RecruitingPhase 2NCT04414475
A Study of Selinexor (Seli) + Low-dose Dexamethasone (LDD) in Penta-refractory Multiple Myeloma (MM), Seli and Bortezomib + LDD in Triple-class Refractory MM.
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
Sponsor
Karyopharm Therapeutics Inc
Enrollment
127 participants
Start Date
Jul 1, 2020
Study Type
INTERVENTIONAL
Conditions
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.
Eligibility
Min Age: 18 Years
Inclusion Criteria11
- 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 prior to protocol version (PV) 5.0: 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 Arms Sd-40 BIW and Sd-100 QW as of PV 5.0: Participants must have RR MM and have been previously treated with \>=3 anti-MM therapies (with exposure to at least 2 PI drugs, at least 2 IMiDs, and 1 anti-CD38 monoclonal antibody), and be refractory to at least 1 drug of each class (PI/IMiD/anti-CD38). Refractory is defined as \<=25% 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.
Exclusion Criteria24
- 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 (mm\^3)
- Platelet count \< 75,000/mm\^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.
- 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.
Interventions
DRUGSelinexor
Participants will receive Selinexor oral tablets.
DRUGDexamethasone
Participants will receive Dexamethasone oral tablets.
DRUGBortezomib
Participants will receive Bortezomib SC injection.
Locations(16)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT04414475
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