Hematological Malignancies
Conditions
Keywords
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
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.
Interventions
DRUGKPT-330
Sponsors
Karyopharm Therapeutics Inc
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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). |
| 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 \[kg\]). |
| 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). |
| 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. |
| 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). |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
Canada, Denmark, United States
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 details
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).
Participants by arm
| Arm | Count |
|---|---|
| Diffuse Large B-cell Lymphoma (DLBCL) Participants with DLBCL received Selinexor in different Schedules; Schedule 1: \<= 12 milligram per square meter (mg/m\^2) per orally (PO) alternating 3 times per week with twice weekly dosing (1 day between doses); Schedule 2: \> 12 mg/m\^2 PO 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 8: \>=40 mg/m\^2 PO twice weekly (1 day between doses) during Weeks 1 and 2; Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab intravenous (IV) once weekly for Weeks 1-4 during different cycles. Each cycle was of 28 days (Schedule 8: 21 days of cycle) or 10 scheduled selinexor doses. | 58 |
| Non-Hodgkin Lymphoma (NHL) Excluding DLBCL Participants with NHL received Selinexor in different Schedules; Schedule 1: \<= 12 mg/m\^2 PO alternating 3 times per week with twice weekly dosing (1 day between doses); Schedule 2: \> 12 mg/m\^2 PO 3 times weekly for week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs 1 day apart (Schedule 3); Schedule 7: \>=45 mg/m\^2 PO once weekly (6 days between doses) to evaluate vs twice weekly (Schedules 3, 4, 5, and 6); Schedule 8: \>=40 mg/m\^2 PO twice weekly \[1 Day between doses\] during weeks 1 and 2; Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab IV once weekly for Weeks 1-4) during different cycles. Each cycle was of 28 days (Schedule 8: 21 days of cycle) or 10 scheduled selinexor doses. | 27 |
| Multiple Myeloma (MM) Participants with MM received Selinexor in different Schedules; Schedule 1: \<= 12 mg/m\^2 PO alternating 3 times per week with twice weekly dosing (1 Day between doses); Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; 3 doses (36 mg/m\^2 total) in the 1-week run-in period; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 6: \>= 35 mg/m\^2 PO twice weekly with dexamethasone (20 mg twice weekly) on Days of twice weekly Selinexor dosing; Schedule 11: Group A: 40 mg; Group B: 60 mg; Group C: 80 mg twice weekly (Weeks 1, 2, and 3) at 3 fixed dose levels during different cycles. Each cycle was of 28 days or 10 scheduled selinexor doses. | 81 |
| Acute Myeloid Leukemia (AML) Participants with AML received Selinexor in different Schedules; Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly (1 day between doses); Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3), Schedule 7: \>=45 mg/m\^2 PO once weekly (6 Days between doses) to evaluate vs. twice weekly (Schedules 3, 4, 5, and 6); Schedule 8: \>=40 mg/m\^2 PO twice weekly (1 Day between doses) during Weeks 1 and 2; Schedule 10: \>= 55 mg/m\^2 PO twice weekly PO (Weeks 1 and 2) in participants with AML/18-Day treatment-free interval) during different cycles. Each cycle was of 28 days (for schedule 8: 21-day of cycle) or 10 scheduled selinexor doses. | 95 |
| Other Hematological Malignancies (ALL, CML and CLL) Participants with other hematological malignancies (Acute lymphoblastic leukemia \[ALL\], Chronic myelogenous leukemia \[CML\] and chronic lymphocytic leukemia \[CLL\]) received Schedule 2: \> 12 mg/m\^2 3 times weekly for Week -1 followed by same dosing frequency as schedule 1 for Weeks 1-4; Schedule 3: \>=30 mg/m\^2 PO twice weekly \[1 day between doses\]; Schedule 4: \>=23 mg/m\^2 PO twice weekly (0 days between doses) to evaluate consecutive dosing; Schedule 5: \>=30 mg/m\^2 PO twice weekly (2 days between doses) to evaluate dosing 2 days apart vs. 1 day apart (Schedule 3); Schedule 7: \>=45 mg/m\^2 PO once weekly (6 Days between doses) to evaluate vs. twice weekly (Schedules 3, 4, 5, and 6); Schedule 9: \>=45 mg/m\^2 PO twice weekly in combination with 375 mg/m\^2 dose of rituximab IV once weekly for Weeks 1-4 during different cycles. Each cycle was of 28 days or 10 scheduled selinexor doses. | 24 |
| Total | 285 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Consent withdrawn by participant | 9 | 4 | 24 | 14 | 4 |
| Overall Study | Death | 4 | 2 | 8 | 10 | 3 |
| Overall Study | Disease progression | 38 | 13 | 37 | 57 | 9 |
| Overall Study | Incidence or severity of Adverse events | 3 | 3 | 7 | 2 | 6 |
| Overall Study | Intercurrent illness | 1 | 0 | 0 | 3 | 0 |
| Overall Study | Investigator discretion | 2 | 4 | 4 | 8 | 0 |
| Overall Study | Need of treatment not allowed per protocol | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Non-Compliance with study procedures | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Other treatments became available | 1 | 1 | 0 | 0 | 2 |
Baseline characteristics
| Characteristic | Total | Other Hematological Malignancies (ALL, CML and CLL) | Acute Myeloid Leukemia (AML) | Multiple Myeloma (MM) | Non-Hodgkin Lymphoma (NHL) Excluding DLBCL | Diffuse Large B-cell Lymphoma (DLBCL) |
|---|---|---|---|---|---|---|
| Age, Continuous | 61.9 years STANDARD_DEVIATION 13.79 | 60.9 years STANDARD_DEVIATION 15.23 | 65.6 years STANDARD_DEVIATION 15.33 | 62.1 years STANDARD_DEVIATION 8.76 | 58.0 years STANDARD_DEVIATION 15.9 | 57.8 years STANDARD_DEVIATION 14 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants | 0 Participants | 2 Participants | 4 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 258 Participants | 23 Participants | 88 Participants | 72 Participants | 23 Participants | 52 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 18 Participants | 1 Participants | 5 Participants | 5 Participants | 3 Participants | 4 Participants |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 7 Participants | 1 Participants | 1 Participants | 4 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Black | 22 Participants | 1 Participants | 5 Participants | 11 Participants | 3 Participants | 2 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 3 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Unknown/Not Reported | 5 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 4 Participants |
| Race/Ethnicity, Customized White | 248 Participants | 23 Participants | 88 Participants | 65 Participants | 20 Participants | 52 Participants |
| Sex: Female, Male Female | 123 Participants | 8 Participants | 40 Participants | 38 Participants | 9 Participants | 28 Participants |
| Sex: Female, Male Male | 162 Participants | 16 Participants | 55 Participants | 43 Participants | 18 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 58 / 58 | 27 / 27 | 80 / 81 | 94 / 95 | 24 / 24 |
| serious Total, serious adverse events | 33 / 58 | 7 / 27 | 52 / 81 | 73 / 95 | 13 / 24 |
Outcome results
Primary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
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)
Population: Safety population consisted of all participants who received at least 1 dose of selinexor.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Diffuse Large B-cell Lymphoma (DLBCL) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | At Least One TEAE | 58 Participants |
| Diffuse Large B-cell Lymphoma (DLBCL) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | At Least One Serious TEAE | 33 Participants |
| Non-Hodgkin Lymphoma (NHL) Excluding DLBCL | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | At Least One TEAE | 27 Participants |
| Non-Hodgkin Lymphoma (NHL) Excluding DLBCL | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | At Least One Serious TEAE | 7 Participants |
| Multiple Myeloma (MM) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | At Least One TEAE | 81 Participants |
| Multiple Myeloma (MM) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | At Least One Serious TEAE | 52 Participants |
| Acute Myeloid Leukemia (AML) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | At Least One Serious TEAE | 73 Participants |
| Acute Myeloid Leukemia (AML) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | At Least One TEAE | 95 Participants |
| Other Hematological Malignancies (ALL, CML and CLL) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | At Least One TEAE | 24 Participants |
| Other Hematological Malignancies (ALL, CML and CLL) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | At Least One Serious TEAE | 13 Participants |
Primary
Recommended Phase 2 Dose (RP2D) of Selinexor
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)
Population: Efficacy analysis set included all participants who had either completed 1 cycle of treatment or discontinued treatment prior to completing the first cycle due to documented progressive disease (PD), death related to disease, or treatment-related toxicity. Here, data was not planned and analyzed based on individual specific disease, hence overall data was analyzed for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Diffuse Large B-cell Lymphoma (DLBCL) | Recommended Phase 2 Dose (RP2D) of Selinexor | 35 milligram per square meter (mg/m^2) |
Secondary
Apparent Total Body Clearance, Uncorrected for Fraction Absorbed (Cl/F) of Selinexor
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Diffuse Large B-cell Lymphoma (DLBCL) | Apparent Total Body Clearance, Uncorrected for Fraction Absorbed (Cl/F) of Selinexor | 0.19 Liter per hour per kilogram (L/h/kg) | — |
| Non-Hodgkin Lymphoma (NHL) Excluding DLBCL | Apparent Total Body Clearance, Uncorrected for Fraction Absorbed (Cl/F) of Selinexor | 0.21 Liter per hour per kilogram (L/h/kg) | — |
| Multiple Myeloma (MM) | Apparent Total Body Clearance, Uncorrected for Fraction Absorbed (Cl/F) of Selinexor | 0.21 Liter per hour per kilogram (L/h/kg) | Geometric Coefficient of Variation 26.6 |
| Acute Myeloid Leukemia (AML) | Apparent Total Body Clearance, Uncorrected for Fraction Absorbed (Cl/F) of Selinexor | 0.22 Liter per hour per kilogram (L/h/kg) | Geometric Coefficient of Variation 22.8 |
| Other Hematological Malignancies (ALL, CML and CLL) | Apparent Total Body Clearance, Uncorrected for Fraction Absorbed (Cl/F) of Selinexor | 0.20 Liter per hour per kilogram (L/h/kg) | Geometric Coefficient of Variation 54.9 |
| Selinexor (30 mg/m^2) | Apparent Total Body Clearance, Uncorrected for Fraction Absorbed (Cl/F) of Selinexor | 0.21 Liter per hour per kilogram (L/h/kg) | Geometric Coefficient of Variation 25.3 |
| Selinexor (35 mg/m^2) | Apparent Total Body Clearance, Uncorrected for Fraction Absorbed (Cl/F) of Selinexor | 0.22 Liter per hour per kilogram (L/h/kg) | Geometric Coefficient of Variation 25.9 |
| Selinexor (40 mg/m^2) | Apparent Total Body Clearance, Uncorrected for Fraction Absorbed (Cl/F) of Selinexor | 0.23 Liter per hour per kilogram (L/h/kg) | Geometric Coefficient of Variation 26.2 |
| Selinexor (46 mg/m^2) | Apparent Total Body Clearance, Uncorrected for Fraction Absorbed (Cl/F) of Selinexor | 0.22 Liter per hour per kilogram (L/h/kg) | Geometric Coefficient of Variation 12.9 |
| Selinexor (55 mg/m^2) | Apparent Total Body Clearance, Uncorrected for Fraction Absorbed (Cl/F) of Selinexor | 0.20 Liter per hour per kilogram (L/h/kg) | Geometric Coefficient of Variation 24.6 |
| Selinexor (60 mg/m^2) | Apparent Total Body Clearance, Uncorrected for Fraction Absorbed (Cl/F) of Selinexor | 0.19 Liter per hour per kilogram (L/h/kg) | Geometric Coefficient of Variation 27.5 |
| Selinexor (70 mg/m^2) | Apparent Total Body Clearance, Uncorrected for Fraction Absorbed (Cl/F) of Selinexor | 0.22 Liter per hour per kilogram (L/h/kg) | Geometric Coefficient of Variation 7.8 |
| Selinexor (80 mg/m^2) | Apparent Total Body Clearance, Uncorrected for Fraction Absorbed (Cl/F) of Selinexor | NA Liter per hour per kilogram (L/h/kg) | — |
Secondary
Apparent Volume of Distribution Uncorrected for Fraction Absorbed (Vd/F) of Selinexor
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Diffuse Large B-cell Lymphoma (DLBCL) | Apparent Volume of Distribution Uncorrected for Fraction Absorbed (Vd/F) of Selinexor | 1.6 Liter per kilogram (L/kg) | — |
| Non-Hodgkin Lymphoma (NHL) Excluding DLBCL | Apparent Volume of Distribution Uncorrected for Fraction Absorbed (Vd/F) of Selinexor | 1.5 Liter per kilogram (L/kg) | — |
| Multiple Myeloma (MM) | Apparent Volume of Distribution Uncorrected for Fraction Absorbed (Vd/F) of Selinexor | 1.9 Liter per kilogram (L/kg) | Geometric Coefficient of Variation 21.2 |
| Acute Myeloid Leukemia (AML) | Apparent Volume of Distribution Uncorrected for Fraction Absorbed (Vd/F) of Selinexor | 1.9 Liter per kilogram (L/kg) | Geometric Coefficient of Variation 29.9 |
| Other Hematological Malignancies (ALL, CML and CLL) | Apparent Volume of Distribution Uncorrected for Fraction Absorbed (Vd/F) of Selinexor | 1.9 Liter per kilogram (L/kg) | Geometric Coefficient of Variation 34.1 |
| Selinexor (30 mg/m^2) | Apparent Volume of Distribution Uncorrected for Fraction Absorbed (Vd/F) of Selinexor | 1.7 Liter per kilogram (L/kg) | Geometric Coefficient of Variation 24.1 |
| Selinexor (35 mg/m^2) | Apparent Volume of Distribution Uncorrected for Fraction Absorbed (Vd/F) of Selinexor | 2.0 Liter per kilogram (L/kg) | Geometric Coefficient of Variation 30.3 |
| Selinexor (40 mg/m^2) | Apparent Volume of Distribution Uncorrected for Fraction Absorbed (Vd/F) of Selinexor | 1.7 Liter per kilogram (L/kg) | Geometric Coefficient of Variation 29.1 |
| Selinexor (46 mg/m^2) | Apparent Volume of Distribution Uncorrected for Fraction Absorbed (Vd/F) of Selinexor | 1.8 Liter per kilogram (L/kg) | Geometric Coefficient of Variation 12.9 |
| Selinexor (55 mg/m^2) | Apparent Volume of Distribution Uncorrected for Fraction Absorbed (Vd/F) of Selinexor | 1.9 Liter per kilogram (L/kg) | Geometric Coefficient of Variation 27.9 |
| Selinexor (60 mg/m^2) | Apparent Volume of Distribution Uncorrected for Fraction Absorbed (Vd/F) of Selinexor | 1.6 Liter per kilogram (L/kg) | Geometric Coefficient of Variation 23 |
| Selinexor (70 mg/m^2) | Apparent Volume of Distribution Uncorrected for Fraction Absorbed (Vd/F) of Selinexor | 1.7 Liter per kilogram (L/kg) | Geometric Coefficient of Variation 13.4 |
| Selinexor (80 mg/m^2) | Apparent Volume of Distribution Uncorrected for Fraction Absorbed (Vd/F) of Selinexor | NA Liter per kilogram (L/kg) | — |
Secondary
Area Under the Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Selinexor
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Diffuse Large B-cell Lymphoma (DLBCL) | Area Under the Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Selinexor | 348 ng*h/mL | — |
| Non-Hodgkin Lymphoma (NHL) Excluding DLBCL | Area Under the Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Selinexor | 733 ng*h/mL | — |
| Multiple Myeloma (MM) | Area Under the Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Selinexor | 1529 ng*h/mL | Geometric Coefficient of Variation 18.7 |
| Acute Myeloid Leukemia (AML) | Area Under the Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Selinexor | 1867 ng*h/mL | Geometric Coefficient of Variation 23.6 |
| Other Hematological Malignancies (ALL, CML and CLL) | Area Under the Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Selinexor | 2645 ng*h/mL | Geometric Coefficient of Variation 1111 |
| Selinexor (30 mg/m^2) | Area Under the Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Selinexor | 3513 ng*h/mL | Geometric Coefficient of Variation 26 |
| Selinexor (35 mg/m^2) | Area Under the Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Selinexor | 3948 ng*h/mL | Geometric Coefficient of Variation 28.6 |
| Selinexor (40 mg/m^2) | Area Under the Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Selinexor | 4552 ng*h/mL | Geometric Coefficient of Variation 23.7 |
| Selinexor (46 mg/m^2) | Area Under the Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Selinexor | 5284 ng*h/mL | Geometric Coefficient of Variation 21 |
| Selinexor (55 mg/m^2) | Area Under the Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Selinexor | 6089 ng*h/mL | Geometric Coefficient of Variation 32.3 |
| Selinexor (60 mg/m^2) | Area Under the Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Selinexor | 6964 ng*h/mL | Geometric Coefficient of Variation 12.2 |
| Selinexor (70 mg/m^2) | Area Under the Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Selinexor | 7803 ng*h/mL | Geometric Coefficient of Variation 8.5 |
| Selinexor (80 mg/m^2) | Area Under the Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Selinexor | NA ng*h/mL | — |
Secondary
Area Under the Concentration-Time Curve From Time 0 to t (AUC0-t) of Selinexor
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Diffuse Large B-cell Lymphoma (DLBCL) | Area Under the Concentration-Time Curve From Time 0 to t (AUC0-t) of Selinexor | 331 nanogram* hours per milliliter | — |
| Non-Hodgkin Lymphoma (NHL) Excluding DLBCL | Area Under the Concentration-Time Curve From Time 0 to t (AUC0-t) of Selinexor | 564 nanogram* hours per milliliter | Geometric Coefficient of Variation 41.9 |
| Multiple Myeloma (MM) | Area Under the Concentration-Time Curve From Time 0 to t (AUC0-t) of Selinexor | 1459 nanogram* hours per milliliter | Geometric Coefficient of Variation 20.5 |
| Acute Myeloid Leukemia (AML) | Area Under the Concentration-Time Curve From Time 0 to t (AUC0-t) of Selinexor | 1829 nanogram* hours per milliliter | Geometric Coefficient of Variation 23.3 |
| Other Hematological Malignancies (ALL, CML and CLL) | Area Under the Concentration-Time Curve From Time 0 to t (AUC0-t) of Selinexor | 2774 nanogram* hours per milliliter | Geometric Coefficient of Variation 36.7 |
| Selinexor (30 mg/m^2) | Area Under the Concentration-Time Curve From Time 0 to t (AUC0-t) of Selinexor | 3461 nanogram* hours per milliliter | Geometric Coefficient of Variation 26.9 |
| Selinexor (35 mg/m^2) | Area Under the Concentration-Time Curve From Time 0 to t (AUC0-t) of Selinexor | 3901 nanogram* hours per milliliter | Geometric Coefficient of Variation 29.2 |
| Selinexor (40 mg/m^2) | Area Under the Concentration-Time Curve From Time 0 to t (AUC0-t) of Selinexor | 4481 nanogram* hours per milliliter | Geometric Coefficient of Variation 23.8 |
| Selinexor (46 mg/m^2) | Area Under the Concentration-Time Curve From Time 0 to t (AUC0-t) of Selinexor | 5228 nanogram* hours per milliliter | Geometric Coefficient of Variation 21.6 |
| Selinexor (55 mg/m^2) | Area Under the Concentration-Time Curve From Time 0 to t (AUC0-t) of Selinexor | 5601 nanogram* hours per milliliter | Geometric Coefficient of Variation 36.2 |
| Selinexor (60 mg/m^2) | Area Under the Concentration-Time Curve From Time 0 to t (AUC0-t) of Selinexor | 5282 nanogram* hours per milliliter | Geometric Coefficient of Variation 57.9 |
| Selinexor (70 mg/m^2) | Area Under the Concentration-Time Curve From Time 0 to t (AUC0-t) of Selinexor | 5466 nanogram* hours per milliliter | Geometric Coefficient of Variation 45.7 |
| Selinexor (80 mg/m^2) | Area Under the Concentration-Time Curve From Time 0 to t (AUC0-t) of Selinexor | 5544 nanogram* hours per milliliter | Geometric Coefficient of Variation 33.2 |
Secondary
Average Concentration From Time 0 to 24 Hours (Cavg0-24h) of Selinexor
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Diffuse Large B-cell Lymphoma (DLBCL) | Average Concentration From Time 0 to 24 Hours (Cavg0-24h) of Selinexor | 17.0 ng/mL | — |
| Non-Hodgkin Lymphoma (NHL) Excluding DLBCL | Average Concentration From Time 0 to 24 Hours (Cavg0-24h) of Selinexor | 20.3 ng/mL | Geometric Coefficient of Variation 94.8 |
| Multiple Myeloma (MM) | Average Concentration From Time 0 to 24 Hours (Cavg0-24h) of Selinexor | 61.8 ng/mL | Geometric Coefficient of Variation 39.9 |
| Acute Myeloid Leukemia (AML) | Average Concentration From Time 0 to 24 Hours (Cavg0-24h) of Selinexor | 79.0 ng/mL | Geometric Coefficient of Variation 61.8 |
| Other Hematological Malignancies (ALL, CML and CLL) | Average Concentration From Time 0 to 24 Hours (Cavg0-24h) of Selinexor | 108 ng/mL | Geometric Coefficient of Variation 46.8 |
| Selinexor (30 mg/m^2) | Average Concentration From Time 0 to 24 Hours (Cavg0-24h) of Selinexor | 160 ng/mL | Geometric Coefficient of Variation 38 |
| Selinexor (35 mg/m^2) | Average Concentration From Time 0 to 24 Hours (Cavg0-24h) of Selinexor | 168 ng/mL | Geometric Coefficient of Variation 54 |
| Selinexor (40 mg/m^2) | Average Concentration From Time 0 to 24 Hours (Cavg0-24h) of Selinexor | 163 ng/mL | Geometric Coefficient of Variation 29.2 |
| Selinexor (46 mg/m^2) | Average Concentration From Time 0 to 24 Hours (Cavg0-24h) of Selinexor | 297 ng/mL | Geometric Coefficient of Variation 26.3 |
| Selinexor (55 mg/m^2) | Average Concentration From Time 0 to 24 Hours (Cavg0-24h) of Selinexor | 208 ng/mL | Geometric Coefficient of Variation 19.1 |
| Selinexor (60 mg/m^2) | Average Concentration From Time 0 to 24 Hours (Cavg0-24h) of Selinexor | 337 ng/mL | Geometric Coefficient of Variation 4.2 |
| Selinexor (70 mg/m^2) | Average Concentration From Time 0 to 24 Hours (Cavg0-24h) of Selinexor | 353 ng/mL | Geometric Coefficient of Variation 26.2 |
| Selinexor (80 mg/m^2) | Average Concentration From Time 0 to 24 Hours (Cavg0-24h) of Selinexor | NA ng/mL | — |
Secondary
Duration of at Least Stable Disease
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)
Population: Efficacy analysis included all participants registered to the study who had either completed 1 cycle of treatment or discontinued treatment prior to completing the first cycle due to documented disease progression, death related to disease, or treatment-related toxicity.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Diffuse Large B-cell Lymphoma (DLBCL) | Duration of at Least Stable Disease | 52 Days |
| Non-Hodgkin Lymphoma (NHL) Excluding DLBCL | Duration of at Least Stable Disease | 114 Days |
| Multiple Myeloma (MM) | Duration of at Least Stable Disease | 57 Days |
| Acute Myeloid Leukemia (AML) | Duration of at Least Stable Disease | 80 Days |
| Other Hematological Malignancies (ALL, CML and CLL) | Duration of at Least Stable Disease | 64 Days |
Secondary
Duration of Response
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)
Population: Efficacy analysis included all participants who had either completed 1 cycle of treatment or discontinued treatment prior to completing the first cycle due to documented disease progression, death related to disease, or treatment-related toxicity. Here 'Overall Number of Participants Analyzed' signifies number of participants analyzed for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Diffuse Large B-cell Lymphoma (DLBCL) | Duration of Response | 335.5 Days |
| Non-Hodgkin Lymphoma (NHL) Excluding DLBCL | Duration of Response | 251 Days |
| Multiple Myeloma (MM) | Duration of Response | 180 Days |
| Acute Myeloid Leukemia (AML) | Duration of Response | 76 Days |
| Other Hematological Malignancies (ALL, CML and CLL) | Duration of Response | NA Days |
Secondary
Maximum Observed Plasma Concentration (Cmax) of Selinexor
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Diffuse Large B-cell Lymphoma (DLBCL) | Maximum Observed Plasma Concentration (Cmax) of Selinexor | 49.0 nanogram per milliliter (ng/mL) | — |
| Non-Hodgkin Lymphoma (NHL) Excluding DLBCL | Maximum Observed Plasma Concentration (Cmax) of Selinexor | 50.0 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 61.1 |
| Multiple Myeloma (MM) | Maximum Observed Plasma Concentration (Cmax) of Selinexor | 149 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 37.6 |
| Acute Myeloid Leukemia (AML) | Maximum Observed Plasma Concentration (Cmax) of Selinexor | 205 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 46.8 |
| Other Hematological Malignancies (ALL, CML and CLL) | Maximum Observed Plasma Concentration (Cmax) of Selinexor | 262 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 37.5 |
| Selinexor (30 mg/m^2) | Maximum Observed Plasma Concentration (Cmax) of Selinexor | 387 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 37.1 |
| Selinexor (35 mg/m^2) | Maximum Observed Plasma Concentration (Cmax) of Selinexor | 407 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 44.4 |
| Selinexor (40 mg/m^2) | Maximum Observed Plasma Concentration (Cmax) of Selinexor | 416 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 36.6 |
| Selinexor (46 mg/m^2) | Maximum Observed Plasma Concentration (Cmax) of Selinexor | 670 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 18.5 |
| Selinexor (55 mg/m^2) | Maximum Observed Plasma Concentration (Cmax) of Selinexor | 583 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 41.4 |
| Selinexor (60 mg/m^2) | Maximum Observed Plasma Concentration (Cmax) of Selinexor | 668 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 33.2 |
| Selinexor (70 mg/m^2) | Maximum Observed Plasma Concentration (Cmax) of Selinexor | 800 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 32.4 |
| Selinexor (80 mg/m^2) | Maximum Observed Plasma Concentration (Cmax) of Selinexor | 1068 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 49.3 |
Secondary
Number of Participants With Overall Response of Selinexor
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)
Population: Efficacy analysis included all participants registered to the study who had either completed 1 cycle of treatment or discontinued treatment prior to completing the first cycle due to documented disease progression, death related to disease, or treatment-related toxicity.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Diffuse Large B-cell Lymphoma (DLBCL) | Number of Participants With Overall Response of Selinexor | Partial remission | 0 participants |
| Diffuse Large B-cell Lymphoma (DLBCL) | Number of Participants With Overall Response of Selinexor | Complete hematological response | 0 participants |
| Diffuse Large B-cell Lymphoma (DLBCL) | Number of Participants With Overall Response of Selinexor | Complete response | 5 participants |
| Diffuse Large B-cell Lymphoma (DLBCL) | Number of Participants With Overall Response of Selinexor | Partial response | 7 participants |
| Diffuse Large B-cell Lymphoma (DLBCL) | Number of Participants With Overall Response of Selinexor | Morphologic complete remission | 0 participants |
| Diffuse Large B-cell Lymphoma (DLBCL) | Number of Participants With Overall Response of Selinexor | Complete cytogenetic response | 0 participants |
| Non-Hodgkin Lymphoma (NHL) Excluding DLBCL | Number of Participants With Overall Response of Selinexor | Morphologic complete remission | 0 participants |
| Non-Hodgkin Lymphoma (NHL) Excluding DLBCL | Number of Participants With Overall Response of Selinexor | Complete response | 1 participants |
| Non-Hodgkin Lymphoma (NHL) Excluding DLBCL | Number of Participants With Overall Response of Selinexor | Partial remission | 0 participants |
| Non-Hodgkin Lymphoma (NHL) Excluding DLBCL | Number of Participants With Overall Response of Selinexor | Partial response | 8 participants |
| Non-Hodgkin Lymphoma (NHL) Excluding DLBCL | Number of Participants With Overall Response of Selinexor | Complete cytogenetic response | 0 participants |
| Non-Hodgkin Lymphoma (NHL) Excluding DLBCL | Number of Participants With Overall Response of Selinexor | Complete hematological response | 0 participants |
| Multiple Myeloma (MM) | Number of Participants With Overall Response of Selinexor | Partial remission | 0 participants |
| Multiple Myeloma (MM) | Number of Participants With Overall Response of Selinexor | Complete cytogenetic response | 0 participants |
| Multiple Myeloma (MM) | Number of Participants With Overall Response of Selinexor | Complete hematological response | 0 participants |
| Multiple Myeloma (MM) | Number of Participants With Overall Response of Selinexor | Partial response | 6 participants |
| Multiple Myeloma (MM) | Number of Participants With Overall Response of Selinexor | Morphologic complete remission | 0 participants |
| Multiple Myeloma (MM) | Number of Participants With Overall Response of Selinexor | Complete response | 0 participants |
| Acute Myeloid Leukemia (AML) | Number of Participants With Overall Response of Selinexor | Complete response | 0 participants |
| Acute Myeloid Leukemia (AML) | Number of Participants With Overall Response of Selinexor | Partial response | 0 participants |
| Acute Myeloid Leukemia (AML) | Number of Participants With Overall Response of Selinexor | Morphologic complete remission | 4 participants |
| Acute Myeloid Leukemia (AML) | Number of Participants With Overall Response of Selinexor | Partial remission | 3 participants |
| Acute Myeloid Leukemia (AML) | Number of Participants With Overall Response of Selinexor | Complete cytogenetic response | 0 participants |
| Acute Myeloid Leukemia (AML) | Number of Participants With Overall Response of Selinexor | Complete hematological response | 0 participants |
| Other Hematological Malignancies (ALL, CML and CLL) | Number of Participants With Overall Response of Selinexor | Complete cytogenetic response | 0 participants |
| Other Hematological Malignancies (ALL, CML and CLL) | Number of Participants With Overall Response of Selinexor | Morphologic complete remission | 0 participants |
| Other Hematological Malignancies (ALL, CML and CLL) | Number of Participants With Overall Response of Selinexor | Partial response | 0 participants |
| Other Hematological Malignancies (ALL, CML and CLL) | Number of Participants With Overall Response of Selinexor | Complete response | 0 participants |
| Other Hematological Malignancies (ALL, CML and CLL) | Number of Participants With Overall Response of Selinexor | Partial remission | 1 participants |
| Other Hematological Malignancies (ALL, CML and CLL) | Number of Participants With Overall Response of Selinexor | Complete hematological response | 0 participants |
Secondary
Overall Survival
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)
Population: Efficacy analysis included all participants registered to the study who had either completed 1 cycle of treatment or discontinued treatment prior to completing the first cycle due to documented disease progression, death related to disease, or treatment-related toxicity.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Diffuse Large B-cell Lymphoma (DLBCL) | Overall Survival | 138 Days |
| Non-Hodgkin Lymphoma (NHL) Excluding DLBCL | Overall Survival | 423 Days |
| Multiple Myeloma (MM) | Overall Survival | 366 Days |
| Acute Myeloid Leukemia (AML) | Overall Survival | 76 Days |
| Other Hematological Malignancies (ALL, CML and CLL) | Overall Survival | 82 Days |
Secondary
Progression-free Survival
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)
Population: Efficacy analysis included all participants registered to the study who had either completed 1 cycle of treatment or discontinued treatment prior to completing the first cycle due to documented disease progression, death related to disease, or treatment-related toxicity.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Diffuse Large B-cell Lymphoma (DLBCL) | Progression-free Survival | 47 Days |
| Non-Hodgkin Lymphoma (NHL) Excluding DLBCL | Progression-free Survival | 110 Days |
| Multiple Myeloma (MM) | Progression-free Survival | 57 Days |
| Acute Myeloid Leukemia (AML) | Progression-free Survival | 44 Days |
| Other Hematological Malignancies (ALL, CML and CLL) | Progression-free Survival | 57 Days |
Secondary
Terminal Half-Life (t½) of Selinexor
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
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Diffuse Large B-cell Lymphoma (DLBCL) | Terminal Half-Life (t½) of Selinexor | NA hour |
| Non-Hodgkin Lymphoma (NHL) Excluding DLBCL | Terminal Half-Life (t½) of Selinexor | NA hour |
| Multiple Myeloma (MM) | Terminal Half-Life (t½) of Selinexor | 6.2 hour |
| Acute Myeloid Leukemia (AML) | Terminal Half-Life (t½) of Selinexor | 6.1 hour |
| Other Hematological Malignancies (ALL, CML and CLL) | Terminal Half-Life (t½) of Selinexor | 6.9 hour |
| Selinexor (30 mg/m^2) | Terminal Half-Life (t½) of Selinexor | 5.8 hour |
| Selinexor (35 mg/m^2) | Terminal Half-Life (t½) of Selinexor | 6.2 hour |
| Selinexor (40 mg/m^2) | Terminal Half-Life (t½) of Selinexor | 4.8 hour |
| Selinexor (46 mg/m^2) | Terminal Half-Life (t½) of Selinexor | 5.7 hour |
| Selinexor (55 mg/m^2) | Terminal Half-Life (t½) of Selinexor | 6.6 hour |
| Selinexor (60 mg/m^2) | Terminal Half-Life (t½) of Selinexor | 5.9 hour |
| Selinexor (70 mg/m^2) | Terminal Half-Life (t½) of Selinexor | 5.2 hour |
| Selinexor (80 mg/m^2) | Terminal Half-Life (t½) of Selinexor | NA hour |
Secondary
Time to Maximum Observed Concentration (Tmax) of Selinexor
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
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Diffuse Large B-cell Lymphoma (DLBCL) | Time to Maximum Observed Concentration (Tmax) of Selinexor | NA hour |
| Non-Hodgkin Lymphoma (NHL) Excluding DLBCL | Time to Maximum Observed Concentration (Tmax) of Selinexor | 4.0 hour |
| Multiple Myeloma (MM) | Time to Maximum Observed Concentration (Tmax) of Selinexor | 3.0 hour |
| Acute Myeloid Leukemia (AML) | Time to Maximum Observed Concentration (Tmax) of Selinexor | 2.08 hour |
| Other Hematological Malignancies (ALL, CML and CLL) | Time to Maximum Observed Concentration (Tmax) of Selinexor | 2.0 hour |
| Selinexor (30 mg/m^2) | Time to Maximum Observed Concentration (Tmax) of Selinexor | 2.0 hour |
| Selinexor (35 mg/m^2) | Time to Maximum Observed Concentration (Tmax) of Selinexor | 2.0 hour |
| Selinexor (40 mg/m^2) | Time to Maximum Observed Concentration (Tmax) of Selinexor | 4.0 hour |
| Selinexor (46 mg/m^2) | Time to Maximum Observed Concentration (Tmax) of Selinexor | 2.0 hour |
| Selinexor (55 mg/m^2) | Time to Maximum Observed Concentration (Tmax) of Selinexor | 2.9 hour |
| Selinexor (60 mg/m^2) | Time to Maximum Observed Concentration (Tmax) of Selinexor | 1.9 hour |
| Selinexor (70 mg/m^2) | Time to Maximum Observed Concentration (Tmax) of Selinexor | 2.0 hour |
| Selinexor (80 mg/m^2) | Time to Maximum Observed Concentration (Tmax) of Selinexor | 2.0 hour |