Selinexor (KPT-330) in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL)

Exclusion Criteria

• •Participants who are pregnant or lactating.
• •Primary mediastinal (thymic) large B-cell lymphoma (PMBL)
• •Participants must not be eligible for high-dose chemotherapy with autologous stem cell transplantation rescue (Investigator must provide detailed documentation for ineligibility).
• •Participants who have not recovered to Grade ≤1 clinically significant adverse events, or to their baseline, from their most recent systemic anti-DLBCL therapy.
• •Major surgery within 2 weeks of first dose of study treatment.
• •Participants with active hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infections.
• •Psychiatric illness or substance use that would prevent the participant from giving informed consent or being compliant with the study procedures.
• •Any of the following laboratory abnormalities:
• •(i) A circulating lymphocyte count of \>50,000/L. (ii) Hepatic dysfunction: bilirubin \>2.0 times the upper limit of normal (ULN) (except participants with Gilbert's syndrome: total bilirubin of \>3\*ULN) and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \>2.5 times ULN. In participants with known liver involvement of their DLBCL, AST and ALT \>5\*ULN.
• •(iii) Severe renal dysfunction: estimated creatinine clearance of \<30 mL/min, measured in 24-hour urine or calculated using the formula of Cockroft and Gault \[(140-Age)\*Mass (kg)/(72\*creatinine mg/dL); multiply by 0.85 if female\].
• •Any life-threatening illness, medical condition, or organ system dysfunction which, in the Investigator's opinion, could compromise the participant's safety.
• •Participants with active graft-versus-host disease after allogeneic stem cell transplantation. At least 4 months must have elapsed since completion of allogeneic stem cell transplantation.
• •Uncontrolled (i.e., clinically unstable) infection requiring parenteral antibiotics, antivirals, or antifungals on Cycle 1 Day 1; however, prophylactic use of these agents is acceptable even if parenteral.
• •Participants unable to swallow tablets, participants with malabsorption syndrome, or any other gastrointestinal disease or gastrointestinal dysfunction that could interfere with absorption of study treatment.
• •For participants whose most recent systemic anti-DLBCL therapy induced a PR or CR: Radiation, chemotherapy, immunotherapy, radio-immunotherapy, or any other anticancer therapy other than glucocorticoids \<60 days or \<14 weeks prior to Cycle 1 Day 1.
• •Known central nervous system lymphoma or meningeal involvement.
• •DLBCL with mucosa-associated lymphoid tissue \[MALT\] lymphoma, composite lymphoma (Hodgkin's lymphoma+NHL), or DLBCL transformed from diseases other than indolent NHL.
• •Unstable cardiovascular function:
• •(i) Symptomatic ischemia, or (ii) Uncontrolled clinically significant conduction abnormalities (i.e., ventricular tachycardia on anti-arrhythmia are excluded; 1st degree atrioventricular block or asymptomatic left anterior fascicular block /right bundle branch block will not be excluded), or (iii) Congestive heart failure of New York Heart Association Class ≥3, or (iv) Myocardial infarction within 3 months.
• •Participants with a BSA \<1.4 m\^2 as calculated per Dubois 1916 or Mosteller 1987.
• •Any of the following laboratory abnormalities:
• •(i) Absolute neutrophil count (ANC) \<1000 cells/mm\^3 or platelet count \<75,000/mm\^3 during screening and on Cycle 1 Day 1. Use of granulocyte-stimulating factors and platelet growth factors prior to and during the study is acceptable.
• •(ii) Hematopoietic dysfunction: hemoglobin \< 10.0 g/dL within 14 days of and including Cycle 1 Day 1 and/or patients receiving red blood cell (RBC) transfusion within 14 days of and including Cycle 1 Day 1.
• •Participants who have been committed to an institution by official or judicial order.
• •Participants with dependency on the Sponsor, Investigator or study site.
• •Participants with active HBV, HVC, or HIV infections. Participants with active HBV are allowed if antiviral therapy for hepatitis B has been given for \>8 weeks and viral load is \<100 International units per milliliters (IU/mL) prior to first dose of study treatment. Participants with known history of HCV or found to be HCV antibody positive on screening, are allowed if there is documentation of negative viral load per institutional standard. Participants with HIV who have CD4+T-cell counts ≥350 cells/microliter (mcL), negative viral load per institutional standard, and no history of acquired immune deficiency syndrome (AIDS)-defining opportunistic infections in the last year are allowed.
• •Known active central nervous system lymphoma or meningeal involvement. Participants with a history of CNS disease treated into remission may be enrolled.
• •DLBCL with MALT lymphoma, composite lymphoma (Hodgkin's lymphoma + NHL), DLBCL arising from CLL (Richter's transformation), or high-grade B-cell lymphoma.
• •Received strong cytochrome P450 3A (CYP3A) inhibitors ≤7 days prior to Day 1 dosing or strong CYP3A inducers ≤14 days prior to Day 1 dosing.