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Selinexor Treatment of Refractory Myeloma (STORM)

Primary Purpose

Multiple Myeloma

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Selinexor

Dexamethasone

About this trial

This is an interventional treatment trial for Multiple Myeloma focused on measuring Multiple myeloma, Karyopharm, KPT-330, Selinexor, Refractory, Bortezomib, Carfilzomib, Lenalidomide, Pomalidomide, Dexamethasone, STORM, Daratumumab

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Measurable MM based on modified IMWG guidelines. Defined by at least one of the following:

Serum M-protein ≥ 0.5 g/dL by serum electrophoresis (SPEP) or for IgA myeloma, by quantitative IgA
Urinary M-protein excretion ≥ 200 mg/24 hours
Free Light Chain (FLC) ≥ 100 mg/L, provided that the FLC ratio is abnormal
If serum protein electrophoresis is felt to be unreliable for routine M-protein measurement, then quantitative Ig levels by nephelometry or turbidimetry are acceptable
- Must have previously received ≥ 3 anti-MM regimens including: an alkylating agent, lenalidomide, pomalidomide, bortezomib, carfilzomib, daratumumab, and a glucocorticoid. There is no upper limit on the number of prior therapies provided that all other inclusion/exclusion criteria are met.
- MM refractory to previous treatment with one or more glucocorticoids, parenteral PI (i.e., bortezomib and/or carfilzomib), IMiD (i.e., lenalidomide and/or pomalidomide), and the anti-CD38 mAb, daratumumab. Refractory is defined as ≤ 25% response to therapy, or progression during therapy or progression within 60 days after completion of therapy.

Exclusion Criteria:

Active smoldering MM.
Active plasma cell leukemia.
Documented systemic amyloid light chain amyloidosis.
Active CNS MM.

Sites / Locations

University of Alabama
Mayo Clinic (AZ)
City of Hope
Jonnsson Comprehensive Cancer Center / University of Los Angeles
Smilow Cancer Hospital
University of Florida Health Cancer Center- Shands Cancer Center Hospital
Sylvester, University of Miami
H. Lee Moffitt Cancer Center Research Institute
Emory University / Winship Cancer Institute
Northside Hospital
Kaiser Permanente- Hawaii
University of Chicago Medicine
Indiana University Simon Cancer Center
University of Iowa Hospitals & Clinics
Norton Cancer Institute
Johns Hopkins Medicine
Tufts Medical Center
Massachusetts General Hospital
Dana Farber Cancer Institute
University of Michigan
Karmanos Cancer Institute / Wayne State University
Mayo Clinic Rochester
Washington University St. Louis
Hackensack University Medical Center / John Therurer Cancer Center
Valley Hospital
Roswell Park Cancer Institute
NYU Perlmutter Cancer Center
Mt Sinai NYC
Columbia University
UNC-Chapel Hill
Gabrail Cancer Center
Kaiser Permanente Northwest OR
Abramson Cancer Center of the University of Pennsylvania
Vanderbilt University Ingram Cancer Center
Baylor Sammons Cancer Center
Swedish Cancer Institute
University Hospital Krems, Department of Internal Medicine II
Salzburg Regional Hospital Müllner
Medical University Vienna, Department of Internal Medicine I
ZNA Stuivenberg
General Hospital Saint-Jan
Jules Bordet Institute
UCL Saint-Luc
University Hospital Ghent
University Hospital Leuven, Campus Gasthuisberg
UCL Mont-Godinne
Claude Huriez Hospital, Department of Blood Diseases
South Lyon Hospital Center, Department of Clinical Hematology
Brabois Adults Hospital
Nantes University Hospital Center
Hopital Saint-Antoine, Service d´Hematologie Clinique et Therapie Cellulaire
La Pitie-Salpetriere University Hospital, Department of Clinical Hematology
Necker Children's Hospital
BAG Oncology Gemeinschaftspraxis
University Hospital Freiburg, Department of Internal Medicine I
Universitätsklinikum Heidelberg Medizinische Klinik V
Universitätsklinikum des Saarlandes Klinik für Innere Medizin I
Universitätsmedizin Mainz
University hospital of Tuebingen, Internal Medicine II
Med. Klinik und Poliklinik II Universitätsklinikum
National & Kapodistrain University of Athens School of Medicine, Alexandra Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Part 1

Part 2

Arm Description

Participants with quad-exposed, double-class-refractory (i.e. previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, but not an anti-CD38 mab) and penta-exposed, triple-class-refractory multiple myeloma (MM) (i.e. previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, and daratumumab, and refractory to prior treatment with glucocorticoids, an immunomodulatory agent (IMiD), a proteasome inhibitor (PI), and the anti-CD38 mAb daratumumab) received, two dosing schedules (1) Selinexor 80 milligrams (mg) plus low-dose dexamethasone 20 mg (Sd) twice-weekly on Days 1 and 3 for 3 weeks of each 4-week cycle (2) Selinexor 80 mg plus low-dose dexamethasone 20 mg (Sd) twice-weekly continuously in 4-week cycles; until disease progression, death, or unacceptable toxicity (maximum duration of approximately 13 months).

Participants who previously had received more than 3 anti-MM regimens and had penta-exposed, triple class-refractory MM (i.e. previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, and daratumumab, and refractory to prior treatment with glucocorticoids, an IMiD, a PI, and the anti-CD38 mAb daratumumab) received, Selinexor 80 mg post oral (PO) plus low-dose dexamethasone 20 mg Sd twice-weekly on Days 1 and 3 until disease progression, death, or unacceptable toxicity (maximum duration of approximately 17 months).

Outcomes

Primary Outcome Measures

Part 2: Percentage of Participants With Overall Response Rate (ORR) Per International MyelomaWorking Group (IMWG) as Assessed by an Independent Review Committee (IRC)

IRC assessed ORR per 2016 IMWG criteria: Percentage of participants who experienced Partial response (PR): greater than or equal to (>=) 50 percent (%) reduction of serum M-Protein and reduction in 24-hour urinary M-protein by >= 90% or to lesser than (<) 200 mg per 24 hours; Very good partial response (VGPR): Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level < 100 mg per 24 hours; Complete response (CR): Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and lesser than or equal to (<=) 5% plasma cells in bone marrow; or stringent complete response (sCR): CR as defined+Normal free light chain (FLC) ratio+Absence of clonal cells in bone marrow biopsy by immunohistochemistry).

Secondary Outcome Measures

Part 1: Duration of Response (DoR) Per IMWG as Assessed by IRC

IRC assessed DoR per 2016 IMWG criteria: time (in months) from the first documentation of objective response (confirmed CR or PR) to the date of first documentation of progressive disease (PD) or death due to any cause. Partial response (PR): >= 50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by >= 90% or to < 200 mg per 24 hours; Complete response (CR): Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and <= 5% plasma cells in bone marrow; Progressive disease (PD): Increase of 25% from lowest confirmed response value in 1 or more of the following criteria: Serum M-protein with absolute increase of >= 0.5 gram per deciliter (g/dL); Serum M-protein increase >= 1 g/dL if the lowest M-component was >=5 g/dL; Urine M-protein (absolute increase must be >= 200 mg per 24 hours). Analysis was performed using Kaplan-Meier method.

Part 2: Duration of Response (DoR) Per IMWG as Assessed by an IRC

IRC assessed DoR per 2016 IMWG criteria: time (in months) from the first documentation of objective response (confirmed CR or PR) to the date of first documentation of progressive disease (PD) or death due to any cause. Partial response (PR): >= 50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by >= 90% or to < 200 mg per 24 hours; Complete response (CR): Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and <= 5% plasma cells in bone marrow; Progressive disease (PD): Increase of 25% from lowest confirmed response value in 1 or more of the following criteria: Serum M-protein with absolute increase of >= 0.5 g/dL; Serum M-protein increase >= 1 g/dL if the lowest M-component was >= 5 g/dL; Urine M-protein (absolute increase must be >= 200 mg per 24 hours). Analysis was performed using Kaplan-Meier method.

Part 1: Percentage of Participants With Clinical Benefit Rate (CBR) ) Per IMWG as Assessed by IRC

IRC assessed CBR per 2016 IMWG criteria: Percentage of participants with a confirmed minimal response (MR) or better (PR, VGPR, CR or sCR) before confirmed disease progression or initiating new MM treatment. Minimal response (MR): >= 25% but < 49% reduction of serum M-protein and reduction in 24-hour urinary M-protein by 50-89%. Partial response (PR): >= 50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by >= 90% or to < 200 mg per 24 hours; Very good partial response (VGPR): Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level < 100 mg per 24 hours; Complete response (CR): Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and <= 5% plasma cells in bone marrow; or stringent complete response (sCR): CR as defined+Normal free light chain (FLC) ratio+Absence of clonal cells by immunohistochemistry).

Part 2: Percentage of Participants With Clinical Benefit Rate (CBR) Per IMWG as Assessed by IRC

Part 1: Duration of Clinical Benefit Per IMWG as Assessed by IRC

IRC assessed duration of clinical benefit per 2016 IMWG criteria: Duration from first response (at least MR) to time of IRC-determined PD or death due to disease progression, whichever occurs first. Minimal response (MR): >= 25% but < 49% reduction of serum M-protein and reduction in 24-hour urinary M-protein by 50-89%. Progressive disease (PD): Increase of 25% from lowest confirmed response value in 1 or more of the following criteria: Serum M-protein with absolute increase of >= 0.5 g/dL; Serum M-protein increase >= 1 g/dL if the lowest M-component was >=5 g/dL; Urinary M-protein (absolute increase must be >= 200 mg per 24 hours). Analysis was performed using Kaplan-Meier method.

Part 2: Duration of Clinical Benefit Per IMWG as Assessed by IRC

Part 2: Disease Control Rate (DCR)

DCR was defined as the percentage of participants who achieved stable disease (SD) or better (MR, PR, VGPR, CR, sCR) for a minimum of 12 weeks. Stable disease (SD): Not recommended for use as an indicator of response; stability of disease was best described by providing the time to progression (TTP) estimates. MR: >= 25% but < 49% reduction of serum M-protein and reduction in 24-hour urinary M-protein by 50-89%. PR: >=50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by >= 90% or to < 200 mg per 24 hours; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level < 100 mg per 24 hours; CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and <= 5% plasma cells in bone marrow; or sCR: CR as defined+Normal FLC ratio+Absence of clonal cells by immunohistochemistry).

Part 1: Progression Free Survival (PFS) Per IMWG as Assessed by IRC

IRC assessed PFS per 2016 IMWG criteria: Duration from start of study treatment until IRC-determined progressive disease (PD) or death from any cause, whichever occurred first. Progressive disease (PD): Increase of 25% from lowest confirmed response value in 1 or more of the following criteria: Serum M-protein with absolute increase of >= 0.5 g/dL; Serum M-protein increase >=1 g/dL if the lowest M-component was >= 5 g/dL; Urinary M-protein (absolute increase must be >= 200 mg/24 hours). Analysis was performed using Kaplan-Meier method.

Part 2: Progression Free Survival (PFS) Per IMWG as Assessed by IRC

Part 1: Time to Progression (TTP) Per IMWG as Assessed by IRC

IRC assessed TTP per 2016 IMWG criteria: Duration from start of study treatment until PD or death due to PD (per IRC), whichever occurred first. Progressive disease (PD): Increase of 25% from lowest confirmed response value in 1 or more of the following criteria: Serum M-protein with absolute increase of >= 0.5 g/dL; Serum M-protein increase >=1 g/dL if the lowest M-component was >= 5 g/dL; Urinary M-protein (absolute increase must be >= 200 mg/24 hours). Analysis was performed using Kaplan-Meier method.

Part 2: Time to Progression (TTP) Per IMWG as Assessed by IRC

Part 1: Time to Next Treatment (TTNT)

TTNT was defined as the duration from start of study treatment to start of next anti-MM treatment or death due to disease progression, whichever occurred first. Analysis was performed using Kaplan-Meier method.

Part 2: Time to Next Treatment (TTNT)

Part 1: Overall Survival (OS)

OS was defined as the duration (in months) from start of study treatment to death from any cause. Participants last known to be alive were censored at the date of discontinuation from the study, or database cut date, whichever was earlier. Analysis was performed using Kaplan-Meier method.

Part 2: Overall Survival (OS)

Part 2: Change From Baseline in Health-related Quality of Life (HRQL) Score Based on Functional Assessment of Cancer Therapy - Multiple Myeloma (FACT-MM) Questionnaire

FACT-MM combines the general version of the FACT (FACT-G) with a MM-specific sub-scale (14 items). The sub-scales for the FACT-G are Physical Well-Being (7 items), Social/Family Well-Being (7 items), Emotional Well-Being (6 items), and Functional Well-Being (7 items). The trial outcomes index (TOI); total of 41 items) is the primary measurement of interest, comprised of the Physical and Functional sub-scales plus the MM-specific sub-scale. Each item is rated on a 5-point Likert scale, ranging from 0 ("Not at all") to 4 ("Very much"), therefore the TOI has a score ranging from 0 to 120. Higher scores indicated improvement in well being.

Number of Participants With Treatment-Emergent Adverse Events (TEAE) of Grade 3/4, Graded Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. As per NCI-CTCAE version 4.03, Grade 1: asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. Treatment-emergent events are events between first dose of study drug and up to last dose of study treatment + 30 days (inclusive) that were absent before treatment or that worsened relative to pre-treatment state.

Number of Participants With Treatment-Emergent Treatment-Related Adverse Events (TEAEs) of Grade 3/4, Graded Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. As per NCI-CTCAE version 4.03, Grade 1: asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. A treatment related AE was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event had a causal relationship with the treatment or usage.

Apparent Clearance (CL/F) of Selinexor in Plasma

CL/F of selinexor in plasma was reported.

Volume of Distribution (V/F) of Selinexor in Plasma

Vz/F of selinexor in plasma was reported.

Full Information

NCT ID

NCT02336815

First Posted

January 8, 2015

Last Updated

January 24, 2023

Sponsor

Karyopharm Therapeutics Inc

1. Study Identification

Unique Protocol Identification Number

NCT02336815

Brief Title

Selinexor Treatment of Refractory Myeloma

Acronym

STORM

Official Title

A Phase 2b, Open-Label, Single-Arm Study of Selinexor (KPT-330) Plus Low-Dose Dexamethasone (Sd) in Patients With Multiple Myeloma Previously Treated With Lenalidomide, Pomalidomide, Bortezomib, Carfilzomib, and an Anti-CD38 Monoclonal Antibody (mAb) Daratumumab, and Refractory to Prior Treatment With Glucocorticoids, an Immunomodulatory Agent, a Proteasome Inhibitor, and an the Anti-CD38 mAb Daratumumab

Study Type

Interventional

2. Study Status

Record Verification Date

January 2023

Overall Recruitment Status

Completed

Study Start Date

May 26, 2015 (Actual)

Primary Completion Date

July 26, 2019 (Actual)

Study Completion Date

July 26, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Karyopharm Therapeutics Inc

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This is a Phase 2b, single-arm, open-label, multicenter study of selinexor 80 mg plus dexamethasone 20 mg (Sd) dosed twice weekly in four-week cycles, in patients with penta-refractory MM (Parts 1 and 2) or quad refractory MM (Part 1 only).

Detailed Description

This is a Phase 2b, single-arm, open-label, multicenter study of selinexor 80 mg plus dexamethasone 20 mg (Sd), both dosed twice weekly in each four-week cycle, in patients with MM previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, and daratumumab and refractory to prior treatment with glucocorticoids, an immunomodulatory agent (IMiD), a proteasome inhibitor (PI), and daratumumab. This study consists of two parts: Part 1 enrolled patients with both quad-refractory MM and penta-refractory MM. Part 2 will enroll patients with penta-refractory MM only.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Multiple Myeloma

Keywords

Multiple myeloma, Karyopharm, KPT-330, Selinexor, Refractory, Bortezomib, Carfilzomib, Lenalidomide, Pomalidomide, Dexamethasone, STORM, Daratumumab

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

202 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Part 1

Arm Type

Experimental

Arm Description

Arm Title

Part 2

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Selinexor

Other Intervention Name(s)

KPT-330

Intervention Description

Fixed oral dose of 80 mg twice weekly (e.g., Monday and Wednesday or Tuesday and Thursday, etc.)

Intervention Type

Drug

Intervention Name(s)

Dexamethasone

Intervention Description

20 mg was given with each dose of Selinexor.

Primary Outcome Measure Information:

Title

Part 2: Percentage of Participants With Overall Response Rate (ORR) Per International MyelomaWorking Group (IMWG) as Assessed by an Independent Review Committee (IRC)

Description

Time Frame

Baseline until disease progression/discontinuation from the study, or death, whichever occurred first (maximum duration of 17 months)

Secondary Outcome Measure Information:

Title

Part 1: Duration of Response (DoR) Per IMWG as Assessed by IRC

Description

Time Frame

First response subsequently confirmed to disease progression/discontinuation from the study, or death, whichever occurred first (maximum duration of 13 months)

Title

Part 2: Duration of Response (DoR) Per IMWG as Assessed by an IRC

Description

IRC assessed DoR per 2016 IMWG criteria: time (in months) from the first documentation of objective response (confirmed CR or PR) to the date of first documentation of progressive disease (PD) or death due to any cause. Partial response (PR): >= 50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by >= 90% or to < 200 mg per 24 hours; Complete response (CR): Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and <= 5% plasma cells in bone marrow; Progressive disease (PD): Increase of 25% from lowest confirmed response value in 1 or more of the following criteria: Serum M-protein with absolute increase of >= 0.5 g/dL; Serum M-protein increase >= 1 g/dL if the lowest M-component was >= 5 g/dL; Urine M-protein (absolute increase must be >= 200 mg per 24 hours). Analysis was performed using Kaplan-Meier method.

Time Frame

First response subsequently confirmed to disease progression/discontinuation from the study, or death, whichever occurred first (maximum duration of 17 months)

Title

Part 1: Percentage of Participants With Clinical Benefit Rate (CBR) ) Per IMWG as Assessed by IRC

Description

Time Frame

Baseline up to a maximum of 13 months

Title

Part 2: Percentage of Participants With Clinical Benefit Rate (CBR) Per IMWG as Assessed by IRC

Description

Time Frame

Baseline up to a maximum of 17 months

Title

Part 1: Duration of Clinical Benefit Per IMWG as Assessed by IRC

Description

Time Frame

First response subsequently confirmed to disease progression, or death, whichever occurred first (maximum duration of 13 months)

Title

Part 2: Duration of Clinical Benefit Per IMWG as Assessed by IRC

Description

Time Frame

First response subsequently confirmed to disease progression, or death, whichever occurred first (maximum duration of 17 months)

Title

Part 2: Disease Control Rate (DCR)

Description

Time Frame

Every 12 weeks until progressive disease or death due to any cause, up to 17 months

Title

Part 1: Progression Free Survival (PFS) Per IMWG as Assessed by IRC

Description

Time Frame

From start of study treatment to progression of disease or discontinuation from the study or death, whichever occurred first (maximum duration of 13 months)

Title

Part 2: Progression Free Survival (PFS) Per IMWG as Assessed by IRC

Description

Time Frame

From start of study treatment to progression of disease or discontinuation from the study or death, whichever occurred first (maximum duration of 17 months)

Title

Part 1: Time to Progression (TTP) Per IMWG as Assessed by IRC

Description

Time Frame

From start of study treatment to progression of disease or death, whichever occurred first (maximum duration of 13 months)

Title

Part 2: Time to Progression (TTP) Per IMWG as Assessed by IRC

Description

Time Frame

From start of study treatment to progression of disease or death, whichever occurred first (maximum duration of 17 months)

Title

Part 1: Time to Next Treatment (TTNT)

Description

Time Frame

From start of study treatment to start of next anti-MM treatment or death due to disease progression, whichever occurs first (maximum duration of 13 months)

Title

Part 2: Time to Next Treatment (TTNT)

Description

Time Frame

From start of study treatment to start of next anti-MM treatment or death due to disease progression, whichever occurs first (maximum duration of 17 months)

Title

Part 1: Overall Survival (OS)

Description

Time Frame

From start of study treatment to death (maximum duration of 13 months)

Title

Part 2: Overall Survival (OS)

Description

Time Frame

From start of study treatment to death (maximum duration of 17 months)

Title

Part 2: Change From Baseline in Health-related Quality of Life (HRQL) Score Based on Functional Assessment of Cancer Therapy - Multiple Myeloma (FACT-MM) Questionnaire

Description

Time Frame

Baseline, Day 1 of Cycle 2 to Cycle 20 (up to a maximum of 17 months)

Title

Number of Participants With Treatment-Emergent Adverse Events (TEAE) of Grade 3/4, Graded Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03

Description

Time Frame

Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)

Title

Number of Participants With Treatment-Emergent Treatment-Related Adverse Events (TEAEs) of Grade 3/4, Graded Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03

Description

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. As per NCI-CTCAE version 4.03, Grade 1: asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. A treatment related AE was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event had a causal relationship with the treatment or usage.

Time Frame

Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)

Title

Apparent Clearance (CL/F) of Selinexor in Plasma

Description

CL/F of selinexor in plasma was reported.

Time Frame

Cycle 1: Day 1: Pre-dose, 1, 2 and 4 hours post-dose; Day 8 and 15: Pre-dose and 1 hour post-dose; Cycle 2: Day 1: Predose, 1, 2 and 4 hours post-dose

Title

Volume of Distribution (V/F) of Selinexor in Plasma

Description

Vz/F of selinexor in plasma was reported.

Time Frame

Cycle 1: Day 1: Pre-dose, 1, 2 and 4 hours post-dose; Day 8 and 15: Pre-dose and 1 hour post-dose; Cycle 2: Day 1: Predose, 1, 2 and 4 hours post-dose

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Measurable MM based on modified IMWG guidelines. Defined by at least one of the following: Serum M-protein ≥ 0.5 g/dL by serum electrophoresis (SPEP) or for IgA myeloma, by quantitative IgA Urinary M-protein excretion ≥ 200 mg/24 hours Free Light Chain (FLC) ≥ 100 mg/L, provided that the FLC ratio is abnormal If serum protein electrophoresis is felt to be unreliable for routine M-protein measurement, then quantitative Ig levels by nephelometry or turbidimetry are acceptable Must have previously received ≥ 3 anti-MM regimens including: an alkylating agent, lenalidomide, pomalidomide, bortezomib, carfilzomib, daratumumab, and a glucocorticoid. There is no upper limit on the number of prior therapies provided that all other inclusion/exclusion criteria are met. MM refractory to previous treatment with one or more glucocorticoids, parenteral PI (i.e., bortezomib and/or carfilzomib), IMiD (i.e., lenalidomide and/or pomalidomide), and the anti-CD38 mAb, daratumumab. Refractory is defined as ≤ 25% response to therapy, or progression during therapy or progression within 60 days after completion of therapy. Exclusion Criteria: Active smoldering MM. Active plasma cell leukemia. Documented systemic amyloid light chain amyloidosis. Active CNS MM.

Facility Information:

Facility Name

University of Alabama

City

Birmingham

State/Province

Alabama

ZIP/Postal Code

35294

Country

United States

Facility Name

Mayo Clinic (AZ)

City

Scottsdale

State/Province

Arizona

ZIP/Postal Code

85259

Country

United States

Facility Name

City of Hope

City

Duarte

State/Province

California

ZIP/Postal Code

91010

Country

United States

Facility Name

Jonnsson Comprehensive Cancer Center / University of Los Angeles

City

Los Angeles

State/Province

California

ZIP/Postal Code

90095

Country

United States

Facility Name

Smilow Cancer Hospital

City

New Haven

State/Province

Connecticut

ZIP/Postal Code

06510

Country

United States

Facility Name

University of Florida Health Cancer Center- Shands Cancer Center Hospital

City

Gainesville

State/Province

Florida

ZIP/Postal Code

32608

Country

United States

Facility Name

Sylvester, University of Miami

City

Miami

State/Province

Florida

ZIP/Postal Code

33136

Country

United States

Facility Name

H. Lee Moffitt Cancer Center Research Institute

City

Tampa

State/Province

Florida

ZIP/Postal Code

33612

Country

United States

Facility Name

Emory University / Winship Cancer Institute

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30322

Country

United States

Facility Name

Northside Hospital

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30342

Country

United States

Facility Name

Kaiser Permanente- Hawaii

City

Honolulu

State/Province

Hawaii

ZIP/Postal Code

96819

Country

United States

Facility Name

University of Chicago Medicine

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60637

Country

United States

Facility Name

Indiana University Simon Cancer Center

City

Indianapolis

State/Province

Indiana

ZIP/Postal Code

46202

Country

United States

Facility Name

University of Iowa Hospitals & Clinics

City

Iowa City

State/Province

Iowa

ZIP/Postal Code

52242

Country

United States

Facility Name

Norton Cancer Institute

City

Louisville

State/Province

Kentucky

ZIP/Postal Code

40202

Country

United States

Facility Name

Johns Hopkins Medicine

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21287

Country

United States

Facility Name

Tufts Medical Center

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02111

Country

United States

Facility Name

Massachusetts General Hospital

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114

Country

United States

Facility Name

Dana Farber Cancer Institute

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02215

Country

United States

Facility Name

University of Michigan

City

Ann Arbor

State/Province

Michigan

ZIP/Postal Code

48109

Country

United States

Facility Name

Karmanos Cancer Institute / Wayne State University

City

Detroit

State/Province

Michigan

ZIP/Postal Code

48201

Country

United States

Facility Name

Mayo Clinic Rochester

City

Rochester

State/Province

Minnesota

ZIP/Postal Code

55905

Country

United States

Facility Name

Washington University St. Louis

City

Saint Louis

State/Province

Missouri

ZIP/Postal Code

63110

Country

United States

Facility Name

Hackensack University Medical Center / John Therurer Cancer Center

City

Hackensack

State/Province

New Jersey

ZIP/Postal Code

07601

Country

United States

Facility Name

Valley Hospital

City

Paramus

State/Province

New Jersey

ZIP/Postal Code

07652

Country

United States

Facility Name

Roswell Park Cancer Institute

City

Buffalo

State/Province

New York

ZIP/Postal Code

14203

Country

United States

Facility Name

NYU Perlmutter Cancer Center

City

New York

State/Province

New York

ZIP/Postal Code

10016

Country

United States

Facility Name

Mt Sinai NYC

City

New York

State/Province

New York

ZIP/Postal Code

10029

Country

United States

Facility Name

Columbia University

City

New York

State/Province

New York

ZIP/Postal Code

10032

Country

United States

Facility Name

UNC-Chapel Hill

City

Chapel Hill

State/Province

North Carolina

ZIP/Postal Code

27514

Country

United States

Facility Name

Gabrail Cancer Center

City

Canton

State/Province

Ohio

ZIP/Postal Code

44718

Country

United States

Facility Name

Kaiser Permanente Northwest OR

City

Portland

State/Province

Oregon

Country

United States

Facility Name

Abramson Cancer Center of the University of Pennsylvania

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

Facility Name

Vanderbilt University Ingram Cancer Center

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37232

Country

United States

Facility Name

Baylor Sammons Cancer Center

City

Dallas

State/Province

Texas

ZIP/Postal Code

75246

Country

United States

Facility Name

Swedish Cancer Institute

City

Seattle

State/Province

Washington

ZIP/Postal Code

98109

Country

United States

Facility Name

University Hospital Krems, Department of Internal Medicine II

City

Krems

Country

Austria

Facility Name

Salzburg Regional Hospital Müllner

City

Salzburg

Country

Austria

Facility Name

Medical University Vienna, Department of Internal Medicine I

City

Vienna

Country

Austria

Facility Name

ZNA Stuivenberg

City

Antwerp

Country

Belgium

Facility Name

General Hospital Saint-Jan

City

Brugge

Country

Belgium

Facility Name

Jules Bordet Institute

City

Brussels

ZIP/Postal Code

1000

Country

Belgium

Facility Name

UCL Saint-Luc

City

Brussels

ZIP/Postal Code

B-1200

Country

Belgium

Facility Name

University Hospital Ghent

City

Ghent

Country

Belgium

Facility Name

University Hospital Leuven, Campus Gasthuisberg

City

Leuven

Country

Belgium

Facility Name

UCL Mont-Godinne

City

Yvoir

ZIP/Postal Code

B-5530

Country

Belgium

Facility Name

Claude Huriez Hospital, Department of Blood Diseases

City

Lille

ZIP/Postal Code

59037

Country

France

Facility Name

South Lyon Hospital Center, Department of Clinical Hematology

City

Lyon

ZIP/Postal Code

69002

Country

France

Facility Name

Brabois Adults Hospital

City

Nancy

ZIP/Postal Code

54000

Country

France

Facility Name

Nantes University Hospital Center

City

Nantes

ZIP/Postal Code

44093

Country

France

Facility Name

Hopital Saint-Antoine, Service d´Hematologie Clinique et Therapie Cellulaire

City

Paris

ZIP/Postal Code

75012

Country

France

Facility Name

La Pitie-Salpetriere University Hospital, Department of Clinical Hematology

City

Paris

ZIP/Postal Code

75013

Country

France

Facility Name

Necker Children's Hospital

City

Paris

ZIP/Postal Code

75015

Country

France

Facility Name

BAG Oncology Gemeinschaftspraxis

City

Dresden

ZIP/Postal Code

01307

Country

Germany

Facility Name

University Hospital Freiburg, Department of Internal Medicine I

City

Freiburg

ZIP/Postal Code

D-79106

Country

Germany

Facility Name

Universitätsklinikum Heidelberg Medizinische Klinik V

City

Heidelberg

ZIP/Postal Code

69120

Country

Germany

Facility Name

Universitätsklinikum des Saarlandes Klinik für Innere Medizin I

City

Homburg

ZIP/Postal Code

66421

Country

Germany

Facility Name

Universitätsmedizin Mainz

City

Mainz

ZIP/Postal Code

55122

Country

Germany

Facility Name

University hospital of Tuebingen, Internal Medicine II

City

Tübingen

Country

Germany

Facility Name

Med. Klinik und Poliklinik II Universitätsklinikum

City

Würzburg

Country

Germany

Facility Name

National & Kapodistrain University of Athens School of Medicine, Alexandra Hospital

City

Athens

ZIP/Postal Code

11528

Country

Greece

12. IPD Sharing Statement

Plan to Share IPD

Yes

Citations:

PubMed Identifier

34488662

Citation

Tremblay G, Daniele P, Breeze J, Li L, Shah J, Shacham S, Kauffman M, Engelhardt M, Chari A, Nooka A, Vogl D, Gavriatopoulou M, Dimopoulos MA, Richardson P, Biran N, Siegel D, Vlummens P, Doyen C, Facon T, Mohty M, Meuleman N, Levy M, Costa L, Hoffman JE, Delforge M, Kaminetzky D, Weisel K, Raab M, Dingli D, Tuchman S, Laurent F, Vij R, Schiller G, Moreau P, Richter J, Schreder M, Podar K, Parker T, Cornell RF, Lionel K, Choquet S, Sundar J. Quality of life analyses in patients with multiple myeloma: results from the Selinexor (KPT-330) Treatment of Refractory Myeloma (STORM) phase 2b study. BMC Cancer. 2021 Sep 6;21(1):993. doi: 10.1186/s12885-021-08453-9.

Results Reference

derived

PubMed Identifier

34465265

Citation

Nikolaou A, Ambavane A, Shah A, Ma W, Tosh J, Kapetanakis V, Willson J, Wang F, Hogea C, Gorsh B, Gutierrez B, Sapra S, Suvannasankha A, Samyshkin Y. Belantamab mafodotin for the treatment of relapsed/refractory multiple myeloma in heavily pretreated patients: a US cost-effectiveness analysis. Expert Rev Hematol. 2021 Dec;14(12):1137-1145. doi: 10.1080/17474086.2021.1970522. Epub 2021 Sep 20.

Results Reference

derived

PubMed Identifier

34404623

Citation

Chari A, Florendo E, Mancia IS, Cho H, Madduri D, Parekh S, Richter J, Dhadwal A, Thomas J, Jiang G, Lagana A, Bhalla S, Jagannath S. Optimal Supportive Care With Selinexor Improves Outcomes in Patients With Relapsed/Refractory Multiple Myeloma. Clin Lymphoma Myeloma Leuk. 2021 Dec;21(12):e975-e984. doi: 10.1016/j.clml.2021.07.014. Epub 2021 Jul 18.

Results Reference

derived

PubMed Identifier

31433920

Citation

Chari A, Vogl DT, Gavriatopoulou M, Nooka AK, Yee AJ, Huff CA, Moreau P, Dingli D, Cole C, Lonial S, Dimopoulos M, Stewart AK, Richter J, Vij R, Tuchman S, Raab MS, Weisel KC, Delforge M, Cornell RF, Kaminetzky D, Hoffman JE, Costa LJ, Parker TL, Levy M, Schreder M, Meuleman N, Frenzel L, Mohty M, Choquet S, Schiller G, Comenzo RL, Engelhardt M, Illmer T, Vlummens P, Doyen C, Facon T, Karlin L, Perrot A, Podar K, Kauffman MG, Shacham S, Li L, Tang S, Picklesimer C, Saint-Martin JR, Crochiere M, Chang H, Parekh S, Landesman Y, Shah J, Richardson PG, Jagannath S. Oral Selinexor-Dexamethasone for Triple-Class Refractory Multiple Myeloma. N Engl J Med. 2019 Aug 22;381(8):727-738. doi: 10.1056/NEJMoa1903455.

Results Reference

derived

PubMed Identifier

29381435

Citation

Vogl DT, Dingli D, Cornell RF, Huff CA, Jagannath S, Bhutani D, Zonder J, Baz R, Nooka A, Richter J, Cole C, Vij R, Jakubowiak A, Abonour R, Schiller G, Parker TL, Costa LJ, Kaminetzky D, Hoffman JE, Yee AJ, Chari A, Siegel D, Fonseca R, Van Wier S, Ahmann G, Lopez I, Kauffman M, Shacham S, Saint-Martin JR, Picklesimer CD, Choe-Juliak C, Stewart AK. Selective Inhibition of Nuclear Export With Oral Selinexor for Treatment of Relapsed or Refractory Multiple Myeloma. J Clin Oncol. 2018 Mar 20;36(9):859-866. doi: 10.1200/JCO.2017.75.5207. Epub 2018 Jan 30.

Results Reference

derived

Learn more about this trial

Selinexor Treatment of Refractory Myeloma

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