Penta-refractory multiple myeloma and triple-class refractory multiple myeloma MedDRA version: 21.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864
Conditions
Sponsors
Karyopharm Therapeutics Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age =18 years at the time of signing informed consent. 2. Written informed consent in accordance with federal, local, and institutional guidelines. 3. Measurable multiple myeloma (MM) based on International Myeloma Working Group (IMWG) guidelines as defined by at least one of the following: a. Serum M-protein =0.5 g/dL by serum protein electrophoresis (SPEP) or, for Immunoglobulin (Ig) A myeloma, by quantitative IgA. b. Urinary M-protein excretion =200 mg/24 hours. c. Free light chain (FLC) =100 mg/L, provided that the FLC ratio is abnormal. 4. Only for arms Sd-40 BIW, Sd-100 QW and Sd-80 BIW: Patients 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 PIs, at least 2 immunomodulatory agent (IMiDs), and 1 anti-CD38 monoclonal antibody. Refractory is defined as =25% response to therapy, or progression during therapy or progression within 60 days after completion of therapy. 5. Only for arm SVd: Patients 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. 6. Eastern Cooperative Oncology Group (ECOG) performance status of =2. 7. Female patients of childbearing potential must agree to use dual methods of contraception and have a negative serum pregnancy test at screening, and male patients must use an effective barrier method of contraception if sexually active with a female of childbearing potential. For both male and female patients, 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. 8. Patient agrees to provide bone marrow aspirate to be used for genetic testing of DNA and RNA. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 54 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 80
Exclusion criteria
Exclusion criteria: 1. Active plasma cell leukemia. 2. Documented systemic amyloid light chain amyloidosis. 3. Active central nervous system multiple myeloma (MM). 4. 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 patient is currently receiving medication. 5. 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). 6. Active graft vs. host disease (after allogeneic stem cell transplantation) at C1D1. 7. Ongoing clinically significant non-hematological toxicities from prior treatments that are Grade >2 at C1D1. 8. Inadequate hepatic function defined as total bilirubin =2x upper limit of normal (ULN) (=3x ULN for patients with Gilbert’s syndrome), aspartate transaminase (AST) =2.5x ULN, and alanine transaminase (ALT) =2.5x ULN. 9. Inadequate renal function defined as estimated creatinine clearance of <20 mL/min, calculated using the formula of Cockroft and Gault. 10. Inadequate hematopoietic function defined as the following: a. Absolute neutrophil count (ANC) <1000/mm3. b. Platelet count <75,000/mm3 c. Hemoglobin (Hb) level <8.5 g/dL 11. Life expectancy of <4 months, based on the opinion of the Investigator. 12. Major surgery within 4 weeks prior to C1D1. 13. Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within 1 week prior to first dose. 14. Active gastrointestinal dysfunction interfering with the ability to swallow tablets, or any gastrointestinal dysfunction that could interfere with absorption of the study treatment. 15. Known active hepatitis A, B, or C infection; or known to be positive for hepatitis C virus RNA or hepatitis B virus surface antigen. 16. Receipt of red blood cells (RBC) transfusions within 2 weeks of C1D1. 17. Receipt of platelet transfusion within 1 week of C1D1. 18. 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. 19. Female patients who are pregnant or lactating. 20. Known intolerance to or contraindication for glucocorticoid therapy at C1D1. 21. Concurrent therapy with approved or investigational anticancer therapeutic including topical therapies. 22. Prior exposure to a SINE compound, including selinexor. 23. Serious, active psychiatric or medical conditions which, in the opinion of the Investigator or Sponsor, could interfere with the participation in the study. 24. Contraindication to any of the required concomitant drugs or supportive treatments.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of treatment of the 4 arms: - Selinexor 40 mg plus dexamethasone 20 mg in patients with penta-refractory multiple myeloma twice/week, - Selinexor 80 mg plus dexamethasone 20 mg in patients with penta-refractory multiple myeloma twice/week, - Selinexor 100 mg plus dexamethasone 40mg in patients with penta-refractory multiple myeloma once/week, - Selinexor 100 mg in combination with dexamethasone 40 mg and bortezomib 1.3 mg/m2 in patients with triple-class refractory multiple myeloma, once/week (without week 5 dosing).;Secondary Objective: - To assess the antitumor activity of the 4 arms; - To assess the safety and tolerability of treatment of the 4 arms.;Primary end point(s): Overall response rate (ORR) defined as the proportion of patients who achieve stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) based on International Myeloma Working Group (IMWG) response criteria will be analyzed separately for each arm.;Timepoint(s) of evaluation of this end point: From baseline to the end of trial | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. The following endpoints will be analyzed separately for each arm: • Duration of response (DOR) • Clinical benefit rate (CBR) • Disease control rate (DCR) • Progression-free survival (PFS) • Overall survival (OS) • Time to next treatment (TTNT) 2. The safety and tolerability of study drug will be evaluated based on AE reports, vital signs, and clinical laboratory results by means of the occurrence, nature, and severity of AEs as categorized by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0.;Timepoint(s) of evaluation of this end point: From baseline to the end of trial | — |
Countries
Greece, Israel
Contacts
Public ContactClinical Trial Information Desk
Karyopharm Therapeutics Inc.
Outcome results
None listed