Selinexor and Combination Chemotherapy in Treating Patients with Advanced B Cell Non-Hodgkin Lymphoma or Newly Diagnosed Diffuse Large B Cell Lymphoma

Inclusion Criteria

• Phase 1 Part: Patients with pathologically confirmed advanced stage B-cell NHL (Ann Arbor stage 3 or 4) for whom R-CHOP is considered appropriate therapy; newly diagnosed DLBCL, newly diagnosed low grade B cell NHL, and previously treated low grade B cell NHL patients in first relapse after a prior treatment with non-anthracycline containing chemotherapy are allowed; double hit and transformed diffuse large B cell lymphoma are allowed * Allowed low grade B cell lymphomas will include follicular lymphoma any grade, marginal zone lymphoma including mucosa-associated lymphoid tissue (MALT) lymphoma, indolent mantle cell lymphoma and Waldenstrom's Macroglobulinemia
• Phase 2 Part * DLBCL (Group A): Patients with pathologically confirmed newly diagnosed diffuse large B cell lymphoma (Ann Arbor stage 3 or 4) with no prior therapies; newly diagnosed double hit and transformed diffuse large B cell lymphoma a (excluding Richter’s transformation from CLL) are allowed in this arm * Richter’s transformation from CLL to DLBCL (Group B):Patients with pathologically confirmed newly diagnosed Richter’s transformation from CLL to DLBCL (all stages)
• Patients must have measurable disease, defined as at least one lesion above and below the diaphragm or stage 4 disease that can be accurately measured in at least one dimension; lymph nodes should be considered abnormal if the long axis is > 1.5 cm and extranodal disease if the long axis is > 1.0 cm, regardless of the short axis
• Allowed prior therapy: * Newly diagnosed DLBCL (phase 1 and phase 2 Group A) and low grade B cell lymphoma (phase 1 only): No prior therapy is allowed except steroids equivalent to maximum of prednisone 60 mg once daily for maximum of ten days (or a total of dexamethasone 90 mg) prior to registration * Relapsed/refractory low grade B cell lymphoma (only allowed phase I): A minimum and maximum of one line of prior non-anthracycline containing therapy is allowed; prior localized radiation therapy is not considered a line ** Allowed low grade B cell lymphomas will include follicular lymphoma any grade, marginal zone lymphoma including MALT lymphoma, indolent mantle cell lymphoma and Waldenstrom's Macroglobulinemia * Newly diagnosed Richter’s transformation from CLL to DLBCL (Phase 2 Group B): No prior therapy specific to DLBCL is allowed except steroids equivalent to maximum of prednisone 60 mg once daily for maximum of ten days (or total of dexamethasone 90 mg) prior to registration; prior non-anthracycline based therapy or CLL specific therapies are allowed ** For patients who have had prior chemotherapy or immunotherapy, at least 2 weeks must have elapsed between last dose and initial dose of RCHOP-selinexor; for patients treated with radio-immunotherapy, at least 12 weeks
• All races and ethnic groups are eligible for this trial
• Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 60%)
• Life expectancy of greater than 6 months
• Premenopausal female patients of child-bearing potential must agree to use dual methods of contraception and have a negative serum pregnancy test (serum beta-human chorionic gonadotropin test) at screening, and male patients must use an effective barrier method of contraception if sexually active with a female of child-bearing potential; acceptable methods of contraception are condoms with contraceptive foam, oral, implantable or injectable contraceptives, contraceptive patch, intrauterine device, diaphragm with spermicidal gel, or a sexual partner who is surgically sterilized or post-menopausal; for both male and female patients, effective methods of contraception must be used throughout the study and for three months following the last dose
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• Patients with DLBCL who have received chemotherapy or immunotherapy (except one week of steroids as described above) at any time point in the past for therapy of the DLBCL; patients with low grade B cell lymphomas who have received more than one prior line of chemotherapy or any anthracycline-containing therapy in the past for their low grade B cell lymphoma; localized radiation therapy does not count as a line of therapy
• Patients who are receiving any other investigational agents
• Patients with known brain, spinal or cerebrospinal fluid (CSF) involvement are excluded * Prophylactic intrathecal therapy is allowed per institutional protocol if deemed necessary
• History of severe allergic reactions (as determined by treating physician) attributed to the drugs being used in the study
• Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, congestive heart failure (New York Heart Association [NYHA] class >= 3 or left ventricular ejection fraction < 45%), unstable angina pectoris, myocardial infarction within the last 3 months, clinically significant cardiac arrhythmia (i.e., ventricular tachycardia on anti-arrhythmia are excluded; 1st degree atrioventricular [AV] block or asymptomatic left anterior fascicular block [LAFB]/right bundle branch block [RBBB] permissible), or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant and lactating women are excluded
• Human immunodeficiency virus (HIV)-positive patients regardless of treatment are excluded; patients with evidence of active hepatitis B and hepatitis C infection with positive real time polymerase chain reaction (qPCR) are also excluded but patients with prior exposure to hepatitis B or C with negative qPCR are allowed
• Patients with severe intolerance to glucocorticoids
• Major surgery within 2 weeks of first dose of study drug
• Patients who are unable to swallow tablets, patients with malabsorption syndrome, or any other gastrointestinal (GI) disease or GI dysfunction that could interfere with absorption of study treatment
• Absolute neutrophil count (ANC) < 1500 cells/mm^3 at the time of screening
• Platelet count < 100,000/mm^3 at the time of screening
• Serum bilirubin > 1.5 times the upper limit of normal (ULN) (except patients with Gilbert’s syndrome: total bilirubin of > 3 x ULN) at the time of screening
• Total bilirubin of > 3 x ULN) at the time of screening
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) > 2.5 times ULN at the time of screening
• Estimated creatinine clearance of < 30 mL/min, calculated using the formula of Cockcroft and Gault at the time of screening