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Selinexor With Alternating Bortezomib or Lenalidomide Plus Dexamethasone in TIE Newly Diagnosed MM Patients (SABLe)

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ClinicalTrials.gov Identifier: NCT04717700
Recruitment Status : Not yet recruiting
First Posted : January 22, 2021
Last Update Posted : January 22, 2021
Sponsor:
Collaborators:
Karyopharm Therapeutics Inc
Odense Patient Data Explorative Network
Information provided by (Responsible Party):
Ida Bruun Kristensen, Odense University Hospital

Brief Summary:
An open-label randomized (1:1) phase 2 study between a standard arm of VRD light versus an experimental arm of selinexor in combination with lenalidomide/ bortezomib and dexamethasone to newly diagnosed, transplant in-eligible symptomatic multiple myeloma patients in a multicenter international set-up within the Nordic Multiple Myeloma Study Group

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Selinexor 20 MG Oral Tablet Drug: Bortezomib Injection Drug: Lenalidomide capsule Drug: Dexamethasone Oral Phase 2

Detailed Description:

An open-label randomized (1:1) phase 2 study between a standard arm of VRD light versus an experimental arm of selinexor in combination with lenalidomide/ bortezomib and dexamethasone to newly diagnosed transplant in-eligible symptomatic multiple myeloma patients in a multicenter international set-up with in the Nordic Multiple Myeloma Study Group.

Each arm will include 50 patients with a total number of participants of 100 patients, recruited within the NMSG collaborating countries. After induction patient will be treated with continued lenalidomide-dexamethasone according to SWOG, with continuous 40mg selinexor weekly in the selinexor arm (experimental arm B).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Selinexor With Alternating Bortezomib or Lenalidomide Plus Dexamethasone in Transplant Ineligible Newly Diagnosed Multiple Myeloma Patients (SABLe): An Investigator Sponsored Trial
Estimated Study Start Date : April 1, 2021
Estimated Primary Completion Date : June 1, 2024
Estimated Study Completion Date : June 1, 2029


Arm Intervention/treatment
Active Comparator: A VRD-light
Bortezomib sc 1.3mg/sqm once weekly Lenalidomide oral 25mg d 1-21 Dexamethasone 20mg d 1+2, 8+9 and 15+16 in 28 days cycles for up to 16 cycles followed by continuos lenalidomide-dexamethasone
Drug: Bortezomib Injection
Comparing an alternating regimen of selinexor-lenalidomide/bortezomib-dexamethasone to standard bortezomib-lenalidomide-dexamethasone
Other Name: Velcade

Drug: Lenalidomide capsule
Comparing an alternating regimen of selinexor-lenalidomide/bortezomib-dexamethasone to standard bortezomib-lenalidomide-dexamethasone
Other Name: Revlimid

Drug: Dexamethasone Oral
Comparing an alternating regimen of selinexor-lenalidomide/bortezomib-dexamethasone to standard bortezomib-lenalidomide-dexamethasone
Other Name: Neofordex

Experimental: B -selinexor-lenalidomide/bortezomib-dexamethasone

Alternating cycles of:

Selinexor oral 40mg once weekly Lenalidomide oral 25mg d 1-21 Dexamethasone 20mg d 1+2, 8+9 and 15+16 i 28 days cycles and Selinexor oral 80mg once weekly Bortezomib sc 1.3mg/sqm once weekly Dexamethasone 20mg d 1+2, 8+9 and 15+16 in 28 days cycles for up to 16 cycles (8 of each, alternating) followed by continuos selinexor 40mg(once weekly)-lenalidomide-dexamethasone

for up to 16 cycles followed by continuos lenalidomide-dexamethasone

Drug: Selinexor 20 MG Oral Tablet
Comparing an alternating regimen of selinexor-lenalidomide/bortezomib-dexamethasone to standard bortezomib-lenalidomide-dexamethasone
Other Name: Xpovio

Drug: Bortezomib Injection
Comparing an alternating regimen of selinexor-lenalidomide/bortezomib-dexamethasone to standard bortezomib-lenalidomide-dexamethasone
Other Name: Velcade

Drug: Lenalidomide capsule
Comparing an alternating regimen of selinexor-lenalidomide/bortezomib-dexamethasone to standard bortezomib-lenalidomide-dexamethasone
Other Name: Revlimid

Drug: Dexamethasone Oral
Comparing an alternating regimen of selinexor-lenalidomide/bortezomib-dexamethasone to standard bortezomib-lenalidomide-dexamethasone
Other Name: Neofordex




Primary Outcome Measures :
  1. Increased ORR in arm B (defined as ≥PR) at end of induction, defined according to IMWG response criteria [ Time Frame: Estimated at 4-8 weeks after end of induction ]
    ORR at end of induction, with response defined according to IMWG response criteria


Secondary Outcome Measures :
  1. Increased VGPR rate at end of induction in arm B [ Time Frame: Estimated at 4-8 weeks after end of induction ]
    VGPR rate at end of induction

  2. Increased rate of MRD negativity at end of induction in arm B [ Time Frame: Estimated at 4-8 weeks after end of induction ]
    MRD negativity by NGS at end of induction

  3. Decreased time to response in arm B [ Time Frame: Estimated monthly during the first 64 weeks ]
    Time to at least PR from start of treatment

  4. Evaluate toxicity rates between arm A and B, including rates of secondary primary malignancies [ Time Frame: Estimated at 4-8 weeks after end of induction ]
    Comparison of toxicity rates according to NCI-CTCAE v4.03

  5. Decreased time to at least VGPR [ Time Frame: Estimated monthly during the first 64 weeks ]
    Time to at least VGPR from start of treatment



Information from the National Library of Medicine

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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:

Inclusion Criteria:

Patients must meet all of the following inclusion criteria to be eligible to enroll in this study:

  1. Age > 18 years
  2. Willing and able to provide written informed consent in accordance with national, local, and institutional guidelines. The patient must provide informed consent prior to the first screening procedure
  3. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of ≤ 2. ECOG 3 allowed if caused by myeloma
  4. Newly diagnosed multiple myeloma with treatment demanding disease as defined by IMWG (Rajkumar, Dimopoulos et al. 2014) and measurable disease as defined IMWG 2016 criteria (Table 5) (Kumar, Paiva et al. 2016)
  5. By treating physician considered in-eligible for high-dose therapy with stem-cell transplant
  6. Patients must have received no prior chemotherapy for multiple myeloma. Patients must have received no prior radiotherapy to a large area of the pelvis (more than half of the pelvis). Patients must have received no prior steroid treatment for myeloma with the exception of a maximum of 14 days of treatment for symptom control (including dexamethasone 40mg).
  7. Adequate hepatic function within 7 days prior to C1D1:

    1. Total bilirubin < 1.5 × upper limit of normal (ULN) (except patients with Gilbert's syndrome who must have a total bilirubin of < 3 × ULN), and
    2. Alanine aminotransferase (ALT) normal to <2 × ULN.
  8. Adequate renal function within 7 days prior to C1D1 as determined by estimated GFR of ≥ 30 mL/min, calculated using standard formula.

    1. Adequate hematopoietic function within 7 days prior to C1D1: Absolute neutrophil count ≥1000/mm3, and platelet count ≥100,000/mm3 (patients for whom <50% of bone marrow nucleated cells are plasma cells). If cytopenias are due a plasma cell infiltration in the bone marrow (biopsy-proven heavy-marrow involvement, as defined by having at least 30% marrow cellularity, with > 50% of the cells being malignant plasma cells (documented marrow results required)); in this case, although there are no required lower limits of normal for the blood counts, the treating physician must use his/her medical judgment as to the appropriateness of this study therapy for these patients.
    2. Erythropoietin-analogues are allowed.
    3. Patients must have:

      • At least a 1-week interval from the last platelet transfusion prior to the screening platelet assessment.

    However, patients may receive RBC and/or platelet transfusions as clinically indicated per institutional guidelines during the study.

  9. Female patients of childbearing potential must have a negative serum pregnancy test at Screening. Female patients of childbearing potential and fertile male patients who are sexually active with a female of childbearing potential must use highly effective methods of contraception throughout the study and for 3 months following the last dose of study treatment.
  10. Patients must be able to take prophylactic anticoagulation as recommended by study
  11. Patients with pathologic fractures, infection at diagnosis or symptomatic hyperviscosity must have these conditions attended to prior to registration (i.e., intramedullary rod, I.V. antibiotics, plasmapheresis)

Exclusion Criteria:

Exclusion Criteria:

Patients meeting any of the following exclusion criteria are not eligible to enroll in this study:

  1. Has received selinexor or another XPO1 inhibitor previously.
  2. Has any concurrent medical condition or disease (eg, uncontrolled active hypertension, uncontrolled active diabetes, active systemic infection, etc.) that is likely to interfere with study procedures.
  3. Known intolerance, hypersensitivity, or contraindication to glucocorticoids, bortezomib, lenalidomide and selinexor.
  4. Pregnant or breastfeeding females.
  5. Life expectancy of less than 6 months.
  6. Active, unstable cardiovascular function, as indicated by the presence of:

    1. Symptomatic ischemia, or
    2. Uncontrolled clinically significant conduction abnormalities (eg, patients with ventricular tachycardia on anti-arrhythmics are excluded; patients with first degree atrioventricular block or asymptomatic left anterior fascicular block/right bundle branch block will not be excluded), or
    3. Congestive heart failure of New York Heart Association Class ≥3 or known left ventricular ejection fraction <40%, or
    4. Myocardial infarction within 6 months prior to C1D1.
  7. Any active gastrointestinal dysfunction interfering with the patient's ability to swallow tablets, or any active gastrointestinal dysfunction that could interfere with absorption of study treatment.
  8. Inability or unwillingness to take supportive medications such as anti-nausea and anti-anorexia agents as recommended by the National Comprehensive Cancer Network® (NCCN) Clinical Practice Guidelines in Oncology (CPGO) (NCCN CPGO) for antiemesis and anorexia/cachexia (palliative care).
  9. Any active, serious psychiatric, medical, or other conditions/situations that, in the opinion of the Investigator, could interfere with treatment, compliance, or the ability to give informed consent.
  10. Contraindication to any of the required concomitant drugs or supportive treatments.
  11. Patients unwilling or unable to comply with the protocol

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): NCT04717700


Contacts
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Contact: Ida B Kristensen, MD +4565411152 ida.bruun.kristensen@rsyd.dk

Locations
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Denmark
Aalborg University Hospital
Aalborg, Denmark
Contact: Henrik Gregersen, MD         
Sydvestjysk Sygehus Esbjerg
Esbjerg, Denmark
Contact: Per T Pedersen, MD         
Herlev Hospital
Herlev, Denmark
Contact: Carsten Helleberg         
Regionshospitalet Holstebro
Holstebro, Denmark
Contact: Robert S Pedersen         
Odense University Hospital
Odense, Denmark
Contact: Ida B Kristensen       ida.bruun.kristensen@rsyd.dk   
Norway
Oslo Universitets Hospital
Oslo, Norway
Contact: Hanne Norseth         
St. Olavs University Hospital
Trondheim, Norway
Contact: Tobias S Sloerdahl         
Sponsors and Collaborators
Ida Bruun Kristensen
Karyopharm Therapeutics Inc
Odense Patient Data Explorative Network
Investigators
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Principal Investigator: Ida B Kristensen, MB Odense University Hospital
Principal Investigator: Hanne Norseth, MD Oslo University Hospital
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Responsible Party: Ida Bruun Kristensen, MD, Odense University Hospital
ClinicalTrials.gov Identifier: NCT04717700    
Other Study ID Numbers: NMSG 29/21
First Posted: January 22, 2021    Key Record Dates
Last Update Posted: January 22, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Ida Bruun Kristensen, Odense University Hospital:
selinexor
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
Lenalidomide
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
Immunologic Factors
Angiogenesis Inhibitors