A Study 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

Sponsor

Karyopharm Therapeutics Inc (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04414475

Collaborator

(none)

134

Enrollment

Locations

Arms

Anticipated Duration (Months)

8.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma, Refractory	Drug: Selinexor Drug: Dexamethasone Drug: Bortezomib	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

134 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 2b, Open-label, Multi-arm Clinical Trial of Selinexor Plus Low-dose Dexamethasone (Sd) in Patients With Penta-refractory Multiple Myeloma or Selinexor and Bortezomib Plus Low-dose Dexamethasone (SVd) in Patients With Triple-class Refractory Multiple Myeloma

Actual Study Start Date :

Jul 1, 2020

Anticipated Primary Completion Date :

Jun 30, 2024

Anticipated Study Completion Date :

Jun 30, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Selinexor + Low-dose Dexamethasone (Sd-40 BIW) Participants will receive fixed dose of 40 milligram (mg) of Selinexor oral tablet followed by 20 mg of low-dose Dexamethasone oral tablet twice weekly (BIW) on Days 1, 3, 8, 10, 15, 17, 22, and 24 of each 28-day cycle.	Drug: Selinexor Participants will receive Selinexor oral tablets. Other Names: KPT-330 XPOVIO Drug: Dexamethasone Participants will receive Dexamethasone oral tablets. Other Names: Decadron
Experimental: Selinexor + Low-dose Dexamethasone (Sd-100 QW) Participants will receive fixed dose of 100 mg of Selinexor oral tablet followed by 40 mg of low-dose Dexamethasone oral tablet once weekly (QW) on Days 1, 8, 15, and 22 of each 28-day cycle. (Dexamethasone may be given as 20 mg on days 1 and 2 of each week).	Drug: Selinexor Participants will receive Selinexor oral tablets. Other Names: KPT-330 XPOVIO Drug: Dexamethasone Participants will receive Dexamethasone oral tablets. Other Names: Decadron
Experimental: Selinexor + Low-dose Dexamethasone (Sd-80 BIW) Participants will receive fixed dose of 80 mg of Selinexor oral tablet followed by 20 mg of low-dose Dexamethasone oral tablet BIW on Days 1, 3, 8, 10,15, 17, 22, and 24 of each 28-day cycle.	Drug: Selinexor Participants will receive Selinexor oral tablets. Other Names: KPT-330 XPOVIO Drug: Dexamethasone Participants will receive Dexamethasone oral tablets. Other Names: Decadron
Experimental: Selinexor + Bortezomib + Dexamethasone (SVd) Participants will receive fixed dose of 100 mg of Selinexor oral tablet on Days 1, 8, 15, 22, and 29 followed by 1.3 milligram per square-meter (mg/m^2) of Bortezomib subcutaneous (SC) injection on Days 1, 8, 15, and 22 and followed by 40 mg of low-dose Dexamethasone oral tablet on Days 1, 8, 15, 22, and 29 of each 35-day cycle (Dexamethasone dose may be split to 20 mg on days 1 and 2).	Drug: Selinexor Participants will receive Selinexor oral tablets. Other Names: KPT-330 XPOVIO Drug: Dexamethasone Participants will receive Dexamethasone oral tablets. Other Names: Decadron Drug: Bortezomib Participants will receive Bortezomib SC injection. Other Names: Velcade

Outcome Measures

Primary Outcome Measures

Overall Response Rate (ORR) [From the date of randomization up to death (approximately 14 months)]

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

Serum M-protein ≥ 0.5 gram per deciliter (g/dL) by serum protein electrophoresis (SPEP) or, for Immunoglobulin (Ig) A myeloma, by quantitative IgA.
Urinary M-protein excretion ≥ 200 mg/24 hours.
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.
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:

Absolute neutrophil count (ANC) < 1000/cubic millimeter (mm3)
Platelet count < 75,000/mm3
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University General Hospital of Patras	Patra	Achaia	Greece	2654
2	General Hospital of Athens "ALEXANDRA"	Attiki	Athens	Greece	11528
3	General Hospital of Athens "Evaggelismos"	Athens	Attiki	Greece	10676
4	Theageneion Cancer Hospital	Thessaloniki		Greece	54007
5	Emek Medical Center	Afula		Israel	1834111
6	Assuta Ashdod Medical Center	Ashdod		Israel	7747629
7	Barzilai Medical Center	Ashkelon		Israel	7830604
8	Soroka University Medical Center	Beer-Sheva		Israel
9	Bnai-Zion Medical Center	Haifa		Israel	3108
10	Rambam Health Care Campus	Haifa		Israel	3109601
11	Shaare Zedek Medical Center	Jerusalem		Israel	9103102
12	Hadassah Medical Center	Jerusalem		Israel	9112001
13	Meir Medical Center	Kfar Saba		Israel	4428164
14	Rabin Medical Center (Beilinson Hospital)	Petah Tikva		Israel	49100
15	The Chaim Sheba Medical Center at Tel HaShomer	Ramat Gan		Israel	52621
16	Tel Aviv Sourasky Medical Center	Tel Aviv		Israel	64239