A Study of Selinexor (Seli) + Low-dose Dexamethasone (LDD) in Penta-refractory Multiple Myeloma (MM), Seli and Bortezomib + LDD in Triple-class Refractory MM.

NCT ID: NCT04414475

Last Updated: 2026-02-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

127 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-07-01

Study Completion Date

2028-01-31

Brief Summary

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The purpose of this study is to assess the efficacy, antitumor activity, safety and tolerability of selinexor plus low-dose dexamethasone in participants with penta-refractory multiple myeloma or selinexor and bortezomib plus low-dose dexamethasone in participants with triple-class refractory multiple myeloma.

Detailed Description

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Conditions

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Multiple Myeloma, Refractory

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Selinexor + Low-dose Dexamethasone (Sd-40 BIW)

Participants will receive fixed dose of 40 milligram (mg) of Selinexor oral tablet followed by 20 mg of low-dose Dexamethasone oral tablet twice weekly (BIW) on Days 1, 3, 8, 10, 15, 17, 22, and 24 of each 28-day cycle.

Group Type EXPERIMENTAL

Selinexor

Intervention Type DRUG

Participants will receive Selinexor oral tablets.

Dexamethasone

Intervention Type DRUG

Participants will receive Dexamethasone oral tablets.

Selinexor + Low-dose Dexamethasone (Sd-100 QW)

Participants will receive fixed dose of 100 mg of Selinexor oral tablet followed by 40 mg of low-dose Dexamethasone oral tablet once weekly (QW) on Days 1, 8, 15, and 22 of each 28-day cycle. (Dexamethasone may be given as 20 mg on days 1 and 2 of each week at the discretion of the treating physician).

Group Type EXPERIMENTAL

Selinexor

Intervention Type DRUG

Participants will receive Selinexor oral tablets.

Dexamethasone

Intervention Type DRUG

Participants will receive Dexamethasone oral tablets.

Selinexor + Low-dose Dexamethasone (Sd-80 BIW)

Participants will receive fixed dose of 80 mg of Selinexor oral tablet followed by 20 mg of low-dose Dexamethasone oral tablet BIW on Days 1, 3, 8, 10,15, 17, 22, and 24 of each 28-day cycle. Closed for recruitment.

Group Type EXPERIMENTAL

Selinexor

Intervention Type DRUG

Participants will receive Selinexor oral tablets.

Dexamethasone

Intervention Type DRUG

Participants will receive Dexamethasone oral tablets.

Selinexor + Bortezomib + Dexamethasone (SVd)

Participants will receive fixed dose of 100 mg of Selinexor oral tablet on Days 1, 8, 15, 22, and 29 followed by 1.3 milligram per square-meter (mg/m\^2) of Bortezomib subcutaneous (SC) injection on Days 1, 8, 15, and 22 and followed by 40 mg of low-dose Dexamethasone oral tablet on Days 1, 8, 15, 22, and 29 of each 35-day cycle (Dexamethasone dose may be split to 20 mg on days 1 and 2 of each week at the discretion of the treating physician). Closed for recruitment.

Group Type EXPERIMENTAL

Selinexor

Intervention Type DRUG

Participants will receive Selinexor oral tablets.

Dexamethasone

Intervention Type DRUG

Participants will receive Dexamethasone oral tablets.

Bortezomib

Intervention Type DRUG

Participants will receive Bortezomib SC injection.

Interventions

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Selinexor

Participants will receive Selinexor oral tablets.

Intervention Type DRUG

Dexamethasone

Participants will receive Dexamethasone oral tablets.

Intervention Type DRUG

Bortezomib

Participants will receive Bortezomib SC injection.

Intervention Type DRUG

Other Intervention Names

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KPT-330 XPOVIO Decadron Velcade

Eligibility Criteria

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Inclusion Criteria

* Age greater than or equal to (\>=)18 years at the time of signing informed consent.
* Written informed consent in accordance with federal, local, and institutional guidelines.
* Measurable MM based on IMWG guidelines as defined by at least one of the following:

1. Serum M-protein \>= 0.5 gram per deciliter (g/dL) by serum protein electrophoresis (SPEP) or, for Immunoglobulin (Ig) A myeloma, by quantitative IgA.
2. Urinary M-protein excretion \>= 200 mg/24 hours.
3. Free light chain (FLC) \>= 100 milligram per liter (mg/L), provided that the FLC ratio is abnormal.
* Only for arms Sd-40 BIW, Sd-100 QW and Sd-80 BIW prior to protocol version (PV) 5.0: Participants must have relapsed or refractory multiple myeloma (RRMM) and have previously received at least 4 anti-MM prior therapies and have MM that is refractory to previous treatment with at least 2 proteasome inhibitors (PIs), at least 2 immunomodulatory agent (IMiDs), and 1 anti-cluster of differentiation (CD38) monoclonal antibody. Refractory is defined as lesser than or equal to (\<=) 25 percent (%) response to therapy, or progression during therapy or progression within 60 days after completion of therapy.
* Only for Arms Sd-40 BIW and Sd-100 QW as of PV 5.0: Participants must have RR MM and have been previously treated with \>=3 anti-MM therapies (with exposure to at least 2 PI drugs, at least 2 IMiDs, and 1 anti-CD38 monoclonal antibody), and be refractory to at least 1 drug of each class (PI/IMiD/anti-CD38). Refractory is defined as \<=25% response to therapy or progression during therapy or progression within 60 days after completion of therapy.
* Only for arm SVd: Participants must have previously received 1 to 5 anti-MM prior therapies and have MM that is refractory to previous treatment with at least 1 PI, at least 1 IMiD, and 1 anti- CD38 monoclonal antibody.
* Eastern Cooperative Oncology Group (ECOG) performance status of \<= 2.
* Female participants of childbearing potential must agree to use dual methods of contraception and have a negative serum pregnancy test at screening, and male participants must use an effective barrier method of contraception if sexually active with a female of childbearing potential. For both male and female participants, effective methods of contraception must be used throughout the study and for 7 months for female and 4 months for male following the discontinuation of study treatment.

Exclusion Criteria

* Active plasma cell leukemia.
* Documented systemic amyloid light chain amyloidosis.
* Active central nervous system MM.
* Only for SVd arm: Greater than Grade 2 peripheral neuropathy or Grade \>= 2 peripheral neuropathy with pain at baseline, regardless of whether or not the participant is currently receiving medication.
* Radiation, chemotherapy, immunotherapy, or any other anticancer therapy (including investigational therapies) \<= 2 weeks prior to Cycle 1 Day 1 (C1D1). (Steroids are permitted up to 1 pulse of 40 mg per day for 4 days in the 2 weeks prior to C1D1).
* Active graft vs. host disease (after allogeneic stem cell transplantation) at C1D1.
* Ongoing clinically significant non-hematological toxicities from prior treatments that are Grade greater than (\>) 2 at C1D1.
* Inadequate hepatic function defined as total bilirubin \>= 2x upper limit of normal (ULN) (\>= 3x ULN for participants with Gilbert's syndrome), aspartate transaminase (AST) \>= 2.5x ULN, and alanine transaminase (ALT) \>= 2.5x ULN.
* Inadequate renal function defined as estimated creatinine clearance of lesser than (\<) 20 milliliter per minute (mL/min), calculated using the formula of Cockroft and Gault.
* Inadequate hematopoietic function defined as the following:

1. Absolute neutrophil count (ANC) \< 1000/cubic millimeter (mm\^3)
2. Platelet count \< 75,000/mm\^3
3. Hemoglobin (Hb) level \< 8.5 g/dL
* Life expectancy of \< 4 months, based on the opinion of the Investigator.
* Major surgery within 4 weeks prior to C1D1.
* Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within 1 week prior to first dose.
* Active gastrointestinal dysfunction interfering with the ability to swallow tablets, or any gastrointestinal dysfunction that could interfere with absorption of the study treatment.
* Known active hepatitis A, B, or C infection; or known to be positive for hepatitis C virus RNA or hepatitis B virus surface antigen.
* Female participants who are pregnant or lactating.
* Known intolerance, hypersensitivity, or contraindication to glucocorticoid therapy at C1D1.
* Concurrent therapy with approved or investigational anticancer therapeutic including topical therapies.
* Prior exposure to a SINE compound, including selinexor.
* Serious, active psychiatric or active medical conditions which, in the opinion of the Investigator or the Sponsor, could interfere with the participation in the study.
* Contraindication to any of the required concomitant drugs or supportive treatments.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Karyopharm Therapeutics Inc

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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University General Hospital of Patras

Pátrai, Achaia, Greece

Site Status COMPLETED

General Hospital of Athens "Alexandra"

Attiki, Athens, Greece

Site Status RECRUITING

General Hospital of Athens "Evangelismos"

Athens, Attica, Greece

Site Status RECRUITING

Theageneion Cancer Hospital

Thessaloniki, Thessaloniki, Greece

Site Status RECRUITING

Emek Medical Center

Afula, Afula, Israel

Site Status RECRUITING

Assuta Ashdod Medical Center

Ashdod, Ashdod, Israel

Site Status RECRUITING

Bnai-Zion Medical Center

Haifa, Haifa District, Israel

Site Status RECRUITING

Rambam Health Care Campus

Haifa, Haifa District, Israel

Site Status RECRUITING

Shaare Zedek Medical Center

Jerusalem, Jerusalem, Israel

Site Status RECRUITING

Hadassah Medical Center

Jerusalem, Jerusalem, Israel

Site Status RECRUITING

Rabin Medical Center (Beilinson Hospital)

Petah Tikva, Petah Tikva, Israel

Site Status RECRUITING

The Chaim Sheba Medical Center at Tel HaShomer

Ramat Gan, Ramat Gan, Israel

Site Status RECRUITING

Tel Aviv Sourasky Medical Center

Tel Aviv, Tel Aviv, Israel

Site Status RECRUITING

Barzilai Medical Center

Ashkelon, , Israel

Site Status RECRUITING

Soroka University Medical Center

Beersheba, , Israel

Site Status ACTIVE_NOT_RECRUITING

Meir Medical Center

Kfar Saba, , Israel

Site Status COMPLETED

Countries

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Greece Israel

Central Contacts

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Karyopharm Medical Information

Role: CONTACT

(888) 209-9326

Facility Contacts

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Prof. Maria Gavriatopoulou

Role: primary

+30 693 413 7080

Dr. Sosana Delimpasi

Role: primary

+30 697 720 4193

Eirini Katoudritou

Role: primary

+30 697 487 2869

Evgeni Chubar

Role: primary

972 52 7828012

Merav Leiba

Role: primary

972 58 666 9161

Tamar Tadmor

Role: primary

972506268114

Noa Lavi

Role: primary

972 50 206 1332

Chezi Ganzel

Role: primary

972-53-3342046

Moshe Gatt

Role: primary

972-505172333

Amos Cohen

Role: primary

972-50-565-1033

Hila Magen

Role: primary

972 50 406 5432

Yael Cohen

Role: primary

972 52 662 2575

Anatoly Nemets, MD

Role: primary

Role: backup

972 8 6745796

References

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White D, Schiller GJ, Madan S, Lentzsch S, Chubar E, Lavi N, Van Domelen DR, Bentur OS, Baljevic M. Efficacy and safety of once weekly selinexor 40 mg versus 60 mg with pomalidomide and dexamethasone in relapsed and/or refractory multiple myeloma. Front Oncol. 2024 May 17;14:1352281. doi: 10.3389/fonc.2024.1352281. eCollection 2024.

Reference Type DERIVED
PMID: 38826786 (View on PubMed)

Other Identifiers

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XPORT-MM-028

Identifier Type: -

Identifier Source: org_study_id

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