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A Study 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

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ClinicalTrials.gov Identifier: NCT04414475
Recruitment Status : Recruiting
First Posted : June 4, 2020
Last Update Posted : April 27, 2021
Sponsor:
Information provided by (Responsible Party):
Karyopharm Therapeutics Inc

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Multiple Myeloma, Refractory Drug: Selinexor Drug: Dexamethasone Drug: Bortezomib Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 134 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2b, Open-label, Multi-arm Clinical Trial of Selinexor Plus Low-dose Dexamethasone (Sd) in Patients With Penta-refractory Multiple Myeloma or Selinexor and Bortezomib Plus Low-dose Dexamethasone (SVd) in Patients With Triple-class Refractory Multiple Myeloma
Actual Study Start Date : July 1, 2020
Estimated Primary Completion Date : January 30, 2023
Estimated Study Completion Date : January 30, 2023


Arm Intervention/treatment
Experimental: 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.
Drug: Selinexor
Participants will receive Selinexor oral tablets.
Other Names:
  • KPT-330
  • XPOVIO

Drug: Dexamethasone
Participants will receive Dexamethasone oral tablets.
Other Name: Decadron

Experimental: 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).
Drug: Selinexor
Participants will receive Selinexor oral tablets.
Other Names:
  • KPT-330
  • XPOVIO

Drug: Dexamethasone
Participants will receive Dexamethasone oral tablets.
Other Name: Decadron

Experimental: 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.
Drug: Selinexor
Participants will receive Selinexor oral tablets.
Other Names:
  • KPT-330
  • XPOVIO

Drug: Dexamethasone
Participants will receive Dexamethasone oral tablets.
Other Name: Decadron

Experimental: 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).
Drug: Selinexor
Participants will receive Selinexor oral tablets.
Other Names:
  • KPT-330
  • XPOVIO

Drug: Dexamethasone
Participants will receive Dexamethasone oral tablets.
Other Name: Decadron

Drug: Bortezomib
Participants will receive Bortezomib SC injection.
Other Name: Velcade




Primary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: From the date of randomization up to death (approximately 14 months) ]

Secondary Outcome Measures :
  1. Duration of Response (DOR) [ Time Frame: From the date of randomization to first disease progression or death (approximately 14 months) ]
  2. Clinical Benefit Rate (CBR) [ Time Frame: From the date of randomization up to death (approximately 14 months) ]
  3. Disease control rate (DCR) [ Time Frame: From the date of randomization up to death (approximately 14 months) ]
  4. Progression-Free Survival (PFS) [ Time Frame: From the date of randomization to first disease progression or death (approximately 14 months) ]
  5. Overall Survival (OS) [ Time Frame: From the date of randomization up to death (approximately 14 months) ]
  6. Time to Next Treatment (TTNT) [ Time Frame: From the date of first dose up to death (approximately 14 months) ]
  7. Number of Participants with Adverse Events (AE) [ Time Frame: From start of study drug administration up to follow-up (approximately 3 months) ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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: 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 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.
  • Participants agrees to provide bone marrow aspirate to be used for genetic testing of participants agrees to provide bone marrow aspirate to be used for genetic testing of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA).

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 (mm3)
    2. Platelet count < 75,000/mm3
    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.
  • Receipt of red blood cells (RBC) transfusions within 2 weeks of C1D1.
  • Receipt of platelet transfusion within 1 week of C1D1.
  • Receipt of the following blood growth factors within 2 weeks prior to C1D1: Granulocyte colony stimulating factor, granulocyte-macrophage colony stimulating factor, erythropoietin, or megakaryocyte growth factor.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04414475


Contacts
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Contact: Jatin Shah Chief Medical Officer, MD (617) 658-0600 jshah@karyopharm.com
Contact: Sharon Shacham Chief Scientific Officer, PhD (617) 658-0600 sshacham@karyopharm.com

Locations
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Greece
University General Hospital of Patras Recruiting
Patra, Achaia, Greece, 2654
Contact: Prof. Anargyros Symeonidis    +30 6944960012    argiris.symeonidis@yahoo.gr   
Principal Investigator: Prof. Anargyros Symeonidis         
General Hospital of Athens "ALEXANDRA" Recruiting
Attiki, Athens, Greece, 11528
Contact: Prof. Maria Gavriatopoulou    +30 6934137080    mariagabria@gmail.com   
Principal Investigator: Prof. Maria Gavriatopoulou         
General Hospital of Athens "Evaggelismos" Recruiting
Athens, Attiki, Greece, 10676
Contact: Dr. Sosana Delimpasi    (+30697)7204193    sodeli@yahoo.com   
Principal Investigator: Dr. Sosana Delimpasi         
Theageneion Cancer Hospital Recruiting
Thessaloniki, Greece, 54007
Contact: Eirini Katoudritou    +30 6974872869    eirinikatodritou@gmail.com   
Principal Investigator: Eirini Katoudritou         
Israel
Emek Medical Center Recruiting
Afula, Israel, 1834111
Contact: Evgeni Chubar    972 52 7828012    Chubar_ev@clalit.org.il   
Principal Investigator: Evgeni Chubar         
Assuta Ashdod Medical Center Recruiting
Ashdod, Israel, 7747629
Contact: Merav Leiba    972 58 666 9161    meravlei@assuta.co.il   
Principal Investigator: Merav Leiba         
Barzilai Medical Center Not yet recruiting
Ashkelon, Israel, 7830604
Contact: Anatoly Nemets, MD         
Contact    972 8 6745796    anatolyn@bmc.gov.il   
Principal Investigator: Anatoly Nemets, MD         
Soroka University Medical Center Recruiting
Beer-Sheva, Israel
Contact: Dr. Miri Zekster    050-589-3962    MIRISP2@clalit.org.il   
Principal Investigator: Dr. Miri Zekster         
Bnai-Zion Medical Center Recruiting
Haifa, Israel, 3108
Contact: Tamar Tadmor    972506268114    Tamar.tadmor@b-Zion.org.il   
Principal Investigator: Tamar Tadmor         
Rambam Health Care Campus Recruiting
Haifa, Israel, 3109601
Contact: Noa Lavi    972 50 206 1332    n_lavi@rambam.health.gov.il   
Principal Investigator: Noa Lavi         
Shaare Zedek Medical Center Recruiting
Jerusalem, Israel, 9103102
Contact: Chezi Ganzel    972-53-3342046    ganzelc@szmc.org.il   
Principal Investigator: Chezi Ganzel         
Hadassah Medical Center Recruiting
Jerusalem, Israel, 9112001
Contact: Moshe Gatt    972-505172333    rmoshg@hadassah.org.il   
Principal Investigator: Moshe Gatt         
Meir Medical Center Not yet recruiting
Kfar Saba, Israel, 4428164
Contact: Osnat Jarchowsky, MD       osnat.JARCHOWSKY@clalit.org.il   
Principal Investigator: Osnat Jarchowsky, MD         
Rabin Medical Center (Beilinson Hospital) Recruiting
Petah Tikva, Israel, 49100
Contact: Amos Cohen    972-50-565-1033    amosc@clalit.org.il   
Principal Investigator: Amos Cohen         
The Chaim Sheba Medical Center at Tel HaShomer Recruiting
Ramat Gan, Israel, 52621
Contact: Hila Magen    972 50 406 5432    hila.magen@sheba.health.gov.il   
Principal Investigator: Hila Magen         
Tel Aviv Sourasky Medical Center Recruiting
Tel Aviv, Israel, 64239
Contact: Yael Cohen    972 52 662 2575    yaelcoh@tlvmc.gov.il   
Principal Investigator: Yael Cohen         
Sponsors and Collaborators
Karyopharm Therapeutics Inc
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Responsible Party: Karyopharm Therapeutics Inc
ClinicalTrials.gov Identifier: NCT04414475    
Other Study ID Numbers: XPORT-MM-028
First Posted: June 4, 2020    Key Record Dates
Last Update Posted: April 27, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Karyopharm Therapeutics Inc:
Multiple Myeloma
Selinexor
Penta-refractory Multiple Myeloma
Triple-class Refractory Multiple Myeloma
KPT-330
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone
Bortezomib
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents