Relapsed or refractory multiple myeloma (RRMM) MedDRA version: 19.1 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 free light chain (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 modified 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 support during the study. b. Patients must have: -At least a 2-week interval from the last red blood cell (RBC) transfusion prior to the Screening hemoglobin assessment, and -At least a 1-week interval from the last platelet transfusion prior to the Screening platelet assessment. However, patients may receive RBC and/or platelet transfusions as clinically indicated per in
Exclusion criteria
Exclusion criteria: 1. Has received selinexor or another XPO1 inhibitor previously. 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 neuropathy or = Grade 2 neuropathy with pain at baseline, regardless of whether or not the patient is currently receiving medication. 11. Intolerance, hypersensitivity, or contraindication to glucocorticoids. 12. Radiation, chemotherapy, or immunotherapy or any other anticancer therapy = 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) infection or HIV seropositivity. 21. Known active hepatitis A, B, or C infection; or known to be positive for hepatitis C virus ribonucleic acid (RNA) or hepatitis B virus surface antigen. 22. Any active gastrointestinal dysfunction interfering with the patient’s ability to swallow tablets, or any active gastrointestinal dysfunction that could interfere with absorption of study treatment. 23. Any active, serious psychiatric, medical, or other conditions/situations that, in the opinion of the Investigator, could interfere with treatment, compliance, or the ability to give informed consent. 24. Contraindication to any of the required concomitant drugs or supportive treatments. 25. P
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 - To compare the ORR (= PR) based on the IRC’s response outcome assessments, in patients randomized to the SVd Arm versus the Vd Arm;Secondary Objective: -To compare the incidence of any = Grade 2 neuropathy events (total = Grade 2 and separately for Grades 2, 3, and 4) in patients randomized to the SVd Arm vs patients randomized to the Vd Arm -To compare the no of patients with response = very good partial response (VGPR), = complete response (CR), = stringent complete response (sCR), or minimal residual disease (MRD) negative (for patients who achieve CR or sCR) in patients randomized to the SVd Arm versus the Vd Arm -To compare the DOR in patients randomized to the SVd Arm vs the Vd Arm -To compare OS in patients randomized to the SVd Arm vs patients randomized to the Vd Arm who do not cross over to SVdX (OS1) -To compare ORR, PFS, and DOR for patients with 1 prior anti-MM regimen versus > 1 prior anti-MM regimen in patients randomized to the SVd Arm vs the Vd Arm -To determine ORR1 (ORR during SVdX treatment) -To determine PFS1 (PFS during SVdX treatment);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. • ORR, defined as any response = PR based on the IRC’s response outcome assessments, according to the IMWG response criteria ;Timepoint(s) of evaluation of this end point: ORR for the primary analysis will be assessed on the ITT population after the last patient randomized has had the opportunity to complete at least 2 post-C1D1 MM evaluations | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: as per protocol;Secondary end point(s): Secondary efficacy endpoints: - 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) -DOR, defined as the duration of time from first occurrence of response = PR until the first date of PD or death, 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 -ORR, PFS, and DOR (for patients with 1 prior anti-MM regimen versus > 1 prior anti-MM regimen) -ORR1 (ORR for SVdX patients) -PFS1 (PFS for SVdX patients), 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 treatment -TTR, defined as time from the date of first dose of study treatment until the date of first documented response (any response and best response) per IMWG response criteria -PFS2 (PFS for patients who receive post-SVd/Vd/SVdX treatment), defined as the duration of time from the date of first dose of post-SVd/Vd/SVdX treatment until the first date of PD on post-SVd/Vd/SVdX treatment, or death due to any cause Secondary Safety Endpoints -Incidence of all grades and any = Grade 2 neuropathy events (total = Grade 2 and separately for Grades 2, 3, and 4) in patients randomized to the SVd Arm versus patients randomized to the Vd Arm. The incidence of any = Grade 2 neuropathy events will be compared between the SVd Arm and the Vd Arm (using only events that occurred prior to crossover) as a secondary endpoint using the safety population. -Safety and tolerability of study treatment based on AE reports, | — |
Countries
Austria, Belgium, Bulgaria, Canada, Czech Republic, France, Germany, Greece, Hungary, Israel, Italy, Netherlands, Poland, Russian Federation, Serbia, Spain, Ukraine, United Kingdom, United States
Contacts
Public ContactClinical Trial Information Desk
Karyopharm Therapeutics Inc.
Outcome results
None listed