Phase I Trial of Selinexor (KPT-330) and Ifosfamide, Carboplatin, Etoposide (ICE) in Peripheral T-cell Lymphoma

Inclusion Criteria:

* Patients must have histologically confirmed T or NK/T-cell lymphomas including the following histologies:

  * Peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS)
  * Angioimmunoblastic T-cell lymphomas (AITL)
  * Anaplastic large cell lymphoma (ALCL)
  * Natural-killer/T-cell lymphoma (NKTL)
* Patients must have received at least two cycles of one prior regimen 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
  * For patients who have CD30+ anaplastic large cell lymphoma, they must have failed or are ineligible or intolerant of brentuximab vedotin
* 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 ≥75,000/mm³
  * Creatinine clearance ≥40ml/min
  * Total bilirubin ≤1.5x ULN. Higher levels are acceptable if these can be attributed to active haemolysis 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 KPT-330 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.

As the effects of selinexor on the developing human fetus at the recommended therapeutic dose are unknown, women of childbearing potential should be advised to avoid becoming pregnant and men should be advised to not father a child while receiving treatment with selinexor. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Women that are pregnant or breastfeeding are excluded from the study because the risks to an unborn fetus or potential risks in nursing infants are unknown.

* 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 who have had prior malignancies (other than T and NK/T-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.
* Patients with known or suspected hypersensitivity to selinexor.

Inclusion of Women and Minorities:

Men and women of all ethnic groups are eligible for this study