KPT-330 Plus RICE for Relapsed/Refractory Aggressive B-Cell Lymphoma

Inclusion Criteria:

* Patients must have histologically confirmed aggressive B-cell non-Hodgkin lymphomas:

  * DLBCL including ABC, GCB or PMBCL subtypes
  * Double/triple hit lymphomas
  * Indolent lymphomas transformed to aggressive lymphomas
  * Follicular lymphomas grade 3B
* Patients must have received at least two cycles of anthracycline based chemotherapy administered with curative intent and one of the following:

  * failed to have achieve at least a partial response after 2 or more cycles
  * failed to achieve a complete response after 6 or more cycles
  * progressed after an initial response
* Patients must be age ≥18 years.
* Patients must have at least one site of measurable disease, 1.5 cm in diameter or greater.
* Patients must have ECOG performance status of 0-2.
* Patients must have laboratory test results within these ranges:

  * Absolute neutrophil count ≥ 1500/mm³
  * Platelet count ≥ 100,000/mm³
  * Serum creatinine clearance ≥40 mL/min
  * Total bilirubin ≤ 1.5x ULN. Higher levels are acceptable if these can be attributed to active hemolysis or ineffective erythropoiesis.
  * AST (SGOT) and ALT (SGPT) ≤ 2x ULN
* Women of childbearing potential must agree to use dual methods of contraception and have a negative serum pregnancy test prior to selinexor treatment. 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.
* Patients must be able to understand and willing to sign a written informed consent document.
* Patients must be able to adhere to the study visit schedule and other protocol requirements.
* Patients must not have any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
* Patients must not have any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.

Exclusion Criteria:

* Patients with hyperuricemia or other potential signs of tumor lysis syndrome
* Patients with more than minimally symptomatic disease (i.e. \> grade 1), high tumor burden, or other indication for urgent treatment.
* Patients who have had prior malignancies (other than B-cell lymphomas) for ≤5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast.
* Patients who have had other anti-cancer therapy, including radiation or experimental drug or therapy, within 28 days of enrollment.
* Patients with known HIV, active hepatitis B, active hepatitis C.
* Patients with known central nervous system involvement by lymphoma.