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

NCT04717700 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: NMSG 29/21
• Study Type: interventional
• Target: 50
• Locations: 3 countries
• Sites: 11

Brief Summary

An unrandomized phase 2 study 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

Conditions

Multiple Myeloma

Keywords

selinexor

Outcome Measures

Primary Outcomes (1)

• Increased ORR in arm B (defined as ≥PR) at end of induction, defined according to IMWG response criteria

  ORR at end of induction, with response defined according to IMWG response criteria

  Estimated at 4-8 weeks after end of induction

Secondary Outcomes (5)

• Increased VGPR rate at end of induction in arm B

  Estimated at 4-8 weeks after end of induction

• Increased rate of MRD negativity at end of induction in arm B

  Estimated at 4-8 weeks after end of induction

• Decreased time to response in arm B

  Estimated monthly during the first 64 weeks

• Evaluate toxicity rates between arm A and B, including rates of secondary primary malignancies

  Estimated at 4-8 weeks after end of induction

• Decreased time to at least VGPR

  Estimated monthly during the first 64 weeks

Study Arms (1)

B -selinexor-lenalidomide/bortezomib-dexamethasone

EXPERIMENTAL

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; Drug: Bortezomib Injection; Drug: Lenalidomide capsule; Drug: Dexamethasone Oral

Interventions

Selinexor 20 MG Oral Tablet DRUG

Comparing an alternating regimen of selinexor-lenalidomide/bortezomib-dexamethasone to standard bortezomib-lenalidomide-dexamethasone

Also known as: Xpovio

B -selinexor-lenalidomide/bortezomib-dexamethasone

Bortezomib Injection DRUG

Comparing an alternating regimen of selinexor-lenalidomide/bortezomib-dexamethasone to standard bortezomib-lenalidomide-dexamethasone

Also known as: Velcade

B -selinexor-lenalidomide/bortezomib-dexamethasone

Lenalidomide capsule DRUG

Comparing an alternating regimen of selinexor-lenalidomide/bortezomib-dexamethasone to standard bortezomib-lenalidomide-dexamethasone

Also known as: Revlimid

B -selinexor-lenalidomide/bortezomib-dexamethasone

Dexamethasone Oral DRUG

Comparing an alternating regimen of selinexor-lenalidomide/bortezomib-dexamethasone to standard bortezomib-lenalidomide-dexamethasone

Also known as: Neofordex

B -selinexor-lenalidomide/bortezomib-dexamethasone

Eligibility Criteria

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

You may qualify if:

• Age \> 18 years
• 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
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of ≤ 2. ECOG 3 allowed if caused by myeloma
• 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)
• By treating physician considered in-eligible for high-dose therapy with stem-cell transplant
• 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).
• Adequate hepatic function within 7 days prior to C1D1:
• 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
• Alanine aminotransferase (ALT) normal to \<2 × ULN.
• Adequate renal function within 7 days prior to C1D1 as determined by estimated GFR of ≥ 30 mL/min, calculated using standard formula.
• 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.
• Erythropoietin-analogues are allowed.
• 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.

You may not qualify if:

• Has received selinexor or another XPO1 inhibitor previously.
• 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.
• Known intolerance, hypersensitivity, or contraindication to glucocorticoids, bortezomib, lenalidomide and selinexor.
• Pregnant or breastfeeding females.
• Life expectancy of less than 6 months.
• Active, unstable cardiovascular function, as indicated by the presence of:
• Symptomatic ischemia, or
• 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
• Congestive heart failure of New York Heart Association Class ≥3 or known left ventricular ejection fraction \<40%, or
• Myocardial infarction within 6 months prior to C1D1.
• 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.
• 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).
• 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.
• Contraindication to any of the required concomitant drugs or supportive treatments.
• Patients unwilling or unable to comply with the protocol

Sponsors & Collaborators

• Ida Bruun Kristensen: lead
• Karyopharm Therapeutics Inc: collaborator
• Odense Patient Data Explorative Network: collaborator

Study Sites (11)

Aalborg University Hospital

Aalborg, Denmark

Location

Sydvestjysk Sygehus Esbjerg

Esbjerg, Denmark

Location

Regionshospitalet Gødstrup

Gødstrup, Denmark

Location

Odense University Hospital

Odense, Denmark

Location

North Estonia Medical Centre Foundation

Tallinn, 13419, Estonia

Location

Haukeland University Hospital

Bergen, Norway

Location

Førde Central Hospital

Førde, Norway

Location

Kristiansund Hospital

Kristiansund, Norway

Location

Oslo Universitets Hospital

Oslo, Norway

Location

Stavanger University Hospital

Stavanger, Norway

Location

St. Olavs University Hospital

Trondheim, Norway

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

selinexor; Tablets; Bortezomib; Lenalidomide; 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)

Dosage Forms; Pharmaceutical Preparations; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Ida B Kristensen, MB

  Odense University Hospital

  PRINCIPAL INVESTIGATOR

• Hanne Norseth, MD

  Oslo University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: January 18, 2021
• First Posted: January 22, 2021
• Study Start: August 18, 2021
• Primary Completion: August 1, 2025
• Study Completion (Estimated): June 1, 2029
• Last Updated: March 18, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

NO (6); DK (4); ES (1)