Selinexor Treatment of Refractory Myeloma

NCT02336815 | Completed Phase 2 Results DMC

• 1 other identifier: KCP-330-012
• Study Type: interventional
• Target: 202
• Locations: 6 countries
• Sites: 61

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).

Conditions

Multiple Myeloma

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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).

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

Secondary Outcomes (20)

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

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

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

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

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

  Baseline up to a maximum of 13 months

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

  Baseline up to a maximum of 17 months

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

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

Study Arms (2)

Part 1

EXPERIMENTAL

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).

Drug: Selinexor; Drug: Dexamethasone

Part 2

EXPERIMENTAL

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).

Drug: Selinexor; Drug: Dexamethasone

Interventions

Selinexor DRUG

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

Also known as: KPT-330

Part 1; Part 2

Dexamethasone DRUG

20 mg was given with each dose of Selinexor.

Part 1; Part 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Karyopharm Therapeutics Inc: lead

Study Sites (61)

University of Alabama

Birmingham, Alabama, 35294, United States

Location

Mayo Clinic (AZ)

Scottsdale, Arizona, 85259, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

Jonnsson Comprehensive Cancer Center / University of Los Angeles

Los Angeles, California, 90095, United States

Location

Smilow Cancer Hospital

New Haven, Connecticut, 06510, United States

Location

University of Florida Health Cancer Center- Shands Cancer Center Hospital

Gainesville, Florida, 32608, United States

Location

Sylvester, University of Miami

Miami, Florida, 33136, United States

Location

H. Lee Moffitt Cancer Center Research Institute

Tampa, Florida, 33612, United States

Location

Emory University / Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Northside Hospital

Atlanta, Georgia, 30342, United States

Location

Kaiser Permanente- Hawaii

Honolulu, Hawaii, 96819, United States

Location

University of Chicago Medicine

Chicago, Illinois, 60637, United States

Location

Indiana University Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

University of Iowa Hospitals & Clinics

Iowa City, Iowa, 52242, United States

Location

Norton Cancer Institute

Louisville, Kentucky, 40202, United States

Location

Johns Hopkins Medicine

Baltimore, Maryland, 21287, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Karmanos Cancer Institute / Wayne State University

Detroit, Michigan, 48201, United States

Location

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

Location

Washington University St. Louis

St Louis, Missouri, 63110, United States

Location

Hackensack University Medical Center / John Therurer Cancer Center

Hackensack, New Jersey, 07601, United States

Location

Valley Hospital

Paramus, New Jersey, 07652, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14203, United States

Location

NYU Perlmutter Cancer Center

New York, New York, 10016, United States

Location

Mt Sinai NYC

New York, New York, 10029, United States

Location

Columbia University

New York, New York, 10032, United States

Location

UNC-Chapel Hill

Chapel Hill, North Carolina, 27514, United States

Location

Gabrail Cancer Center

Canton, Ohio, 44718, United States

Location

Kaiser Permanente Northwest OR

Portland, Oregon, United States

Location

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Vanderbilt University Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

Baylor Sammons Cancer Center

Dallas, Texas, 75246, United States

Location

Swedish Cancer Institute

Seattle, Washington, 98109, United States

Location

University Hospital Krems, Department of Internal Medicine II

Krems, Austria

Location

Salzburg Regional Hospital Müllner

Salzburg, Austria

Location

Medical University Vienna, Department of Internal Medicine I

Vienna, Austria

Location

ZNA Stuivenberg

Antwerp, Belgium

Location

General Hospital Saint-Jan

Bruges, Belgium

Location

Jules Bordet Institute

Brussels, 1000, Belgium

Location

UCL Saint-Luc

Brussels, B-1200, Belgium

Location

University Hospital Ghent

Ghent, Belgium

Location

University Hospital Leuven, Campus Gasthuisberg

Leuven, Belgium

Location

UCL Mont-Godinne

Yvoir, B-5530, Belgium

Location

Claude Huriez Hospital, Department of Blood Diseases

Lille, 59037, France

Location

South Lyon Hospital Center, Department of Clinical Hematology

Lyon, 69002, France

Location

Brabois Adults Hospital

Nancy, 54000, France

Location

Nantes University Hospital Center

Nantes, 44093, France

Location

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

Paris, 75012, France

Location

La Pitie-Salpetriere University Hospital, Department of Clinical Hematology

Paris, 75013, France

Location

Necker Children's Hospital

Paris, 75015, France

Location

BAG Oncology Gemeinschaftspraxis

Dresden, 01307, Germany

Location

University Hospital Freiburg, Department of Internal Medicine I

Freiburg im Breisgau, D-79106, Germany

Location

Universitätsklinikum Heidelberg Medizinische Klinik V

Heidelberg, 69120, Germany

Location

Universitätsklinikum des Saarlandes Klinik für Innere Medizin I

Homburg, 66421, Germany

Location

Universitätsmedizin Mainz

Mainz, 55122, Germany

Location

University hospital of Tuebingen, Internal Medicine II

Tübingen, Germany

Location

Med. Klinik und Poliklinik II Universitätsklinikum

Würzburg, Germany

Location

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

Athens, 11528, Greece

Location

Related Publications (5)

• 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.

  PMID: 34488662 DERIVED

• 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.

  PMID: 34465265 DERIVED

• 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.

  PMID: 34404623 DERIVED

• 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.

  PMID: 31433920 DERIVED

• 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.

  PMID: 29381435 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

selinexor; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Results Point of Contact

• Title: Jatin Shah, MD
• Organization: Karyopharm Therapeutics Inc.

jshah@karyopharm.com

(617) 658-0600

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2015
• First Posted: January 13, 2015
• Study Start: May 26, 2015
• Primary Completion: July 26, 2019
• Study Completion: July 26, 2019
• Last Updated: January 26, 2023
• Results First Posted: August 13, 2020

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will share

Locations

AU (3); GR (1); BE (7); US (36); FR (7); DE (7)