Refractory multiple myeloma (RMM) 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. Written informed consent in accordance with federal, local, and institutional guidelines. 2. Age = 18 years at the time of signing informed consent. 3. Measurable MM based on IMWG guidelines as defined by at least one of the following: a. Serum M-protein = 0.5 g/dL by serum electrophoresis (SPEP) or, for IgA myeloma, by quantitative IgA b. Urinary M-protein excretion = 200 mg/24 hours c. FLC = 100 mg/L, provided that the FLC ratio is abnormal. d. If serum protein electrophoresis is felt to be unreliable for routine Mprotein measurement, then quantitative Ig levels by nephelometry is acceptable. 4. Patients must have previously received = 3 anti-MM regimens including: an alkylating agent, lenalidomide, pomalidomide, bortezomib, carfilzomib, daratumumab, and a glucocorticoid. There is no upper limit on the number of prior therapies provided that all other inclusion/exclusion criteria are met. 5. MM refractory to previous treatment with one or more glucocorticoids, parenteral PI (i.e., bortezomib and/or carfilzomib), IMiD (i.e., lenalidomide and/or pomalidomide), and daratumumab. Refractory is defined as = 25% response to therapy, or progression during therapy or progression within 60 days after completion of therapy. 6. Multiple myeloma that is refractory to the patient's most recent anti- MM regimen. (Documented severe intolerance to the patient's last therapy is allowed upon approval by the Medical Monitor.) 7. Any clinically significant non-hematological toxicities (except for peripheral neuropathy as described in exclusion criterion #17) that patients experienced from treatments in previous clinical studies must have resolved to Grade =2 by Cycle 1 Day 1. 8. Adequate hepatic function within 21 days prior to Cycle 1 Day 1: total bilirubin < 2x upper limit of normal (ULN) (except patients with Gilbert's syndrome who must have a total bilirubin of < 3x ULN), AST < 2.5x ULN and ALT < 2.5x ULN. 9. Adequate renal function within 21 days prior to Cycle 1 Day 1: estimated creatinine clearance of = 20 mL/min, calculated using the formula of Cockroft and Gault. 10. Female patients of childbearing potential must agree to use 2 methods of contraception (including 1 highly effective and 1 effective method of contraception) 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 three months following the last dose of study treatment. 11. Eastern Cooperative Oncology Group (ECOG) Performance Status of = 2. 12. Adequate hematopoietic function within 21 days prior to Cycle 1 Day 1 (See Exclusion Criterion #20 for transfusion washout periods for RBCs and platelets): a. Total WBC count = 1,000/mm3 b. ANC = 1000/mm3 c. Platelet count = 75,000/mm3 (patients in whom <50% of bone marrow nucleated cells are plasma cells) or = 50,000/mm3 (patients in whom = 50% of bone marrow nucleated cells are plasma cells. [Platelet transfusions <1 week prior to Cycle 1 Day 1 are prohibited (see below).] 13. Hemoglobin level = 8.5 g/dL. In certain cases, patients with st
Exclusion criteria
Exclusion criteria: 1. Active smoldering MM. 2. Active plasma cell leukemia. 3. Documented systemic amyloid light chain amyloidosis. 4. Active central nervous system (CNS) MM. 5. Pregnancy or breastfeeding. 6. Radiation, chemotherapy, or immunotherapy or any other anticancer therapy = 2 weeks prior to Cycle 1 Day 1, and radio-immunotherapy 6 weeks prior to Cycle 1 Day 1. 7. Active graft vs. host disease (after allogeneic stem cell transplantation) at Cycle 1 Day 1 8. Life expectancy of 5 years previously and without evidence of recurrence will be allowed. 16. Active GI dysfunction interfering with the ability to swallow tablets, or any GI dysfunction that could interfere with absorption of study treatment. 17. Grade = 3 peripheral neuropathy, and Grade = 2 painful neuropathy, within 21 days prior to Cycle 1 Day 1. 18. Serious, active psychiatric or medical conditions which, in the opinion of the Investigator, could interfere with treatment. 19. Participation in an investigational anti-cancer study within 21 days prior to Cycle 1 Day 1. 20. Receipt of transfusions as follows: a. Platelet infusion within 1 week prior to Cycle 1 Day 1. b. RBC transfusion within 2 weeks prior to Cycle 1 Day 1. 21. Receipt of the following blood growth factors within 2 weeks prior to Cycle 1 Day 1: Granulocyte colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor (GM-CSF), erythropoietin (EPO), or megakaryocyte growth factor. 22. Known intolerance to or contraindication for glucocorticoid therapy at Cycle 1 Day 1. 23. Prior exposure to a SINE compound, including Selinexor. 24. Unable or unwilling to comply with protocol requirements, including providing a 24-hour urine samples at the required study time points.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Overall Response Rate (ORR); Timepoint(s) of evaluation of this end point: The primary statistical analysis of efficacy will be performed on ORR (achievement of PR, VGPR, CR or sCR) for the mITT population after the last patient has completed 1 cycle. ; Main Objective: Evaluate the efficacy (overall response rate [ORR]) for treatment with selinexor 80 mg plus low-dose dexamethasone (20 mg) (Sd) twice weekly (four-week cycles) in patients with MM previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, and daratumumab; and refractory to prior treatment with glucocorticoids, an immunomodulatory agent (IMiD), a proteasome inhibitor (PI), and the anti-CD38 mAb daratumumab (herein referred to as penta-refractory MM). ORR will include patients who experience partial response (PR), very good partial response (VGPR), complete response (CR), or stringent complete response (sCR), based on International Myeloma Working Group (IMWG) response criteria (Kumar 2016) for patients with pentarefractory MM in Part 2 (Expansion). ; Secondary Objective: The following endpoints will be analyzed separately for (a) Part1 patients with quad-refractory MM, (b) Part1 patients with pentarefractory MM, and (c) Part2 (expansion) patients with penta-refractory MM. Additionally, analyses of safety and tolerability will be performed on the overall population of patients from Parts1 and2 who received at least one dose of study treatment. - Duration of response - Clinical Benefit Rate and duration of clinical benefit (Duration from first observation of at least MR to time of disease progression or death due to disease progression, whichever occurs first. - Disease Control Rate - Progression Free Survival - Time to Progression obtained with selinexor plus dexamethasone vs. TTP on most recent p | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Duration of response; clinical benefit rate and duration of clinical benefit; disease control rate; progression free survival; time to progression obtained with selinexor plus dexamethasone versus TTP on most recent prior therapy; Time to Next Treatment (TTNT = Duration from start of study treatment to start of next anti-MM treatment or death due to disease progression, whichever occurs first), overall survival; quality of life using FACT-MM. ;Timepoint(s) of evaluation of this end point: The secondary analysis of efficacy will be performed after the last patient has completed 1 cycle. | — |
Countries
Austria, Belgium, France, Germany, Greece, United States
Contacts
Public ContactClinical Trials Information Desk
Karyopharm Therapeutics Inc.
Outcome results
None listed