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

NCT ID: NCT04717700

Last Updated: 2025-03-18

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-08-18
• Study Completion Date: 2029-06-01

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

Detailed Description

An unrandomized phase 2 study evaluating 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.

The study will include 50 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).

Conditions

Multiple Myeloma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Selinexor 20 MG Oral Tablet

Intervention Type: DRUG

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

Bortezomib Injection

Intervention Type: DRUG

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

Lenalidomide capsule

Intervention Type: DRUG

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

Dexamethasone Oral

Intervention Type: DRUG

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

Interventions

Selinexor 20 MG Oral Tablet

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

Intervention Type: DRUG

Bortezomib Injection

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

Intervention Type: DRUG

Lenalidomide capsule

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

Intervention Type: DRUG

Dexamethasone Oral

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

Intervention Type: DRUG

Other Intervention Names

Xpovio; Velcade; Revlimid; Neofordex

Eligibility Criteria

Inclusion Criteria

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

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

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

Sponsors

Karyopharm Therapeutics Inc

INDUSTRY

Sponsor Role: collaborator

Odense Patient Data Explorative Network

OTHER

Sponsor Role: collaborator

Ida Bruun Kristensen

OTHER

Sponsor Role: lead

Responsible Party

Ida Bruun Kristensen

MD

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Ida B Kristensen, MB

Role: PRINCIPAL_INVESTIGATOR

Odense University Hospital

Hanne Norseth, MD

Role: PRINCIPAL_INVESTIGATOR

Oslo University Hospital

Locations

Aalborg University Hospital

Aalborg, , Denmark

Sydvestjysk Sygehus Esbjerg

Esbjerg, , Denmark

Regionshospitalet Gødstrup

Gødstrup, , Denmark

Odense University Hospital

Odense, , Denmark

North Estonia Medical Centre Foundation

Tallinn, , Estonia

Haukeland University Hospital

Bergen, , Norway

Førde Central Hospital

Førde, , Norway

Kristiansund Hospital

Kristiansund, , Norway

Oslo Universitets Hospital

Oslo, , Norway

Stavanger University Hospital

Stavanger, , Norway

St. Olavs University Hospital

Trondheim, , Norway

Countries

Denmark; Estonia; Norway

Other Identifiers

NMSG 29/21

Identifier Type: -

Identifier Source: org_study_id