Selinexor Treatment of Refractory Myeloma

NCT ID: NCT02336815

Last Updated: 2023-01-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 202 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-05-26
• Study Completion Date: 2019-07-26

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.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1

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).

Group Type: EXPERIMENTAL

Selinexor

Intervention Type: DRUG

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

Dexamethasone

Intervention Type: DRUG

20 mg was given with each dose of Selinexor.

Part 2

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).

Group Type: EXPERIMENTAL

Selinexor

Intervention Type: DRUG

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

Dexamethasone

Intervention Type: DRUG

20 mg was given with each dose of Selinexor.

Interventions

Selinexor

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

Intervention Type: DRUG

Dexamethasone

20 mg was given with each dose of Selinexor.

Intervention Type: DRUG

Other Intervention Names

KPT-330

Eligibility Criteria

Inclusion Criteria

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

1. Serum M-protein ≥ 0.5 g/dL by serum electrophoresis (SPEP) or for IgA myeloma, by quantitative IgA

2. Urinary M-protein excretion ≥ 200 mg/24 hours

3. Free Light Chain (FLC) ≥ 100 mg/L, provided that the FLC ratio is abnormal

4. If serum protein electrophoresis is felt to be unreliable for routine M-protein measurement, then quantitative Ig levels by nephelometry or turbidimetry are acceptable

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Karyopharm Therapeutics Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of Alabama

Birmingham, Alabama, United States

Mayo Clinic (AZ)

Scottsdale, Arizona, United States

City of Hope

Duarte, California, United States

Jonnsson Comprehensive Cancer Center / University of Los Angeles

Los Angeles, California, United States

Smilow Cancer Hospital

New Haven, Connecticut, United States

University of Florida Health Cancer Center- Shands Cancer Center Hospital

Gainesville, Florida, United States

Sylvester, University of Miami

Miami, Florida, United States

H. Lee Moffitt Cancer Center Research Institute

Tampa, Florida, United States

Emory University / Winship Cancer Institute

Atlanta, Georgia, United States

Northside Hospital

Atlanta, Georgia, United States

Kaiser Permanente- Hawaii

Honolulu, Hawaii, United States

University of Chicago Medicine

Chicago, Illinois, United States

Indiana University Simon Cancer Center

Indianapolis, Indiana, United States

University of Iowa Hospitals & Clinics

Iowa City, Iowa, United States

Norton Cancer Institute

Louisville, Kentucky, United States

Johns Hopkins Medicine

Baltimore, Maryland, United States

Tufts Medical Center

Boston, Massachusetts, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

University of Michigan

Ann Arbor, Michigan, United States

Karmanos Cancer Institute / Wayne State University

Detroit, Michigan, United States

Mayo Clinic Rochester

Rochester, Minnesota, United States

Washington University St. Louis

St Louis, Missouri, United States

Hackensack University Medical Center / John Therurer Cancer Center

Hackensack, New Jersey, United States

Valley Hospital

Paramus, New Jersey, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

NYU Perlmutter Cancer Center

New York, New York, United States

Mt Sinai NYC

New York, New York, United States

Columbia University

New York, New York, United States

UNC-Chapel Hill

Chapel Hill, North Carolina, United States

Gabrail Cancer Center

Canton, Ohio, United States

Kaiser Permanente Northwest OR

Portland, Oregon, United States

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Vanderbilt University Ingram Cancer Center

Nashville, Tennessee, United States

Baylor Sammons Cancer Center

Dallas, Texas, United States

Swedish Cancer Institute

Seattle, Washington, United States

University Hospital Krems, Department of Internal Medicine II

Krems, , Austria

Salzburg Regional Hospital Müllner

Salzburg, , Austria

Medical University Vienna, Department of Internal Medicine I

Vienna, , Austria

ZNA Stuivenberg

Antwerp, , Belgium

General Hospital Saint-Jan

Bruges, , Belgium

Jules Bordet Institute

Brussels, , Belgium

UCL Saint-Luc

Brussels, , Belgium

University Hospital Ghent

Ghent, , Belgium

University Hospital Leuven, Campus Gasthuisberg

Leuven, , Belgium

UCL Mont-Godinne

Yvoir, , Belgium

Claude Huriez Hospital, Department of Blood Diseases

Lille, , France

South Lyon Hospital Center, Department of Clinical Hematology

Lyon, , France

Brabois Adults Hospital

Nancy, , France

Nantes University Hospital Center

Nantes, , France

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

Paris, , France

La Pitie-Salpetriere University Hospital, Department of Clinical Hematology

Paris, , France

Necker Children's Hospital

Paris, , France

BAG Oncology Gemeinschaftspraxis

Dresden, , Germany

University Hospital Freiburg, Department of Internal Medicine I

Freiburg im Breisgau, , Germany

Universitätsklinikum Heidelberg Medizinische Klinik V

Heidelberg, , Germany

Universitätsklinikum des Saarlandes Klinik für Innere Medizin I

Homburg, , Germany

Universitätsmedizin Mainz

Mainz, , Germany

University hospital of Tuebingen, Internal Medicine II

Tübingen, , Germany

Med. Klinik und Poliklinik II Universitätsklinikum

Würzburg, , Germany

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

Athens, , Greece

Countries

United States; Austria; Belgium; France; Germany; Greece

References

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.

Reference Type: DERIVED

PMID: 34488662 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34465265 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34404623 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31433920 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 29381435 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

KCP-330-012

Identifier Type: -

Identifier Source: org_study_id