Inclusion Criteria:
- - Non Hodgkin or Hodgkin lymphoma or histiocytic/dendritic cell neoplasm meeting one of
the following criteria:
- Biopsy-proven relapsed and/or refractory Non-Hodgkin or Hodgkin lymphoma or
histiocytic/dendritic cell neoplasms.
- - Relapsed is defined as a relapse that occurred after having a response to
the last therapy that lasted > 26 weeks.
- - Refractory is no response (stable disease or progressive disease while on
therapy) or relapse within 6 months.
Refractoriness to autologous stem cell
transplant will be defined as disease progression within 52 weeks following
transplant OR. Multiple myeloma neoplasm meeting the following criteria:
- - Relapsed and/or refractory multiple myeloma (RRMM) as per the International Myeloma
Working Group (IMWG) uniform criteria.
- - If extramedullary myeloma, most recent tumor biopsy must be < 26 weeks prior to
registration.
- - 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) or
MRI: To be considered measurable, there must be at least one lesion that has a
single 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 with
assessable disease by PET/CT are also eligible as long as the assessable disease
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 is
abnormal.
- - Measurable plasmacytoma (at least one lesion that has a single diameter of >= 2
cm on CT portion of PET/CT scan or MRI)
- Bone marrow plasma cells >= 10%
- Exception: A patient with non-secretory multiple myeloma (MM) but with bone
marrow plasma cells >= 30% may be considered for enrollment after discussion
with the PI that includes the feasibility of an individualized plan for
response assessment.
- - Patients with Immunoglobulin A (IgA) or Immunoglobulin D (IgD) myeloma in whom
serum protein electrophoresis is deemed unreliable, due to co-migration of normal
serum proteins with the para protein in the beta region, may be considered
eligible as long as total serum IgA or IgD level is elevated above normal range.
- - Patients with non-Hodgkin or Hodgkin lymphoma must have previously been
treated with >= 2 lines of therapy.
- - Patients with histiocytic/dendritic cell neoplasms must previously have been
treated with >= 1 line of therapy.
- - Patients with RRMM must have received ≥4 prior therapies whose disease is
refractory 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 prior to
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 with well-documented
Gilbert's syndrome) (obtained =< 14 days prior to registration)
- 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 Cockcroft
Gault formula (obtained =< 14 days prior to registration)
- Negative pregnancy test done =< 7 days prior to registration, for women of
childbearing potential only.
- - Female of childbearing potential (FCBP*) must commit to take highly
effective contraceptive precautions** without interruption during the study
and continue for at least 12 weeks after the last dose of selinexor and CS.
FCBP must refrain from breastfeeding and donating oocytes during the course
of the study. Males must use an effective barrier method of contraception
without interruption during the study and continue for at least 12 weeks
after the last dose of selinexor and CS. They must refrain from donating
sperm during the study participation.
- - *FCBP defined as sexually mature women who have not undergone bilateral tubal
ligation, bilateral oophorectomy, or hysterectomy; or who have not been postmenopausal
(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 rate
of less than 1% per year when used consistently and correctly.
Highly effective
forms of birth control include: hormonal contraceptives (oral, injectable, patch,
and intrauterine devices), male partner sterilization, or total abstinence from
heterosexual intercourse, when this is the preferred and usual lifestyle of the
patient NOTE: The double-barrier method (e.g., synthetic condoms, diaphragm, or
cervical cap with spermicidal foam, cream, or gel), periodic abstinence (such as
calendar, symptothermal, post-ovulation), withdrawal (coitus interruptus),
lactational amenorrhea method, and spermicide-only are not acceptable as highly
effective methods of contraception.
- - Provide written informed consent.
- - Willing to return to enrolling institution for follow-up (during the Active
Monitoring Phase of the study)
- Willingness to provide mandatory blood specimens per protocol for
Pharmacokinetics (PKs) and banking.
- - For lymphoma, extramedullary myeloma and histiocytic/dendritic cell
neoplasms, willing to provide mandatory tissue samples for correlative
research.
NOTE: If an institution is not able to provide the tissue, it does
not cause the patient to be ineligible; however, the collection of these
tissues is strongly recommended.
Exclusion Criteria:
- - Any of the following because this study involves an investigational agent whose
genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are
unknown:
- Pregnant women.
- - Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment
of the investigator, would make the patient inappropriate for entry into this study or
interfere significantly with the proper assessment of safety and toxicity of the
prescribed regimens.
- - Patients known to have active hepatitis B, or C infection, or known to be positive for
hepatitis C virus (HCV) ribonucleic acid (RNA) or hepatitis B surface antigen (HBsAg)
(hepatitis B virus [HBV] surface antigen).
Patients known to be human immunodeficiency
virus (HIV) positive, except those with CD4+ T-cell (CD4+) counts >= 350 cells/uL and
on an established antiretroviral therapy (ART) for at least twelve weeks and have an
HIV viral load less than 400 copies/mL prior to enrollment.
- - Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.
- - Life expectancy of < 6 months.
- - Active gastrointestinal (GI) dysfunction interfering with the ability to swallow
tablets, or any GI dysfunction that could interfere with absorption of study treatment.
- - Known intolerance to or contraindications for choline salicylate therapy.
Patients
with 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 treatment for
the primary neoplasm.
- - Active second malignancy requiring treatment that would interfere with the assessment
of the response of the primary cancer to this protocol therapy.
Patients with treated
malignancies on hormonal therapy (for example breast or prostate cancer) are eligible.
- - History of myocardial infarction =< 6 months, or congestive heart failure requiring
use of ongoing maintenance therapy for life-threatening ventricular arrhythmias.
- - Radiation, chemotherapy, or immunotherapy or any other anticancer therapy =< 2 weeks
prior to registration.
NOTE: Exception: patients on any BTK inhibitor (ibrutinib,
zanabrutinib, acalabrutinib, etc), or venetoclax, or corticosteroids (any dose) may
continue therapy up until the new regimen has started at investigator discretion.
After the start of protocol therapy, corticosteroids can be 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 autologous stem
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 CNS
involvement 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 disease
can enroll, but the ASA needs to be held while on this protocol therapy
