Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Symptoms and General Pathology

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Lymphoma

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Lymphoma, T-Cell

Lymphoma, T-Cell, Peripheral

Hematologic Neoplasms

Leukemia, Myeloid

Leukemia, Lymphocytic, Chronic, B-Cell

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Lymphoma, T-Cell, Cutaneous

Waldenstrom Macroglobulinemia

Hematologic Diseases

Myeloid Leukemia

Lymphosarcoma

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Peripheral T-cell Lymphoma

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

Chronic Myeloid Leukemia

Acute Graft Versus Host Disease

Cutaneous T-cell Lymphoma

KPT-330

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.

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

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

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 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.

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

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

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

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

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

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

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

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.

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 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 (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 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 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.

Karyopharm Therapeutics Inc

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.

Diffuse Large B-cell Lymphoma (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.

Non-Hodgkin Lymphoma (NHL) Excluding DLBCL

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.

Multiple Myeloma (MM)

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.

Acute Myeloid Leukemia (AML)

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.

Other Hematological Malignancies (ALL, CML and CLL)

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

White

Black

Asian

Native Hawaiian or Pacific Islander

American Indian or Alaskan Native

Other

Unknown/Not Reported

Race/Ethnicity, Customized

Safety population consisted of all participants who received at least 1 dose of selinexor.

Jatin Shah, MD

At Least One TEAE

At Least One Serious TEAE

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)

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.

Advanced Hematological Malignancies.

Efficacy analysis set included all participants who had either completed 1 cycle of treatment or discontinued treatment prior to completing the first cycle due to documented progressive disease (PD), death related to disease, or treatment-related toxicity. Here, data was not planned and analyzed based on individual specific disease, hence overall data was analyzed for this outcome measure.

Recommended Phase 2 Dose (RP2D) of Selinexor

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.

Selinexor (3 mg/m^2)

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.

Selinexor (6 mg/m^2)

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.

Selinexor (12 mg/m^2)

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.

Selinexor (16.8 mg/m^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.

Selinexor (23 mg/m^2)

Participants received selinexor dose of 30 mg/m\^2 orally at Cycle 1, on Day 1, 3, 4, 8, 10, 15 and 17 in schedule 3, 5 and 9.

Selinexor (30 mg/m^2)

Participants received selinexor dose of 35 mg/m\^2 orally at Cycle 1, on Day 1 and 3 in schedule 6.

Selinexor (35 mg/m^2)

Participants received selinexor dose of 40 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, 17 followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 8 and 11.

Selinexor (40 mg/m^2)

Participants received selinexor dose of 46 mg/m\^2 orally at Cycle 1, on Day 1 once-weekly in schedule 7.

Selinexor (46 mg/m^2)

Participants received selinexor dose of 55 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, and 10, followed by an 18-day treatment-free interval (Days 11 through 28) in schedule 10.

Selinexor (55 mg/m^2)

Participants received selinexor dose of 60 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, and 17, followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 11.

Selinexor (60 mg/m^2)

Participants received selinexor dose of 70 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, and 17, followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 11.

Selinexor (70 mg/m^2)

Participants received selinexor dose of 80 mg/m\^2 orally at Cycle 1, on Day 1, 3, 8, 10, 15, and 17, followed by an 11-day treatment-free interval (Days 18 through 28) in schedule 11.

Selinexor (80 mg/m^2)

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.

Maximum Observed Plasma Concentration (Cmax) of Selinexor

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.

Time to Maximum Observed Concentration (Tmax) of Selinexor

Average Concentration From Time 0 to 24 Hours (Cavg0-24h) of Selinexor

Area Under the Concentration-Time Curve From Time 0 to t (AUC0-t) of Selinexor

Area Under the Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Selinexor

Apparent Volume of Distribution Uncorrected for Fraction Absorbed (Vd/F) of Selinexor

Apparent Total Body Clearance, Uncorrected for Fraction Absorbed (Cl/F) of Selinexor

Terminal Half-Life (t½) of Selinexor

Complete response

Partial response

Morphologic complete remission

Partial remission

Complete cytogenetic response

Complete hematological response

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.

Number of Participants With Overall Response of Selinexor

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.

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

Trial Identification

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Interventions

Study Description

Keywords

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