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

• Sponsor: Ida Bruun Kristensen (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT04717700
• Collaborator: Karyopharm Therapeutics Inc (Industry), Odense Patient Data Explorative Network (Other)
• Enrollment: 100
• Locations: 11
• Arms: 2
• Anticipated Duration (Months): 93.4
• Patients Per Site: 9.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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).

Study Design

• Study Type: Interventional
• Anticipated 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
• Actual Study Start Date: Aug 18, 2021
• Anticipated Primary Completion Date: Jun 1, 2024
• Anticipated Study Completion Date: Jun 1, 2029

Arms and Interventions

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 Names: Velcade ; Drug: Lenalidomide capsule; Comparing an alternating regimen of selinexor-lenalidomide/bortezomib-dexamethasone to standard bortezomib-lenalidomide-dexamethasone; Other Names: Revlimid ; Drug: Dexamethasone Oral; Comparing an alternating regimen of selinexor-lenalidomide/bortezomib-dexamethasone to standard bortezomib-lenalidomide-dexamethasone; Other Names: 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 Names: Xpovio ; Drug: Bortezomib Injection; Comparing an alternating regimen of selinexor-lenalidomide/bortezomib-dexamethasone to standard bortezomib-lenalidomide-dexamethasone; Other Names: Velcade ; Drug: Lenalidomide capsule; Comparing an alternating regimen of selinexor-lenalidomide/bortezomib-dexamethasone to standard bortezomib-lenalidomide-dexamethasone; Other Names: Revlimid ; Drug: Dexamethasone Oral; Comparing an alternating regimen of selinexor-lenalidomide/bortezomib-dexamethasone to standard bortezomib-lenalidomide-dexamethasone; Other Names: Neofordex

Outcome Measures

Primary Outcome Measures

1. Increased ORR in arm B (defined as ≥PR) at end of induction, defined according to IMWG response criteria [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 [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 [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 [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 [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 [Estimated monthly during the first 64 weeks]

   Time to at least VGPR from start of treatment

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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:

8. 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

9. Alanine aminotransferase (ALT) normal to <2 × ULN.

10. Adequate renal function within 7 days prior to C1D1 as determined by estimated GFR of ≥ 30 mL/min, calculated using standard formula.

11. 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.

12. Erythropoietin-analogues are allowed.

13. 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.

1. 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.

2. Patients must be able to take prophylactic anticoagulation as recommended by study

3. 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:

7. Symptomatic ischemia, or

8. 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

9. Congestive heart failure of New York Heart Association Class ≥3 or known left ventricular ejection fraction <40%, or

10. Myocardial infarction within 6 months prior to C1D1.

11. 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.

12. 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).

13. 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.

14. Contraindication to any of the required concomitant drugs or supportive treatments.

15. Patients unwilling or unable to comply with the protocol

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Aalborg University Hospital	Aalborg		Denmark
2	Sydvestjysk Sygehus Esbjerg	Esbjerg		Denmark
3	Regionshospitalet Holstebro	Holstebro		Denmark
4	Odense University Hospital	Odense		Denmark
5	North Estonia Medical Centre Foundation	Tallinn		Estonia	13419
6	Haukeland University Hospital	Bergen		Norway
7	Førde Central Hospital	Førde		Norway
8	Kristiansund Hospital	Kristiansund		Norway
9	Oslo Universitets Hospital	Oslo		Norway
10	Stavanger University Hospital	Stavanger		Norway
11	St. Olavs University Hospital	Trondheim		Norway

Sponsors and Collaborators

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

Investigators

• Principal Investigator: Ida B Kristensen, MB, Odense University Hospital
• Principal Investigator: Hanne Norseth, MD, Oslo University Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ida Bruun Kristensen, MD, Odense University Hospital
• ClinicalTrials.gov Identifier: NCT04717700
• Other Study ID Numbers: NMSG 29/21
• First Posted: Jan 22, 2021
• Last Update Posted: Apr 25, 2022
• Last Verified: Apr 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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, MD, Odense University Hospital: selinexor
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Dexamethasone; Lenalidomide; Bortezomib

Study Results

No Results Posted as of Apr 25, 2022