A Study of Selinexor (Seli) + Low-dose Dexamethasone (LDD) in Penta-refractory Multiple Myeloma (MM), Seli and Bortezomib + LDD in Triple-class Refractory MM, and Seli and Pomalidomide + LDD in Relapsed Refractory MM

Multiple Myeloma, Refractory Clinical Trial

Official title:

A Phase 2b, Open-label Study of Selinexor Plus Low-dose Dexamethasone (Sd) in Patients With Penta-refractory Multiple Myeloma (MM), Selinexor and Bortezomib Plus Low-dose Dexamethasone (SVd) in Patients With Triple-class Refractory MM, and Selinexor and Pomalidomide Plus Low-dose Dexamethasone (SPd) in Patients With Relapsed Refractory MM.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04414475
• Other study ID #: XPORT-MM-028
• Status: Recruiting
• Phase: Phase 2
• Start date: July 1, 2020
• Est. completion date: June 30, 2025

Study information

• Verified date: February 2024
• Source: Karyopharm Therapeutics Inc
• Contact: Karyopharm Medical Information
• Phone: (888) 209-9326
• Email: clinicaltrials[@]karyopharm.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 or selinexor and pomalidomide plus low-dose dexamethasone in participants with relapsed and/or refractory multiple myeloma.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 141
• Est. completion date: June 30, 2025
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

• Only for arm SPd: relapsed or refractory pomalidomide naïve MM with: documented evidence of progressive disease (PD) after achieving at least SD for =1 cycle during a previous MM regimen (i.e., relapsed MM); =25% response (i.e., patients never achieved =MR) or PD during or within 60 days from the end of the most recent MM regimen (i.e., refractory MM); previously undergone =2 cycles of lenalidomide and a PI (in separate therapeutic regimens [not for maintenance] or in combination).

• Only for arm SPd: only patients that were prescribed with pomalidomide as per standard of care will be enrolled in this arm at the discretion of the Investigators.

• Only for arm SPd: adequate hematopoietic function within 28 days prior to C1D1: total white blood cell (WBC) count =1,500/mm³, ANC =1,000/mm³, hemoglobin (Hb) =8.0 g/dL, Platelet count =100,000/mm³

• 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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Multiple Myeloma, Refractory
• Neoplasms, Plasma Cell

Intervention

Drug:
• Selinexor
Participants will receive Selinexor oral tablets.
• Dexamethasone
Participants will receive Dexamethasone oral tablets.
• Bortezomib
Participants will receive Bortezomib SC injection.
• Pomalidomide
Participants will receive Pomalidomide oral tablets.

Locations

Country	Name	City	State
Greece	General Hospital of Athens "Evaggelismos"	Athens	Attiki
Greece	General Hospital of Athens "ALEXANDRA"	Attiki	Athens
Greece	University General Hospital of Patras	Patra	Achaia
Greece	Theageneion Cancer Hospital	Thessaloniki
Israel	Emek Medical Center	Afula
Israel	Assuta Ashdod Medical Center	Ashdod
Israel	Barzilai Medical Center	Ashkelon
Israel	Soroka University Medical Center	Beer-Sheva
Israel	Bnai-Zion Medical Center	Haifa
Israel	Rambam Health Care Campus	Haifa
Israel	Hadassah Medical Center	Jerusalem
Israel	Shaare Zedek Medical Center	Jerusalem
Israel	Meir Medical Center	Kfar Saba
Israel	Rabin Medical Center (Beilinson Hospital)	Petah Tikva
Israel	The Chaim Sheba Medical Center at Tel HaShomer	Ramat Gan
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv

Sponsors (1)

Lead Sponsor	Collaborator
Karyopharm Therapeutics Inc

Countries where clinical trial is conducted

Greece,  Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response Rate (ORR)		From the date of randomization up to death (approximately 14 months)
Secondary	Duration of Response (DOR)		From the date of randomization to first disease progression or death (approximately 14 months)
Secondary	Clinical Benefit Rate (CBR)		From the date of randomization up to death (approximately 14 months)
Secondary	Disease control rate (DCR)		From the date of randomization up to death (approximately 14 months)
Secondary	Progression-Free Survival (PFS)		From the date of randomization to first disease progression or death (approximately 14 months)
Secondary	Overall Survival (OS)		From the date of randomization up to death (approximately 14 months)
Secondary	Time to Next Treatment (TTNT)		From the date of first dose up to death (approximately 14 months)
Secondary	Number of Participants with Adverse Events (AE)		From start of study drug administration up to follow-up (approximately 3 months)