Low-Dose Selinexor and Choline Salicylate for Non-Hodgkin or Hodgkin Lymphoma, Histiocytic/Dendritic Cell Neoplasm, or Relapsed or Refractory Multiple Myeloma

Inclusion Criteria:

• Age >= 18 years

• Non Hodgkin or Hodgkin lymphoma or histiocytic/dendritic cell neoplasm meeting oneof the following criteria:

• Biopsy-proven relapsed and/or refractory Non-Hodgkin or Hodgkin lymphoma orhistiocytic/dendritic cell neoplasms

• Relapsed is defined as a relapse that occurred after having a response tothe last therapy that lasted > 26 weeks

• Refractory is no response (stable disease or progressive disease while ontherapy) or relapse within 6 months. Refractoriness to autologous stemcell transplant will be defined as disease progression within 52 weeksfollowing transplant OR

Multiple myeloma neoplasm meeting the following criteria:

• Relapsed and/or refractory multiple myeloma (RRMM) as per the International MyelomaWorking Group (IMWG) uniform criteria

• If extramedullary myeloma, most recent tumor biopsy must be < 26 weeks prior toregistration

• Measurable or assessable disease:

• For Non-Hodgkin or Hodgkin Lymphoma and histiocytic/dendritic cell:

• Measurable disease is defined as measurable by computed tomography (CT) [dedicated CT or the CT portion of a positron emission tomography (PET)/CT] orMRI: To be considered measurable, there must be at least one lesion that has asingle diameter of >= 1.5 cm NOTE: Skin lesions can be used if the area is >= 1.5 cm in at least one diameter and photographed with a ruler. Patients withassessable disease by PET/CT are also eligible as long as the assessabledisease is biopsy proven lymphoma or histiocytic/dendritic cell neoplasms

• For Multiple myeloma:

• Measurable disease by IMWG criteria as defined by at least one of the following:

• Serum M-protein >= 0.5 g/dL

• Urine M-protein >= 200 mg in a 24-hour collection

• Serum Free Light Chain level >= 10 mg/dL provided the free light chain ratio isabnormal

• Measurable plasmacytoma (at least one lesion that has a single diameter of >= 2cm on CT portion of PET/CT scan or MRI)

• Bone marrow plasma cells >= 10%

• Exception: A patient with non-secretory multiple myeloma (MM) but withbone marrow plasma cells >= 30% may be considered for enrollment afterdiscussion with the PI that includes the feasibility of an individualizedplan for response assessment

• Patients with Immunoglobulin A (IgA) or Immunoglobulin D (IgD) myeloma in whomserum protein electrophoresis is deemed unreliable, due to co-migration ofnormal serum proteins with the para protein in the beta region, may beconsidered eligible as long as total serum IgA or IgD level is elevated abovenormal range

• Patients with non-Hodgkin or Hodgkin lymphoma must have previously beentreated with >= 2 lines of therapy

• Patients with histiocytic/dendritic cell neoplasms must previously havebeen treated with >= 1 line of therapy

• Patients with RRMM must have received ≥4 prior therapies whose disease isrefractory to >= 2 proteasome inhibitors, >= 2 immunomodulatory agents,and an anti-CD38 monoclonal antibody

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1,or 2

• Absolute neutrophil count (ANC) >= 1,000/mm^3 (obtained =< 14 days priorto registration)

• Platelet count >= 100,000/mm^3 (obtained =< 14 days prior to registration)

• Hemoglobin >= 8.5 g/dL (may be transfused to reach criteria) (obtained =< 14 days prior to registration)

• Total bilirubin < 2 x upper limit of normal (ULN) (or total bilirubin =< 3.0 x ULN with direct bilirubin =< 1.5 x ULN in patients withwell-documented Gilbert's syndrome) (obtained =< 14 days prior toregistration)

• Aspartate transaminase (AST) =< 2.5 x ULN and alanine aminotransferase (ALT) =< 2.5 x ULN (obtained =< 14 days prior to registration)

• Calculated creatinine clearance must be >= 35 ml/min using the CockcroftGault formula (obtained =< 14 days prior to registration)

• Negative pregnancy test done =< 7 days prior to registration, for women ofchildbearing potential only

• Female of childbearing potential (FCBP*) must commit to take highlyeffective contraceptive precautions** without interruption during thestudy and continue for at least 12 weeks after the last dose of selinexorand CS. FCBP must refrain from breastfeeding and donating oocytes duringthe course of the study. Males must use an effective barrier method ofcontraception without interruption during the study and continue for atleast 12 weeks after the last dose of selinexor and CS. They must refrainfrom donating sperm during the study participation.

• *FCBP defined as sexually mature women who have not undergone bilateral tuballigation, bilateral oophorectomy, or hysterectomy; or who have not beenpostmenopausal (i.e., who have not menstruated at all) for at least 1 year

• Highly effective forms of birth control are methods that achieve a failure rateof less than 1% per year when used consistently and correctly. Highly effectiveforms of birth control include: hormonal contraceptives (oral, injectable,patch, and intrauterine devices), male partner sterilization, or totalabstinence from heterosexual intercourse, when this is the preferred and usuallifestyle of the patient NOTE: The double-barrier method (e.g., syntheticcondoms, diaphragm, or cervical cap with spermicidal foam, cream, or gel),periodic abstinence (such as calendar, symptothermal, post-ovulation),withdrawal (coitus interruptus), lactational amenorrhea method, andspermicide-only are not acceptable as highly effective methods of contraception

• Provide written informed consent

• Willing to return to enrolling institution for follow-up (during theActive Monitoring Phase of the study)

• Willingness to provide mandatory blood specimens per protocol forPharmacokinetics (PKs) and banking

• For lymphoma, extramedullary myeloma and histiocytic/dendritic cellneoplasms, willing to provide mandatory tissue samples for correlativeresearch. NOTE: If an institution is not able to provide the tissue, itdoes not cause the patient to be ineligible; however, the collection ofthese tissues is strongly recommended.

Exclusion Criteria:

• Any of the following because this study involves an investigational agent whosegenotoxic, mutagenic and teratogenic effects on the developing fetus and newborn areunknown:

• Pregnant women

• Nursing women

• Co-morbid systemic illnesses or other severe concurrent disease which, in thejudgment of the investigator, would make the patient inappropriate for entry intothis study or interfere significantly with the proper assessment of safety andtoxicity of the prescribed regimens

• Patients known to have active hepatitis B, or C infection, or known to be positivefor hepatitis C virus (HCV) ribonucleic acid (RNA) or hepatitis B surface antigen (HBsAg) [hepatitis B virus (HBV) surface antigen]. Patients known to be humanimmunodeficiency virus (HIV) positive, except those with CD4+ T-cell (CD4+) counts >= 350 cells/microliter (µL) and on an established antiretroviral therapy (ART) forat least twelve weeks and have an HIV viral load less than 400 copies/mL prior toenrollment

• Uncontrolled intercurrent illness including, but not limited to, ongoing or activeinfection, symptomatic congestive heart failure, unstable angina pectoris, cardiacarrhythmia, or psychiatric illness/social situations that would limit compliancewith study requirements

• Life expectancy of < 6 months

• Active gastrointestinal (GI) dysfunction interfering with the ability to swallowtablets, or any GI dysfunction that could interfere with absorption of studytreatment

• Known intolerance to or contraindications for choline salicylate therapy. Patientswith known allergy to acetylsalicylic acid (ASA) are not eligible

• Prior exposure to a selective inhibitors of nuclear export (SINE) compound,including selinexor

• Receiving any other investigational agent which would be considered as a treatmentfor the primary neoplasm

• Active second malignancy requiring treatment that would interfere with theassessment of the response of the primary cancer to this protocol therapy. Patientswith treated malignancies on hormonal therapy (for example breast or prostatecancer) are eligible

• History of myocardial infarction =< 6 months, or congestive heart failure requiringuse of ongoing maintenance therapy for life-threatening ventricular arrhythmias

• Radiation, chemotherapy, or immunotherapy or any other anticancer therapy =< 2 weeksprior to registration. NOTE: Exception: patients on any Bruton tyrosine kinase (BTK)inhibitor (ibrutinib, zanabrutinib, acalabrutinib, etc), or venetoclax, orcorticosteroids (any dose) may continue therapy up until the new regimen has startedat investigator discretion. After the start of protocol therapy, corticosteroids canbe used at investigator's discretion and tapered to lowest possible dose

• Active graft versus (vs.) host disease (after allogeneic stem cell transplantation)at registration

• Major surgery (including bowel resection) =< 3 weeks prior to registration

• Must not be currently eligible or have declined high-dose therapy with autologousstem cell transplantation rescue or chimeric antigen receptor (CAR)-T cell therapy

• Primary mediastinal (thymic) large B-cell lymphoma (PMBL)

• Known active central nervous system (CNS) lymphoma. Patients with previous CNSinvolvement can enroll if the CNS component is inactive

• Patients who are on active anticoagulant therapy with direct oral anticoagulants (DOACs), aspirin or warfarin are not eligible due to potential bleeding. EXCEPTIONS:Patients who are on aspirin (81 mg) for primary prevention of cardiovascular diseasecan enroll, but the ASA needs to be held while on this protocol therapy