Relapsed or refractory multiple myeloma (RRMM) MedDRA version: 20.0 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. Histologically confirmed MM with measurable disease per IMWG guidelines as defined by at least 1 of the following: a. Serum M-protein = 0.5 g/dL (> 5 g/L) by serum protein electrophoresis (SPEP) or for immunoglobulin (Ig) A myeloma, by quantitative serum IgA levels; or b. Urinary M-protein excretion at least 200 mg/24 hours; or c. Serum FLC = 100 mg/L, provided that the serum FLC ratio is abnormal (normal FLC ratio: 0.26 to 1.65). 2. Had at least 1 prior anti-MM regimen and no more than 3 prior anti-MM regimens. Induction therapy followed by stem cell transplant and consolidation/maintenance therapy will be considered as 1 anti-MM regimen. 3. Documented evidence of progressive MM (based on the Investigator's determination according to the IMWG response criteria) on or after their most recent regimen. 4. Prior treatment with bortezomib or other PI is allowed, provided all of the following criteria are met: -Best response achieved with prior bortezomib at any time was = PR and with the last PI therapy (alone or in combination) was = PR, AND -Participant did not discontinue bortezomib due to Grade = 3 related toxicity, AND -Must have had at least a 6-month PI-treatment-free interval prior to C1D1 of study treatment. 5. Must have an ECOG Status score of 0, 1, or 2. 6. Written informed consent in accordance with federal, local, and institutional guidelines. 7. Age = 18 years. 8. Resolution of any clinically significant non-hematological toxicities (if any) from previous treatments to Grade = 1 by C1D1. Patients with chronic, stable Grade 2 non-hematological toxicities may be included following approval from the Medical Monitor. 9. Adequate hepatic function within 28 days prior to C1D1: a. Total bilirubin < 1.5 × upper limit of normal (ULN) (except patients with Gilbert’s syndrome who must have a total bilirubin of < 3 × ULN), and b. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) normal to < 2 × ULN. 10. Adequate renal function within 28 days prior to C1D1 (estimated creatinine clearance [CrCl] of = 20 mL/min, calculated using the formula of Cockroft and Gault): (140-Age) × Mass (kg)/(72 × creatinine mg/dL) Multiply by 0.85 if the patient is female, or if CrCl is = 20 mL/min as measured by 24-hour urine collection. 11. Adequate hematopoietic function within 7 days prior to C1D1: total white blood cell (WBC) count = 1500/mm3, absolute neutrophil count = 1000/mm3, hemoglobin = 8.5 g/dL and platelet count = 75,000/mm3 (patients for whom < 50% of bone marrow nucleated cells are plasma cells) or = 50,000/mm3 (patients for whom = 50% of bone marrow nucleated cells are plasma cells). a. Patients receiving hematopoietic growth factor support, including erythropoietin, darbepoetin, granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), and platelet stimulators (e.g., eltrombopag, romiplostim, or interleukin-11) must have a 2-week interval between growth factor support and the Screening assessments, but they may receive growth factor supp
Exclusion criteria
Exclusion criteria: 1. Prior exposure to a SINE compound, including selinexor. 2. Prior malignancy that required treatment, or has shown evidence of recurrence (except for non-melanoma skin cancer or adequately treated cervical carcinoma in situ) during the 5 years prior to randomization. Cancer treated with curative intent for > 5 years previously and without evidence of recurrence will be allowed. 3. Has any concurrent medical condition or disease (e.g., uncontrolled active hypertension, uncontrolled active diabetes, active systemic infection, etc.) that is likely to interfere with study procedures. 4. Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within 1 week prior to C1D1. Patients on prophylactic antibiotics or with a controlled infection within 1 week prior to C1D1 are acceptable. 5. Active plasma cell leukemia. 6. Documented systemic light chain amyloidosis. 7. MM involving the central nervous system. 8. Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome. 9. Spinal cord compression. 10. 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. 11. Known intolerance, hypersensitivity, or contraindication to glucocorticoids. 12. Radiation, chemotherapy, or immunotherapy or any other anticancer therapy (including investigational therapies) = 2 weeks prior to C1D1. Localized radiation to a single site at least 1 week before C1D1 is permitted. Glucocorticoids within 2 weeks of C1D1 are permitted. Patients on long-term glucocorticoids during Screening do not require a washout period but must be able to tolerate the specified dexamethasone dose in this study. 13. Prior autologous stem cell transplantation < 1 month or allogeneic stem cell transplantation < 4 months prior to C1D1. 14. Active graft versus host disease (after allogeneic stem cell transplantation) at C1D1. 15. Pregnant or breastfeeding females. 16. BSA < 1.4 m2 at baseline, calculated by the Dubois (Dubois 1916) or Mosteller (Mosteller, 1987) method. 17. Life expectancy of < 4 months. 18. Major surgery within 4 weeks prior to C1D1. 19. Active, unstable cardiovascular function: a. Symptomatic ischemia, or b. Uncontrolled clinically significant conduction abnormalities (e.g., patients with ventricular tachycardia on anti-arrhythmics are excluded; patients with first-degree atrioventricular block or asymptomatic left anterior fascicular block/right bundle branch block will not be excluded), or c. Congestive heart failure of New York Heart Association Class = 3 or known left ventricular ejection fraction < 40%, or d. Myocardial infarction within 3 months prior to C1D1. 20. Known active human immunodeficiency virus (HIV) infe
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - To compare PFS based on the Independent Review Committee’s (IRC’s) disease outcome assessments in patients randomized to the SVd Arm versus the Vd Arm ; Secondary Objective: - To compare the ORR (= PR) based on the IRC’s response outcome assessments, in patients randomized to the SVd Arm versus the Vd Arm -To compare the incidence of any Grade = 2 peripheral neuropathy events in patients randomized to the SVd Arm vs patients randomized to the Vd Arm -To compare the no of patients with response = VGPR, = CR, =sCR, or MRD negative (for patients who achieve CR or sCR) in patients randomized to the SVd Arm versus the Vd Arm -To compare OS in all patients randomized to the SVd Arm vs the Vd Arm -To compare the DOR in patients randomized to the SVd Arm vs the Vd Arm -To determine ORR1 (ORR during SVdX treatment only) -To determine PFS1 (PFS during SVdX treatment only) - To compare time-to-next-treatment (TTNT) in patients randomized to the SVd Arm versus the Vd Arm who receive post SVd/Vd/SVdX/SdX treatment - To compare time-to-response (TTR) in patients randomized to the SVd Arm versus the Vd Arm ; Primary end point(s): PFS, defined as time from date of randomization until the first date of PD, per IMWG response criteria, or death due to any cause, whichever occurs first. For the purposes of PFS determination, PD will be determined by the IRC. ;Timepoint(s) of evaluation of this end point: The primary End Point is PFS which is defined as either date of Death or date of Disease Progression when approved by the IRC according to the IMWG criteria | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: as per protocol; Secondary end point(s): Secondary efficacy endpoints Key Secondary efficacy endpoints - ORR, defined as any response = PR (ie, PR, VGPR, CR or sCR) based on the IRC's response outcome assessments, according to the IMWG response criteria. All changes in MM disease assessments will be based on baseline MM disease assessments. - Response rates at any time prior to PD or death due to any cause, pooled and separately for the following responses: = VGPR, = CR = sCR, or MRD negative (for patients who achieve CR or sCR) Non-Key Secondary Efficacy Endpoints -OS, defined as time to death or lost to follow-up, measured from the date of randomization until death due to any cause or until lost to follow-up, for all patients -DOR, defined as the duration of time from first occurrence of IRC-confirmed response = PR until the first date of IRC-confirmed PD or death due to any cause, whichever occurs first -OS1, defined as time to death, measured from date of randomization until death due to any cause, for patients randomized to the Vd Arm who do not cross over to SVdX or SdX; Vd patients who cross over will be censored at the date of crossover -ORR, PFS, and DOR (for patients with 1 prior anti-MM regimen versus > 1 prior anti-MM regimen) -ORR1 (ORR for SVdX patients only) -PFS1 (PFS for SVdX patients only), defined as the duration of time from date of first dose of SVd treatment after crossover from the Vd Arm until the first date of PD, or death due to any cause -TTNT, defined as duration of time from date of last dose of study treatment until the date of first dose of post-SVd/Vd/SVdX/SdX treatment -TTR, defined as duration of time from randomization until the date of first documented response (= | — |
Countries
Australia, Austria, Belgium, Bulgaria, Canada, Czech Republic, France, Germany, Greece, Hungary, India, Israel, Italy, Poland, Romania, Russian Federation, Serbia, Spain, Ukraine, United Kingdom, United States
Contacts
Public ContactClinical Trial Information Desk
Karyopharm Therapeutics Inc.
Outcome results
None listed