, 17, 19, and 22 in schedule 2. Participants received selinexor dose of 23 mg/m^2 orally at Cycle 1, on Day 1 and 2 of each week for a 28-day cycle in schedule 4. 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. Participants received selinexor dose of 35 mg/m^2 orally at Cycle 1, on Day 1 and 3 in schedule 6. 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. Participants received selinexor dose of 46 mg/m^2 orally at Cycle 1, on Day 1 once-weekly in schedule 7. 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. 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. 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. 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.
    Measure Participants 2 2 6 12 12 21 13 8 9 7 3 4 1
    Geometric Mean (Geometric Coefficient of Variation) [ng*h/mL]
    348
    (NA)
    733
    (NA)
    1529
    (18.7)
    1867
    (23.6)
    2645
    (1111)
    3513
    (26.0)
    3948
    (28.6)
    4552
    (23.7)
    5284
    (21.0)
    6089
    (32.3)
    6964
    (12.2)
    7803
    (8.5)
    NA
    (NA)
    8. Secondary Outcome
    Title Apparent Volume of Distribution Uncorrected for Fraction Absorbed (Vd/F) of Selinexor
    Description Apparent volume of distribution was calculated as Dose/ (kel *AUC0-inf), uncorrected for fraction absorbed, reported normalized by participant body weight (kilogram [kg]).
    Time Frame 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 2

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Selinexor (3 mg/m^2) Selinexor (6 mg/m^2) Selinexor (12 mg/m^2) Selinexor (16.8 mg/m^2) Selinexor (23 mg/m^2) Selinexor (30 mg/m^2) Selinexor (35 mg/m^2) Selinexor (40 mg/m^2) Selinexor (46 mg/m^2) Selinexor (55 mg/m^2) Selinexor (60 mg/m^2) Selinexor (70 mg/m^2) Selinexor (80 mg/m^2)
    Arm/Group Description Participants received selinexor dose of 3 mg/m^2 orally at Cycle 1, on Day 1, 3, 5, 8, 10, 15, 17, 19, 22 and 24 in schedule 1. Participants received selinexor dose of 6 mg/m^2 orally at Cycle 1, on Day 1, 3, 5, 8, 10, 15, 17, 19, 22 and 24 in schedule 1. Participants received selinexor dose of 12 mg/m^2 orally at Cycle 1, on Day 1, 3, 5, 8, 10, 15, 17, 19, 22 and 24 in schedule 1. Participants received selinexor dose of 16.8 mg/m^2 orally at Cycle 1, on Day 1, 3, 5, 8, 15, 17, 19, and 22 in schedule 2. Participants received selinexor dose of 23 mg/m^2 orally at Cycle 1, on Day 1 and 2 of each week for a 28-day cycle in schedule 4. 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. Participants received selinexor dose of 35 mg/m^2 orally at Cycle 1, on Day 1 and 3 in schedule 6. 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. Participants received selinexor dose of 46 mg/m^2 orally at Cycle 1, on Day 1 once-weekly in schedule 7. 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. 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. 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. 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.
    Measure Participants 2 2 6 12 12 21 13 8 9 7 3 4 1
    Geometric Mean (Geometric Coefficient of Variation) [Liter per kilogram (L/kg)]
    1.6
    (NA)
    1.5
    (NA)
    1.9
    (21.2)
    1.9
    (29.9)
    1.9
    (34.1)
    1.7
    (24.1)
    2.0
    (30.3)
    1.7
    (29.1)
    1.8
    (12.9)
    1.9
    (27.9)
    1.6
    (23.0)
    1.7
    (13.4)
    NA
    (NA)
    9. Secondary Outcome
    Title Apparent Total Body Clearance, Uncorrected for Fraction Absorbed (Cl/F) of Selinexor
    Description Cl/F was calculated as Dose/AUC0-inf, uncorrected for fraction absorbed, reported normalized by participant body weight (kg).
    Time Frame 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 2

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Selinexor (3 mg/m^2) Selinexor (6 mg/m^2) Selinexor (12 mg/m^2) Selinexor (16.8 mg/m^2) Selinexor (23 mg/m^2) Selinexor (30 mg/m^2) Selinexor (35 mg/m^2) Selinexor (40 mg/m^2) Selinexor (46 mg/m^2) Selinexor (55 mg/m^2) Selinexor (60 mg/m^2) Selinexor (70 mg/m^2) Selinexor (80 mg/m^2)
    Arm/Group Description Participants received selinexor dose of 3 mg/m^2 orally at Cycle 1, on Day 1, 3, 5, 8, 10, 15, 17, 19, 22 and 24 in schedule 1. Participants received selinexor dose of 6 mg/m^2 orally at Cycle 1, on Day 1, 3, 5, 8, 10, 15, 17, 19, 22 and 24 in schedule 1. Participants received selinexor dose of 12 mg/m^2 orally at Cycle 1, on Day 1, 3, 5, 8, 10, 15, 17, 19, 22 and 24 in schedule 1. Participants received selinexor dose of 16.8 mg/m^2 orally at Cycle 1, on Day 1, 3, 5, 8, 15, 17, 19, and 22 in schedule 2. Participants received selinexor dose of 23 mg/m^2 orally at Cycle 1, on Day 1 and 2 of each week for a 28-day cycle in schedule 4. 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. Participants received selinexor dose of 35 mg/m^2 orally at Cycle 1, on Day 1 and 3 in schedule 6. 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. Participants received selinexor dose of 46 mg/m^2 orally at Cycle 1, on Day 1 once-weekly in schedule 7. 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. 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. 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. 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.
    Measure Participants 2 2 6 12 12 21 13 8 9 7 3 4 1
    Geometric Mean (Geometric Coefficient of Variation) [Liter per hour per kilogram (L/h/kg)]
    0.19
    (NA)
    0.21
    (NA)
    0.21
    (26.6)
    0.22
    (22.8)
    0.20
    (54.9)
    0.21
    (25.3)
    0.22
    (25.9)
    0.23
    (26.2)
    0.22
    (12.9)
    0.20
    (24.6)
    0.19
    (27.5)
    0.22
    (7.8)
    NA
    (NA)
    10. Secondary Outcome
    Title Terminal Half-Life (t½) of Selinexor
    Description 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.
    Time Frame 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 2

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Selinexor (3 mg/m^2) Selinexor (6 mg/m^2) Selinexor (12 mg/m^2) Selinexor (16.8 mg/m^2) Selinexor (23 mg/m^2) Selinexor (30 mg/m^2) Selinexor (35 mg/m^2) Selinexor (40 mg/m^2) Selinexor (46 mg/m^2) Selinexor (55 mg/m^2) Selinexor (60 mg/m^2) Selinexor (70 mg/m^2) Selinexor (80 mg/m^2)
    Arm/Group Description Participants received selinexor dose of 3 mg/m^2 orally at Cycle 1, on Day 1, 3, 5, 8, 10, 15, 17, 19, 22 and 24 in schedule 1. Participants received selinexor dose of 6 mg/m^2 orally at Cycle 1, on Day 1, 3, 5, 8, 10, 15, 17, 19, 22 and 24 in schedule 1. Participants received selinexor dose of 12 mg/m^2 orally at Cycle 1, on Day 1, 3, 5, 8, 10, 15, 17, 19, 22 and 24 in schedule 1. Participants received selinexor dose of 16.8 mg/m^2 orally at Cycle 1, on Day 1, 3, 5, 8, 15, 17, 19, and 22 in schedule 2. Participants received selinexor dose of 23 mg/m^2 orally at Cycle 1, on Day 1 and 2 of each week for a 28-day cycle in schedule 4. 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. Participants received selinexor dose of 35 mg/m^2 orally at Cycle 1, on Day 1 and 3 in schedule 6. 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. Participants received selinexor dose of 46 mg/m^2 orally at Cycle 1, on Day 1 once-weekly in schedule 7. 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. 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. 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. 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.
    Measure Participants 2 2 6 12 12 21 13 8 9 7 3 4 1
    Median (Full Range) [hour]
    NA
    NA
    6.2
    6.1
    6.9
    5.8
    6.2
    4.8
    5.7
    6.6
    5.9
    5.2
    NA
    11. Secondary Outcome
    Title Number of Participants With Overall Response of Selinexor
    Description 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).
    Time Frame From first dose of study drug administration to end of treatment (up to 27 months)

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Diffuse Large B-cell Lymphoma (DLBCL) Non-Hodgkin Lymphoma (NHL) Excluding DLBCL Multiple Myeloma (MM) Acute Myeloid Leukemia (AML) Other Hematological Malignancies (ALL, CML and CLL)
    Arm/Group Description 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. 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. 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. 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. 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.
    Measure Participants 58 27 81 95 24
    Complete response
    5
    8.6%
    1
    3.7%
    0
    0%
    0
    0%
    0
    0%
    Partial response
    7
    12.1%
    8
    29.6%
    6
    7.4%
    0
    0%
    0
    0%
    Morphologic complete remission
    0
    0%
    0
    0%
    0
    0%
    4
    4.2%
    0
    0%
    Partial remission
    0
    0%
    0
    0%
    0
    0%
    3
    3.2%
    1
    4.2%
    Complete cytogenetic response
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Complete hematological response
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    12. Secondary Outcome
    Title Duration of Response
    Description 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.
    Time Frame From first dose of study drug administration to end of treatment (up to 27 months)

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Diffuse Large B-cell Lymphoma (DLBCL) Non-Hodgkin Lymphoma (NHL) Excluding DLBCL Multiple Myeloma (MM) Acute Myeloid Leukemia (AML) Other Hematological Malignancies (ALL, CML and CLL)
    Arm/Group Description 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. 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. 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. 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. 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.
    Measure Participants 12 9 7 11 1
    Median (95% Confidence Interval) [Days]
    335.5
    251
    180
    76
    NA
    13. Secondary Outcome
    Title Progression-free Survival
    Description 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.
    Time Frame Cycle 1 Day 1 to End of Treatment (up to 27 months)

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Diffuse Large B-cell Lymphoma (DLBCL) Non-Hodgkin Lymphoma (NHL) Excluding DLBCL Multiple Myeloma (MM) Acute Myeloid Leukemia (AML) Other Hematological Malignancies (ALL, CML and CLL)
    Arm/Group Description 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. 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. 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. 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. 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.
    Measure Participants 58 27 81 95 24
    Median (95% Confidence Interval) [Days]
    47
    110
    57
    44
    57
    14. Secondary Outcome
    Title Duration of at Least Stable Disease
    Description 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.
    Time Frame Cycle 1 Day 1 to End of Treatment (up to 27 months)

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Diffuse Large B-cell Lymphoma (DLBCL) Non-Hodgkin Lymphoma (NHL) Excluding DLBCL Multiple Myeloma (MM) Acute Myeloid Leukemia (AML) Other Hematological Malignancies (ALL, CML and CLL)
    Arm/Group Description 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. 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. 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. 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. 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.
    Measure Participants 58 27 81 95 24
    Median (95% Confidence Interval) [Days]
    52
    114
    57
    80
    64
    15. Secondary Outcome
    Title Overall Survival
    Description 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.
    Time Frame Cycle 1 Day 1 to End of Treatment (up to 27 months)

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Diffuse Large B-cell Lymphoma (DLBCL) Non-Hodgkin Lymphoma (NHL) Excluding DLBCL Multiple Myeloma (MM) Acute Myeloid Leukemia (AML) Other Hematological Malignancies (ALL, CML and CLL)
    Arm/Group Description 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. 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. 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. 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. 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.
    Measure Participants 58 27 81 95 24
    Median (95% Confidence Interval) [Days]
    138
    423
    366
    76
    82

    Adverse Events

    Time Frame From first dose of study drug administration to end of treatment (up to 27 months)
    Adverse Event Reporting Description
    Arm/Group Title Diffuse Large B-cell Lymphoma (DLBCL) Non-Hodgkin Lymphoma (NHL) Excluding DLBCL Multiple Myeloma (MM) Acute Myeloid Leukemia (AML) Other Hematological Malignancies (ALL, CML and CLL)
    Arm/Group Description 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. 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. 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. 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. 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.
    All Cause Mortality
    Diffuse Large B-cell Lymphoma (DLBCL) Non-Hodgkin Lymphoma (NHL) Excluding DLBCL Multiple Myeloma (MM) Acute Myeloid Leukemia (AML) Other Hematological Malignancies (ALL, CML and CLL)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Diffuse Large B-cell Lymphoma (DLBCL) Non-Hodgkin Lymphoma (NHL) Excluding DLBCL Multiple Myeloma (MM) Acute Myeloid Leukemia (AML) Other Hematological Malignancies (ALL, CML and CLL)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 33/58 (56.9%) 7/27 (25.9%) 52/81 (64.2%) 73/95 (76.8%) 13/24 (54.2%)
    Blood and lymphatic system disorders
    Febrile neutropenia 4/58 (6.9%) 1/27 (3.7%) 6/81 (7.4%) 12/95 (12.6%) 0/24 (0%)
    Thrombocytopenia 0/58 (0%) 0/27 (0%) 4/81 (4.9%) 2/95 (2.1%) 0/24 (0%)
    Anaemia 2/58 (3.4%) 0/27 (0%) 2/81 (2.5%) 1/95 (1.1%) 0/24 (0%)
    Hyperviscosity syndrome 0/58 (0%) 0/27 (0%) 1/81 (1.2%) 0/95 (0%) 0/24 (0%)
    Leukocytosis 0/58 (0%) 0/27 (0%) 0/81 (0%) 1/95 (1.1%) 0/24 (0%)
    Leukostasis syndrome 0/58 (0%) 0/27 (0%) 0/81 (0%) 1/95 (1.1%) 0/24 (0%)
    Pancytopenia 1/58 (1.7%) 0/27 (0%) 0/81 (0%) 0/95 (0%) 0/24 (0%)
    Cardiac disorders
    Tachycardia 0/58 (0%) 0/27 (0%) 0/81 (0%) 2/95 (2.1%) 0/24 (0%)
    Atrial fibrillation 0/58 (0%) 0/27 (0%) 0/81 (0%) 1/95 (1.1%) 0/24 (0%)
    Cardiac arrest 1/58 (1.7%) 0/27 (0%) 0/81 (0%) 0/95 (0%) 0/24 (0%)
    Cardiac failure 0/58 (0%) 0/27 (0%) 1/81 (1.2%) 0/95 (0%) 0/24 (0%)
    Left ventricular dysfunction 1/58 (1.7%) 0/27 (0%) 0/81 (0%) 0/95 (0%) 0/24 (0%)
    Palpitations 1/58 (1.7%) 0/27 (0%) 0/81 (0%) 0/95 (0%) 0/24 (0%)
    Eye disorders
    Cataract 0/58 (0%) 1/27 (3.7%) 0/81 (0%) 1/95 (1.1%) 0/24 (0%)
    Eye haemorrhage 0/58 (0%) 0/27 (0%) 1/81 (1.2%) 0/95 (0%) 0/24 (0%)
    Retinal detachment 0/58 (0%) 0/27 (0%) 1/81 (1.2%) 0/95 (0%) 0/24 (0%)
    Vision blurred 0/58 (0%) 0/27 (0%) 1/81 (1.2%) 0/95 (0%) 0/24 (0%)
    Vitreous detachment 0/58 (0%) 0/27 (0%) 1/81 (1.2%) 0/95 (0%) 0/24 (0%)
    Gastrointestinal disorders
    Vomiting 2/58 (3.4%) 0/27 (0%) 1/81 (1.2%) 3/95 (3.2%) 1/24 (4.2%)
    Abdominal pain 0/58 (0%) 0/27 (0%) 1/81 (1.2%) 1/95 (1.1%) 0/24 (0%)
    Ascites 1/58 (1.7%) 0/27 (0%) 0/81 (0%) 1/95 (1.1%) 0/24 (0%)
    Diarrhoea 1/58 (1.7%) 0/27 (0%) 0/81 (0%) 1/95 (1.1%) 0/24 (0%)
    Gastric haemorrhage 0/58 (0%) 0/27 (0%) 2/81 (2.5%) 0/95 (0%) 0/24 (0%)
    Nausea 0/58 (0%) 0/27 (0%) 1/81 (1.2%) 1/95 (1.1%) 0/24 (0%)
    Constipation 0/58 (0%) 0/27 (0%) 0/81 (0%) 1/95 (1.1%) 0/24 (0%)
    Dysphagia 0/58 (0%) 0/27 (0%) 0/81 (0%) 1/95 (1.1%) 0/24 (0%)
    Gastrointestinal haemorrhage 0/58 (0%) 0/27 (0%) 0/81 (0%) 1/95 (1.1%) 0/24 (0%)
    Haematochezia 0/58 (0%) 0/27 (0%) 0/81 (0%) 1/95 (1.1%) 0/24 (0%)
    Haemorrhoidal haemorrhage 0/58 (0%) 0/27 (0%) 1/81 (1.2%) 0/95 (0%) 0/24 (0%)
    Lower gastrointestinal haemorrhage 1/58 (1.7%) 0/27 (0%) 0/81 (0%) 0/95 (0%) 0/24 (0%)
    Mouth haemorrhage 0/58 (0%) 0/27 (0%) 1/81 (1.2%) 0/95 (0%) 0/24 (0%)
    Obstruction gastric 1/58 (1.7%) 0/27 (0%) 0/81 (0%) 0/95 (0%) 0/24 (0%)
    Pancreatitis 0/58 (0%) 0/27 (0%) 0/81 (0%) 1/95 (1.1%) 0/24 (0%)
    Small intestinal obstruction 1/58 (1.7%) 0/27 (0%) 0/81 (0%) 0/95 (0%) 0/24 (0%)
    Stomatitis 0/58 (0%) 0/27 (0%) 0/81 (0%) 1/95 (1.1%) 0/24 (0%)
    Upper gastrointestinal haemorrhage 0/58 (0%) 0/27 (0%) 0/81 (0%) 1/95 (1.1%) 0/24 (0%)
    General disorders
    Pyrexia 3/58 (5.2%) 0/27 (0%) 5/81 (6.2%) 1/95 (1.1%) 0/24 (0%)
    Fatigue 0/58 (0%) 0/27 (0%) 1/81 (1.2%) 6/95 (6.3%) 0/24 (0%)
    Death 1/58 (1.7%) 0/27 (0%) 0/81 (0%) 3/95 (3.2%) 1/24 (4.2%)
    Asthenia 1/58 (1.7%) 0/27 (0%) 2/81 (2.5%) 0/95 (0%) 0/24 (0%)
    Disease progression 0/58 (0%) 0/27 (0%) 0/81 (0%) 2/95 (2.1%) 0/24 (0%)
    Multiple organ dysfunction syndrome 0/58 (0%) 0/27 (0%) 0/81 (0%) 2/95 (2.1%) 0/24 (0%)
    Gait disturbance 0/58 (0%) 0/27 (0%) 0/81 (0%) 0/95 (0%) 1/24 (4.2%)
    Non-cardiac chest pain 0/58 (0%) 0/27 (0%) 1/81 (1.2%) 0/95 (0%) 0/24 (0%)
    Pain 0/58 (0%) 0/27 (0%) 0/81 (0%) 1/95 (1.1%) 0/24 (0%)
    Performance status decreased 0/58 (0%) 0/27 (0%) 0/81 (0%) 1/95 (1.1%) 0/24 (0%)
    Sudden death 0/58 (0%) 0/27 (0%) 0/81 (0%) 1/95 (1.1%) 0/24 (0%)
    Unevaluable event 1/58 (1.7%) 0/27 (0%) 0/81 (0%) 0/95 (0%) 0/24 (0%)
    Confusional state 3/58 (5.2%) 0/27 (0%) 1/81 (1.2%) 0/95 (0%) 0/24 (0%)
    Hepatobiliary disorders
    Bile duct obstruction 0/58 (0%) 0/27 (0%) 1/81 (1.2%) 0/95 (0%) 0/24 (0%)
    Cholecystitis acute 0/58 (0%) 0/27 (0%) 0/81 (0%) 1/95 (1.1%) 0/24 (0%)
    Hyperbilirubinaemia 0/58 (0%) 0/27 (0%) 1/81 (1.2%) 0/95 (0%) 0/24 (0%)
    Infections and infestations
    Pneumonia 2/58 (3.4%) 0/27 (0%) 8/81 (9.9%) 10/95 (10.5%) 2/24 (8.3%)
    Sepsis 3/58 (5.2%) 1/27 (3.7%) 2/81 (2.5%) 14/95 (14.7%) 0/24 (0%)
    Lung infection 2/58 (3.4%) 1/27 (3.7%) 1/81 (1.2%) 4/95 (4.2%) 2/24 (8.3%)
    Bacteraemia 0/58 (0%) 0/27 (0%) 1/81 (1.2%) 4/95 (4.2%) 1/24 (4.2%)
    Staphylococcal infection 0/58 (0%) 1/27 (3.7%) 0/81 (0%) 3/95 (3.2%) 0/24 (0%)
    Upper respiratory tract infection 0/58 (0%) 0/27 (0%) 2/81 (2.5%) 2/95 (2.1%) 0/24 (0%)
    Appendicitis 0/58 (0%) 0/27 (0%) 0/81 (0%) 1/95 (1.1%) 0/24 (0%)
    Cellulitis 0/58 (0%) 0/27 (0%) 0/81 (0%) 1/95 (1.1%) 0/24 (0%)
    Device related infection 1/58 (1.7%) 0/27 (0%) 0/81 (0%) 0/95 (0%) 0/24 (0%)
    Epiglottitis 0/58 (0%) 0/27 (0%) 0/81 (0%) 1/95 (1.1%) 0/24 (0%)
    Escherichia bacteraemia 0/58 (0%) 0/27 (0%) 1/81 (1.2%) 0/95 (0%) 0/24 (0%)
    Escherichia sepsis 0/58 (0%) 0/27 (0%) 1/81 (1.2%) 0/95 (0%) 0/24 (0%)
    Gastroenteritis 0/58 (0%) 0/27 (0%) 0/81 (0%) 1/95 (1.1%) 0/24 (0%)
    Infection 0/58 (0%) 1/27 (3.7%) 0/81 (0%) 0/95 (0%) 0/24 (0%)
    Localised infection 0/58 (0%) 0/27 (0%) 0/81 (0%) 1/95 (1.1%) 0/24 (0%)
    Lower respiratory tract infection 0/58 (0%) 0/27 (0%) 1/81 (1.2%) 0/95 (0%) 0/24 (0%)
    Lung infection pseudomonal 1/58 (1.7%) 0/27 (0%) 0/81 (0%) 0/95 (0%) 0/24 (0%)
    Mastoiditis 0/58 (0%) 0/27 (0%) 0/81 (0%) 1/95 (1.1%) 0/24 (0%)
    Mucormycosis 0/58 (0%) 0/27 (0%) 0/81 (0%) 1/95 (1.1%) 0/24 (0%)
    Pharyngitis 0/58 (0%) 0/27 (0%) 0/81 (0%) 1/95 (1.1%) 0/24 (0%)
    Pneumonia fungal 0/58 (0%) 0/27 (0%) 0/81 (0%) 1/95 (1.1%) 0/24 (0%)
    Pseudomonal bacteraemia 0/58 (0%) 0/27 (0%) 0/81 (0%) 1/95 (1.1%) 0/24 (0%)
    Respiratory syncytial virus infection 0/58 (0%) 0/27 (0%) 0/81 (0%) 1/95 (1.1%) 0/24 (0%)
    Sinusitis 0/58 (0%) 0/27 (0%) 0/81 (0%) 1/95 (1.1%) 0/24 (0%)
    Skin infection 0/58 (0%) 0/27 (0%) 0/81 (0%) 1/95 (1.1%) 0/24 (0%)
    Urinary tract infection 0/58 (0%) 0/27 (0%) 1/81 (1.2%) 0/95 (0%) 0/24 (0%)
    Urosepsis 0/58 (0%) 0/27 (0%) 0/81 (0%) 0/95 (0%) 1/24 (4.2%)
    Viral upper respiratory tract infection 0/58 (0%) 0/27 (0%) 1/81 (1.2%) 0/95 (0%) 0/24 (0%)
    Injury, poisoning and procedural complications
    Fall 1/58 (1.7%) 0/27 (0%) 1/81 (1.2%) 2/95 (2.1%) 0/24 (0%)
    Contusion 0/58 (0%) 0/27 (0%) 0/81 (0%) 1/95 (1.1%) 0/24 (0%)
    Overdose 0/58 (0%) 0/27 (0%) 0/81 (0%) 0/95 (0%) 1/24 (4.2%)
    Post procedural haemorrhage 0/58 (0%) 0/27 (0%) 0/81 (0%) 1/95 (1.1%) 0/24 (0%)
    Rib fracture 0/58 (0%) 0/27 (0%) 1/81 (1.2%) 0/95 (0%) 0/24 (0%)
    Spinal fracture 0/58 (0%) 0/27 (0%) 0/81 (0%) 1/95 (1.1%) 0/24 (0%)
    Transfusion reaction 0/58 (0%) 0/27 (0%) 0/81 (0%) 1/95 (1.1%) 0/24 (0%)
    Wrist fracture 0/58 (0%) 0/27 (0%) 0/81 (0%) 1/95 (1.1%) 0/24 (0%)
    Blood alkaline phosphatase increased 0/58 (0%) 0/27 (0%) 1/81 (1.2%) 0/95 (0%) 0/24 (0%)
    Investigations
    Aspartate aminotransferase increased 0/58 (0%) 0/27 (0%) 2/81 (2.5%) 1/95 (1.1%) 0/24 (0%)
    Ejection fraction decreased 0/58 (0%) 0/27 (0%) 0/81 (0%) 1/95 (1.1%) 1/24 (4.2%)
    Alanine aminotransferase increased 0/58 (0%) 0/27 (0%) 1/81 (1.2%) 0/95 (0%) 0/24 (0%)
    Metabolism and nutrition disorders
    Dehydration 2/58 (3.4%) 0/27 (0%) 3/81 (3.7%) 5/95 (5.3%) 0/24 (0%)
    Hyponatraemia 0/58 (0%) 1/27 (3.7%) 2/81 (2.5%) 0/95 (0%) 1/24 (4.2%)
    Fluid overload 0/58 (0%) 0/27 (0%) 2/81 (2.5%) 0/95 (0%) 0/24 (0%)
    Hypercalcaemia 0/58 (0%) 0/27 (0%) 1/81 (1.2%) 0/95 (0%) 1/24 (4.2%)
    Hypoglycaemia 1/58 (1.7%) 1/27 (3.7%) 0/81 (0%) 0/95 (0%) 0/24 (0%)
    Decreased appetite 0/58 (0%) 0/27 (0%) 0/81 (0%) 1/95 (1.1%) 0/24 (0%)
    Hyperamylasaemia 1/58 (1.7%) 0/27 (0%) 0/81 (0%) 0/95 (0%) 0/24 (0%)
    Hypercreatininaemia 0/58 (0%) 0/27 (0%) 0/81 (0%) 1/95 (1.1%) 0/24 (0%)
    Hyperglycaemia 0/58 (0%) 1/27 (3.7%) 0/81 (0%) 0/95 (0%) 0/24 (0%)
    Hyperkalaemia 0/58 (0%) 0/27 (0%) 0/81 (0%) 1/95 (1.1%) 0/24 (0%)
    Hypophosphataemia 0/58 (0%) 0/27 (0%) 0/81 (0%) 1/95 (1.1%) 0/24 (0%)
    Headache 0/58 (0%) 0/27 (0%) 0/81 (0%) 1/95 (1.1%) 0/24 (0%)
    Musculoskeletal and connective tissue disorders
    Muscular weakness 1/58 (1.7%) 0/27 (0%) 0/81 (0%) 2/95 (2.1%) 0/24 (0%)
    Flank pain 0/58 (0%) 0/27 (0%) 0/81 (0%) 1/95 (1.1%) 0/24 (0%)
    Joint effusion 0/58 (0%) 0/27 (0%) 0/81 (0%) 1/95 (1.1%) 0/24 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Malignant neoplasm progression 0/58 (0%) 0/27 (0%) 1/81 (1.2%) 4/95 (4.2%) 0/24 (0%)
    Tumour pain 0/58 (0%) 1/27 (3.7%) 0/81 (0%) 0/95 (0%) 0/24 (0%)
    Nervous system disorders
    Central nervous system haemorrhage 0/58 (0%) 0/27 (0%) 0/81 (0%) 2/95 (2.1%) 0/24 (0%)
    Cerebral haemorrhage 0/58 (0%) 0/27 (0%) 1/81 (1.2%) 1/95 (1.1%) 0/24 (0%)
    Encephalopathy 0/58 (0%) 0/27 (0%) 1/81 (1.2%) 1/95 (1.1%) 0/24 (0%)
    Seizure 1/58 (1.7%) 0/27 (0%) 0/81 (0%) 1/95 (1.1%) 0/24 (0%)
    Dysarthria 0/58 (0%) 0/27 (0%) 1/81 (1.2%) 0/95 (0%) 0/24 (0%)
    Encephalitis toxic 1/58 (1.7%) 0/27 (0%) 0/81 (0%) 0/95 (0%) 0/24 (0%)
    Facial paralysis 0/58 (0%) 0/27 (0%) 1/81 (1.2%) 0/95 (0%) 0/24 (0%)
    Guillain-Barre syndrome 0/58 (0%) 0/27 (0%) 0/81 (0%) 1/95 (1.1%) 0/24 (0%)
    Haemorrhage intracranial 0/58 (0%) 0/27 (0%) 0/81 (0%) 1/95 (1.1%) 0/24 (0%)
    Lethargy 1/58 (1.7%) 0/27 (0%) 0/81 (0%) 0/95 (0%) 0/24 (0%)
    Nervous system disorder 0/58 (0%) 0/27 (0%) 0/81 (0%) 1/95 (1.1%) 0/24 (0%)
    Somnolence 0/58 (0%) 0/27 (0%) 0/81 (0%) 1/95 (1.1%) 0/24 (0%)
    Spinal cord compression 1/58 (1.7%) 0/27 (0%) 0/81 (0%) 0/95 (0%) 0/24 (0%)
    Syncope 0/58 (0%) 0/27 (0%) 0/81 (0%) 1/95 (1.1%) 0/24 (0%)
    Transient ischaemic attack 0/58 (0%) 0/27 (0%) 0/81 (0%) 0/95 (0%) 1/24 (4.2%)
    Psychiatric disorders
    Delirium 0/58 (0%) 0/27 (0%) 2/81 (2.5%) 0/95 (0%) 0/24 (0%)
    Suicide attempt 1/58 (1.7%) 1/27 (3.7%) 0/81 (0%) 0/95 (0%) 0/24 (0%)
    Psychotic disorder 0/58 (0%) 0/27 (0%) 1/81 (1.2%) 0/95 (0%) 0/24 (0%)
    Renal and urinary disorders
    Acute kidney injury 1/58 (1.7%) 0/27 (0%) 4/81 (4.9%) 1/95 (1.1%) 0/24 (0%)
    Renal impairment 0/58 (0%) 0/27 (0%) 2/81 (2.5%) 0/95 (0%) 0/24 (0%)
    Urinary tract obstruction 1/58 (1.7%) 0/27 (0%) 0/81 (0%) 0/95 (0%) 0/24 (0%)
    Respiratory, thoracic and mediastinal disorders
    Hypoxia 0/58 (0%) 0/27 (0%) 2/81 (2.5%) 2/95 (2.1%) 0/24 (0%)
    Dyspnoea 1/58 (1.7%) 0/27 (0%) 0/81 (0%) 1/95 (1.1%) 1/24 (4.2%)
    Epistaxis 0/58 (0%) 0/27 (0%) 1/81 (1.2%) 2/95 (2.1%) 0/24 (0%)
    Respiratory failure 0/58 (0%) 0/27 (0%) 0/81 (0%) 3/95 (3.2%) 0/24 (0%)
    Haemoptysis 0/58 (0%) 0/27 (0%) 0/81 (0%) 2/95 (2.1%) 0/24 (0%)
    Pleural effusion 1/58 (1.7%) 0/27 (0%) 0/81 (0%) 1/95 (1.1%) 0/24 (0%)
    Pneumonia aspiration 1/58 (1.7%) 0/27 (0%) 1/81 (1.2%) 0/95 (0%) 0/24 (0%)
    Pulmonary embolism 1/58 (1.7%) 1/27 (3.7%) 0/81 (0%) 0/95 (0%) 0/24 (0%)
    Pulmonary oedema 0/58 (0%) 0/27 (0%) 1/81 (1.2%) 0/95 (0%) 0/24 (0%)
    Acute respiratory distress syndrome 0/58 (0%) 0/27 (0%) 0/81 (0%) 1/95 (1.1%) 0/24 (0%)
    Lung consolidation 0/58 (0%) 0/27 (0%) 0/81 (0%) 0/95 (0%) 1/24 (4.2%)
    Pneumothorax 1/58 (1.7%) 0/27 (0%) 0/81 (0%) 0/95 (0%) 0/24 (0%)
    Respiratory arrest 0/58 (0%) 0/27 (0%) 0/81 (0%) 1/95 (1.1%) 1/24 (4.2%)
    Skin and subcutaneous tissue disorders
    Swelling face 0/58 (0%) 0/27 (0%) 1/81 (1.2%) 0/95 (0%) 0/24 (0%)
    Surgical and medical procedures
    Small intestinal resection 1/58 (1.7%) 0/27 (0%) 0/81 (0%) 0/95 (0%) 0/24 (0%)
    Vascular disorders
    Embolism 2/58 (3.4%) 0/27 (0%) 0/81 (0%) 2/95 (2.1%) 0/24 (0%)
    Hypotension 1/58 (1.7%) 0/27 (0%) 2/81 (2.5%) 1/95 (1.1%) 0/24 (0%)
    Other (Not Including Serious) Adverse Events
    Diffuse Large B-cell Lymphoma (DLBCL) Non-Hodgkin Lymphoma (NHL) Excluding DLBCL Multiple Myeloma (MM) Acute Myeloid Leukemia (AML) Other Hematological Malignancies (ALL, CML and CLL)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 58/58 (100%) 27/27 (100%) 80/81 (98.8%) 94/95 (98.9%) 24/24 (100%)
    Blood and lymphatic system disorders
    Thrombocytopenia 39/58 (67.2%) 15/27 (55.6%) 52/81 (64.2%) 47/95 (49.5%) 17/24 (70.8%)
    Anaemia 34/58 (58.6%) 14/27 (51.9%) 42/81 (51.9%) 46/95 (48.4%) 16/24 (66.7%)
    Neutropenia 23/58 (39.7%) 12/27 (44.4%) 31/81 (38.3%) 23/95 (24.2%) 10/24 (41.7%)
    Leukopenia 11/58 (19%) 5/27 (18.5%) 11/81 (13.6%) 15/95 (15.8%) 8/24 (33.3%)
    Lymphopenia 6/58 (10.3%) 2/27 (7.4%) 7/81 (8.6%) 7/95 (7.4%) 6/24 (25%)
    Febrile neutropenia 1/58 (1.7%) 1/27 (3.7%) 3/81 (3.7%) 13/95 (13.7%) 1/24 (4.2%)
    Leukocytosis 0/58 (0%) 0/27 (0%) 0/81 (0%) 9/95 (9.5%) 3/24 (12.5%)
    Cardiac disorders
    Tachycardia 1/58 (1.7%) 1/27 (3.7%) 4/81 (4.9%) 3/95 (3.2%) 2/24 (8.3%)
    Sinus tachycardia 4/58 (6.9%) 0/27 (0%) 1/81 (1.2%) 3/95 (3.2%) 0/24 (0%)
    Palpitations 2/58 (3.4%) 2/27 (7.4%) 1/81 (1.2%) 0/95 (0%) 1/24 (4.2%)
    Ear and labyrinth disorders
    Hypoacusis 3/58 (5.2%) 1/27 (3.7%) 2/81 (2.5%) 3/95 (3.2%) 0/24 (0%)
    Tinnitus 0/58 (0%) 1/27 (3.7%) 1/81 (1.2%) 5/95 (5.3%) 0/24 (0%)
    Eye disorders
    Vision blurred 15/58 (25.9%) 4/27 (14.8%) 21/81 (25.9%) 21/95 (22.1%) 6/24 (25%)
    Cataract 2/58 (3.4%) 2/27 (7.4%) 6/81 (7.4%) 3/95 (3.2%) 1/24 (4.2%)
    Visual impairment 5/58 (8.6%) 1/27 (3.7%) 3/81 (3.7%) 1/95 (1.1%) 0/24 (0%)
    Photopsia 2/58 (3.4%) 0/27 (0%) 5/81 (6.2%) 0/95 (0%) 2/24 (8.3%)
    Dry eye 2/58 (3.4%) 2/27 (7.4%) 1/81 (1.2%) 2/95 (2.1%) 0/24 (0%)
    Eye pain 0/58 (0%) 3/27 (11.1%) 0/81 (0%) 0/95 (0%) 0/24 (0%)
    Gastrointestinal disorders
    Nausea 38/58 (65.5%) 18/27 (66.7%) 64/81 (79%) 55/95 (57.9%) 18/24 (75%)
    Vomiting 25/58 (43.1%) 11/27 (40.7%) 40/81 (49.4%) 39/95 (41.1%) 9/24 (37.5%)
    Diarrhoea 24/58 (41.4%) 9/27 (33.3%) 32/81 (39.5%) 46/95 (48.4%) 10/24 (41.7%)
    Constipation 15/58 (25.9%) 9/27 (33.3%) 15/81 (18.5%) 29/95 (30.5%) 6/24 (25%)
    Abdominal pain 11/58 (19%) 3/27 (11.1%) 9/81 (11.1%) 10/95 (10.5%) 4/24 (16.7%)
    Dyspepsia 8/58 (13.8%) 2/27 (7.4%) 9/81 (11.1%) 5/95 (5.3%) 1/24 (4.2%)
    Stomatitis 4/58 (6.9%) 1/27 (3.7%) 1/81 (1.2%) 17/95 (17.9%) 2/24 (8.3%)
    Dysphagia 3/58 (5.2%) 1/27 (3.7%) 5/81 (6.2%) 5/95 (5.3%) 0/24 (0%)
    Dry mouth 2/58 (3.4%) 2/27 (7.4%) 3/81 (3.7%) 6/95 (6.3%) 0/24 (0%)
    Gingival bleeding 1/58 (1.7%) 1/27 (3.7%) 3/81 (3.7%) 5/95 (5.3%) 0/24 (0%)
    Haemorrhoids 0/58 (0%) 0/27 (0%) 2/81 (2.5%) 6/95 (6.3%) 0/24 (0%)
    General disorders
    Fatigue 39/58 (67.2%) 13/27 (48.1%) 62/81 (76.5%) 67/95 (70.5%) 16/24 (66.7%)
    Pyrexia 21/58 (36.2%) 4/27 (14.8%) 22/81 (27.2%) 20/95 (21.1%) 1/24 (4.2%)
    Oedema peripheral 13/58 (22.4%) 2/27 (7.4%) 8/81 (9.9%) 21/95 (22.1%) 2/24 (8.3%)
    Asthenia 2/58 (3.4%) 4/27 (14.8%) 14/81 (17.3%) 7/95 (7.4%) 0/24 (0%)
    Chills 4/58 (6.9%) 5/27 (18.5%) 7/81 (8.6%) 7/95 (7.4%) 2/24 (8.3%)
    Gait disturbance 6/58 (10.3%) 1/27 (3.7%) 7/81 (8.6%) 2/95 (2.1%) 2/24 (8.3%)
    Malaise 5/58 (8.6%) 2/27 (7.4%) 5/81 (6.2%) 2/95 (2.1%) 1/24 (4.2%)
    Non-cardiac chest pain 2/58 (3.4%) 1/27 (3.7%) 8/81 (9.9%) 4/95 (4.2%) 0/24 (0%)
    Oedema 2/58 (3.4%) 0/27 (0%) 1/81 (1.2%) 5/95 (5.3%) 1/24 (4.2%)
    Peripheral swelling 4/58 (6.9%) 0/27 (0%) 1/81 (1.2%) 0/95 (0%) 0/24 (0%)
    Hepatobiliary disorders
    Hyperbilirubinaemia 0/58 (0%) 0/27 (0%) 4/81 (4.9%) 4/95 (4.2%) 2/24 (8.3%)
    Infections and infestations
    Urinary tract infection 5/58 (8.6%) 3/27 (11.1%) 7/81 (8.6%) 5/95 (5.3%) 4/24 (16.7%)
    Upper respiratory tract infection 2/58 (3.4%) 2/27 (7.4%) 9/81 (11.1%) 4/95 (4.2%) 1/24 (4.2%)
    Lung infection 5/58 (8.6%) 2/27 (7.4%) 3/81 (3.7%) 3/95 (3.2%) 1/24 (4.2%)
    Pneumonia 0/58 (0%) 0/27 (0%) 4/81 (4.9%) 9/95 (9.5%) 1/24 (4.2%)
    Oral infection 0/58 (0%) 2/27 (7.4%) 0/81 (0%) 0/95 (0%) 0/24 (0%)
    Injury, poisoning and procedural complications
    Fall 4/58 (6.9%) 2/27 (7.4%) 8/81 (9.9%) 8/95 (8.4%) 4/24 (16.7%)
    Contusion 3/58 (5.2%) 0/27 (0%) 6/81 (7.4%) 5/95 (5.3%) 4/24 (16.7%)
    Investigations
    Weight decreased 14/58 (24.1%) 10/27 (37%) 32/81 (39.5%) 31/95 (32.6%) 3/24 (12.5%)
    Alanine aminotransferase increased 7/58 (12.1%) 2/27 (7.4%) 8/81 (9.9%) 10/95 (10.5%) 2/24 (8.3%)
    Aspartate aminotransferase increased 5/58 (8.6%) 1/27 (3.7%) 7/81 (8.6%) 10/95 (10.5%) 2/24 (8.3%)
    Electrocardiogram QT prolonged 2/58 (3.4%) 1/27 (3.7%) 3/81 (3.7%) 10/95 (10.5%) 5/24 (20.8%)
    International normalised ratio increased 0/58 (0%) 0/27 (0%) 3/81 (3.7%) 7/95 (7.4%) 0/24 (0%)
    Metabolism and nutrition disorders
    Decreased appetite 34/58 (58.6%) 16/27 (59.3%) 54/81 (66.7%) 62/95 (65.3%) 13/24 (54.2%)
    Hyponatraemia 25/58 (43.1%) 7/27 (25.9%) 36/81 (44.4%) 34/95 (35.8%) 11/24 (45.8%)
    Hypokalaemia 14/58 (24.1%) 5/27 (18.5%) 12/81 (14.8%) 22/95 (23.2%) 2/24 (8.3%)
    Dehydration 7/58 (12.1%) 4/27 (14.8%) 27/81 (33.3%) 15/95 (15.8%) 1/24 (4.2%)
    Hypercreatininaemia 10/58 (17.2%) 0/27 (0%) 23/81 (28.4%) 18/95 (18.9%) 3/24 (12.5%)
    Hypomagnesaemia 14/58 (24.1%) 4/27 (14.8%) 6/81 (7.4%) 19/95 (20%) 1/24 (4.2%)
    Hyperglycaemia 8/58 (13.8%) 7/27 (25.9%) 6/81 (7.4%) 18/95 (18.9%) 3/24 (12.5%)
    Hypocalcaemia 4/58 (6.9%) 6/27 (22.2%) 7/81 (8.6%) 18/95 (18.9%) 3/24 (12.5%)
    Hypophosphataemia 6/58 (10.3%) 4/27 (14.8%) 6/81 (7.4%) 13/95 (13.7%) 1/24 (4.2%)
    Hyperkalaemia 4/58 (6.9%) 3/27 (11.1%) 3/81 (3.7%) 11/95 (11.6%) 1/24 (4.2%)
    Hyperuricaemia 2/58 (3.4%) 4/27 (14.8%) 5/81 (6.2%) 9/95 (9.5%) 1/24 (4.2%)
    Hypoalbuminaemia 5/58 (8.6%) 1/27 (3.7%) 1/81 (1.2%) 10/95 (10.5%) 1/24 (4.2%)
    Hyperamylasaemia 5/58 (8.6%) 0/27 (0%) 3/81 (3.7%) 6/95 (6.3%) 0/24 (0%)
    Hyperlipasaemia 2/58 (3.4%) 0/27 (0%) 6/81 (7.4%) 5/95 (5.3%) 0/24 (0%)
    Hypermagnesaemia 3/58 (5.2%) 2/27 (7.4%) 1/81 (1.2%) 2/95 (2.1%) 0/24 (0%)
    Hypercalcaemia 0/58 (0%) 1/27 (3.7%) 3/81 (3.7%) 1/95 (1.1%) 2/24 (8.3%)
    Musculoskeletal and connective tissue disorders
    Back pain 12/58 (20.7%) 2/27 (7.4%) 19/81 (23.5%) 13/95 (13.7%) 1/24 (4.2%)
    Muscular weakness 9/58 (15.5%) 4/27 (14.8%) 13/81 (16%) 15/95 (15.8%) 3/24 (12.5%)
    Arthralgia 3/58 (5.2%) 1/27 (3.7%) 7/81 (8.6%) 14/95 (14.7%) 4/24 (16.7%)
    Pain in extremity 4/58 (6.9%) 2/27 (7.4%) 6/81 (7.4%) 6/95 (6.3%) 1/24 (4.2%)
    Myalgia 4/58 (6.9%) 2/27 (7.4%) 5/81 (6.2%) 6/95 (6.3%) 1/24 (4.2%)
    Muscle spasms 4/58 (6.9%) 1/27 (3.7%) 6/81 (7.4%) 4/95 (4.2%) 0/24 (0%)
    Musculoskeletal chest pain 4/58 (6.9%) 2/27 (7.4%) 5/81 (6.2%) 0/95 (0%) 1/24 (4.2%)
    Neck pain 3/58 (5.2%) 2/27 (7.4%) 2/81 (2.5%) 2/95 (2.1%) 0/24 (0%)
    Bone pain 0/58 (0%) 0/27 (0%) 1/81 (1.2%) 5/95 (5.3%) 0/24 (0%)
    Nervous system disorders
    Dysgeusia 13/58 (22.4%) 6/27 (22.2%) 16/81 (19.8%) 22/95 (23.2%) 1/24 (4.2%)
    Dizziness 14/58 (24.1%) 5/27 (18.5%) 13/81 (16%) 20/95 (21.1%) 5/24 (20.8%)
    Headache 7/58 (12.1%) 4/27 (14.8%) 11/81 (13.6%) 16/95 (16.8%) 5/24 (20.8%)
    Peripheral sensory neuropathy 2/58 (3.4%) 2/27 (7.4%) 4/81 (4.9%) 2/95 (2.1%) 4/24 (16.7%)
    Neuropathy peripheral 6/58 (10.3%) 2/27 (7.4%) 2/81 (2.5%) 3/95 (3.2%) 0/24 (0%)
    Syncope 2/58 (3.4%) 2/27 (7.4%) 5/81 (6.2%) 3/95 (3.2%) 0/24 (0%)
    Amnesia 1/58 (1.7%) 2/27 (7.4%) 1/81 (1.2%) 3/95 (3.2%) 0/24 (0%)
    Balance disorder 3/58 (5.2%) 2/27 (7.4%) 2/81 (2.5%) 0/95 (0%) 0/24 (0%)
    Dysarthria 3/58 (5.2%) 1/27 (3.7%) 0/81 (0%) 1/95 (1.1%) 0/24 (0%)
    Psychiatric disorders
    Confusional state 8/58 (13.8%) 8/27 (29.6%) 15/81 (18.5%) 15/95 (15.8%) 2/24 (8.3%)
    Insomnia 8/58 (13.8%) 4/27 (14.8%) 8/81 (9.9%) 9/95 (9.5%) 2/24 (8.3%)
    Anxiety 7/58 (12.1%) 0/27 (0%) 4/81 (4.9%) 7/95 (7.4%) 0/24 (0%)
    Depression 3/58 (5.2%) 2/27 (7.4%) 6/81 (7.4%) 4/95 (4.2%) 1/24 (4.2%)
    Agitation 5/58 (8.6%) 0/27 (0%) 6/81 (7.4%) 2/95 (2.1%) 2/24 (8.3%)
    Renal and urinary disorders
    Haematuria 3/58 (5.2%) 1/27 (3.7%) 5/81 (6.2%) 6/95 (6.3%) 3/24 (12.5%)
    Proteinuria 3/58 (5.2%) 2/27 (7.4%) 4/81 (4.9%) 3/95 (3.2%) 4/24 (16.7%)
    Urinary incontinence 1/58 (1.7%) 3/27 (11.1%) 2/81 (2.5%) 2/95 (2.1%) 2/24 (8.3%)
    Pollakiuria 2/58 (3.4%) 0/27 (0%) 2/81 (2.5%) 5/95 (5.3%) 0/24 (0%)
    Dysuria 0/58 (0%) 0/27 (0%) 1/81 (1.2%) 4/95 (4.2%) 2/24 (8.3%)
    Urinary retention 3/58 (5.2%) 0/27 (0%) 0/81 (0%) 0/95 (0%) 0/24 (0%)
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea 15/58 (25.9%) 8/27 (29.6%) 20/81 (24.7%) 32/95 (33.7%) 6/24 (25%)
    Cough 15/58 (25.9%) 6/27 (22.2%) 18/81 (22.2%) 15/95 (15.8%) 3/24 (12.5%)
    Epistaxis 6/58 (10.3%) 1/27 (3.7%) 16/81 (19.8%) 23/95 (24.2%) 3/24 (12.5%)
    Productive cough 6/58 (10.3%) 5/27 (18.5%) 1/81 (1.2%) 6/95 (6.3%) 0/24 (0%)
    Oropharyngeal pain 1/58 (1.7%) 3/27 (11.1%) 2/81 (2.5%) 6/95 (6.3%) 0/24 (0%)
    Nasal congestion 4/58 (6.9%) 0/27 (0%) 3/81 (3.7%) 2/95 (2.1%) 1/24 (4.2%)
    Pleural effusion 3/58 (5.2%) 1/27 (3.7%) 3/81 (3.7%) 1/95 (1.1%) 1/24 (4.2%)
    Rhinorrhoea 1/58 (1.7%) 1/27 (3.7%) 1/81 (1.2%) 5/95 (5.3%) 0/24 (0%)
    Skin and subcutaneous tissue disorders
    Night sweats 6/58 (10.3%) 2/27 (7.4%) 6/81 (7.4%) 5/95 (5.3%) 3/24 (12.5%)
    Alopecia 2/58 (3.4%) 3/27 (11.1%) 7/81 (8.6%) 2/95 (2.1%) 2/24 (8.3%)
    Petechiae 0/58 (0%) 1/27 (3.7%) 5/81 (6.2%) 8/95 (8.4%) 2/24 (8.3%)
    Hyperhidrosis 2/58 (3.4%) 2/27 (7.4%) 5/81 (6.2%) 6/95 (6.3%) 0/24 (0%)
    Skin lesion 0/58 (0%) 2/27 (7.4%) 1/81 (1.2%) 3/95 (3.2%) 0/24 (0%)
    Vascular disorders
    Hypotension 7/58 (12.1%) 5/27 (18.5%) 9/81 (11.1%) 19/95 (20%) 2/24 (8.3%)
    Hypertension 5/58 (8.6%) 2/27 (7.4%) 1/81 (1.2%) 9/95 (9.5%) 3/24 (12.5%)
    Orthostatic hypotension 1/58 (1.7%) 1/27 (3.7%) 0/81 (0%) 5/95 (5.3%) 0/24 (0%)
    Hot flush 1/58 (1.7%) 2/27 (7.4%) 0/81 (0%) 0/95 (0%) 0/24 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Jatin Shah, MD
    Organization Karyopharm Therapeutics Inc.
    Phone (617) 658-0600
    Email jshah@karyopharm.com
    Responsible Party:
    Karyopharm Therapeutics Inc
    ClinicalTrials.gov Identifier:
    NCT01607892
    Other Study ID Numbers:
    • KCP-330-001
    First Posted:
    May 30, 2012
    Last Update Posted:
    Apr 1, 2021
    Last Verified:
    Mar 1, 2021