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 vizsgálat adatai

Ki végzi

Karyopharm Therapeutics Inc

Azonosító

NCT04414475EU 2024-511608-18-00

A regiszteradat frissítve

2026. október 29.

Eredeti leírás

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.A teljes eredeti leírásKevesebb

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

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.

Bevonási feltételek: 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.

Kizáró feltételek: 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); Ongoing clinically significant non-hematological toxicities from prior treatments that are Grade greater than (>) 2 at C1D1; Major surgery within 4 weeks prior to C1D1; Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within 1 week prior to first dose; Concurrent therapy with approved or investigational anticancer therapeutic including topical therapies; Prior exposure to a SINE compound, including selinexor; Contraindication to any of the required concomitant drugs or supportive treatments; Active graft vs. host disease (after allogeneic stem cell transplantation) at C1D1; Known active hepatitis A, B, or C infection; or known to be positive for hepatitis C virus RNA or hepatitis B virus surface antigen; Known intolerance, hypersensitivity, or contraindication to glucocorticoid therapy at C1D1; 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; 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; Active plasma cell leukemia; Documented systemic amyloid light chain amyloidosis; Active central nervous system MM; Life expectancy of < 4 months, based on the opinion of the Investigator; Active gastrointestinal dysfunction interfering with the ability to swallow tablets, or any gastrointestinal dysfunction that could interfere with absorption of the study treatment; Female participants who are pregnant or lactating.

ClinicalTrials.gov NCT04414475 · EU CTIS 2024-511608-18-00