Personalized Selinexor-based Therapy for Relapsed/Refractory Multiple Myeloma

Inclusion Criteria

• •1. Age ≥ 18 years
• •2. Willing and able to provide written informed consent in accordance with federal, local, and institutional guidelines. The patient must provide informed consent prior to the first screening procedure.
• •3. Eastern Cooperative Oncology Group (ECOG) performance status of ≤2
• •4. Histologically confirmed diagnosis, measurable disease and evidence of disease progression of MM after 1 or more prior lines of therapy with either of:
• •1. Documented evidence of PD after achieving at least SD for ≥ 1 cycle during a previous MM regimen (i.e., relapsed MM)
• •2. ≤ 25% response (i.e, patient never achieved ≥ MR) or PD during or within 60 days from end of the most recent MM regimen (i.e., refractory MM)
• •5. Patients must have measurable disease as defined by at least one of the following:
• •a) Serum M-protein ≥ 0.5 g/dL by serum protein electrophoresis (SPEP) or, for IgA myeloma, by quantitative IgA c) Urinary M-protein excretion at least 200 mg/24 hours d) Serum FLC ≥ 10 mg/dL, provided that FLC ratio is abnormal e) If no measurable disease by serum or urine, then the presence of a plasmacytoma of ≥ 2cm in one dimension prior to start of study can be used to follow response via radiologic imaging
• •6. Adequate hepatic function:
• •f) 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 g) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \<2.5 × ULN.
• •7. Adequate renal function as determined by serum creatinine of ≤ 2 mg/dL OR estimated creatinine clearance of ≥ 20 mL/min, calculated using the Cockcroft and Gault formula (140 - Age) • Mass (kg)/ (72 • creatinine mg/dL); multiply by 0.85 if female.
• •8. Adequate hematopoietic function within 28 days prior to C1D1: absolute neutrophil count ≥1000/mm3, hemoglobin ≥8 g/dL and platelet count ≥100,000/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).
• •1. Patients may receive hematopoietic growth factor support, including erythropoietin, darbepoetin, granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), and platelet stimulators (eg, eltrombopag, romiplostim, or interleukin-11) at any time
• •2. Patients may receive RBC and/or platelet transfusions as clinically indicated per institutional guidelines during the study.
• •9. Female patients of childbearing potential must have a negative serum pregnancy test at Screening. Female patients of childbearing potential and fertile male patients who are sexually active with a female of childbearing potential must use highly effective methods of contraception throughout the study and for 3 months following the last dose of protocol required therapies.