This phase I trial studies the best dose and side effects of recombinant vesicular stomatitis virus (VSV) carrying the human (h) sodium iodide symporter (NIS) and Interferon (IFN) beta (β) genes (VSV-hIFNβ-NIS) in combination with cemiplimab in patients with T-cell lymphoma. A virus, called VSV-hIFNβ-NIS, which has been changed in a certain way, may be able to kill cancer cells without damaging normal cells. Immunotherapy with ipilmumab and cemiplimab may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread.

PRIMARY OBJECTIVE: To determine the maximum tolerated dose (MTD) of VSV-hIFNβ-NIS in combination with cemiplimab in patients with T-cell lymphoma [Group E].

Patients undergo computed tomography (CT) scan, position emission tomography (PET) scan throughout the study. Patients may undergo tumor biopsy, bone marrow biopsy and blood sample collection throughout the study.

After completion of study treatment, patients are followed up for 28 days, and then every 3 months for up to 1 year or until progressive disease, then every 6 months for 1 year.

Inclusion Criteria:

• Age >= 18 years

• Relapsed or refractory:

  • Group E only: Relapsed peripheral T-cell lymphoma (PTCL) of the following histologies: peripheral T-cell lymphoma-NOS (PTCL-NOS); anaplastic large cell (ALCL), and mycosis fungoides (MF)

• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2 times upper limit of normal (ULN) (obtained =< 15 days prior to registration)

• Creatinine =< 2.0 mg/dL (obtained =< 15 days prior to registration)

• Direct bilirubin =< 1.5 x ULN (obtained =< 15 days prior to registration)

• International normalized ratio (INR)/prothrombin time (PT) and activated partial thromboplastin time (aPTT) =< 1.5 x ULN (obtained =< 15 days prior to registration)

• If baseline liver disease, Child Pugh score not exceeding class A (obtained =< 15 days prior to registration)

• Negative pregnancy test for persons of child-bearing potential (obtained =< 15 days prior to registration)

• FOR T-Cell Lymphoma (TCL)/B-Cell Lymphoma (BCL) ONLY: Absolute Neutrophil Count (ANC) >= 1,000/microliter (μL) (obtained =< 14 days prior to registration)

• FOR TCL/BCL ONLY: Platelets >= 100,000/μL (obtained =< 14 days prior to registration)

• FOR TCL/BCL ONLY: Hemoglobin >= 8.5 g/dl (obtained =< 14 days prior to registration)

• FOR TCL/BCL ONLY: Measurable disease by CT or magnetic resonance imaging (MRI): must have at least one lesion that has a single diameter of > 2 cm or tumor cells in the blood > 5 x 10^9/L; NOTE: skin lesions can be used if the area is > 2 cm in at least one diameter and photographed with a ruler and the images are available in the medical record

• Absence of active central nervous system (CNS) involvement; NOTE: pre-enrollment lumbar puncture not mandatory

• Ability to provide written informed consent

• Willingness to return to Mayo Clinic for follow-up

• Life expectancy >= 12 weeks

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

• Willing to provide mandatory biological specimens for research purposes

Exclusion Criteria:

• Availability of and patient acceptance of curative therapy

• Uncontrolled infection

• Active tuberculosis or hepatitis, or chronic hepatitis

• Any of the following prior therapies:

  • Chemotherapy (IMIDs, alkylating agents, proteosome inhibitors) =< 2 weeks prior to registration
  • Immunotherapy (monoclonal antibodies) =< 4 weeks prior to registration
  • Experimental agent in case of Acute Myeloid Leukemia (AML) or TCL within 4 half-lives of the last dose of the agent

• New York Heart Association classification III or IV, known symptomatic coronary artery disease, or symptoms of coronary artery disease on systems review, or known cardiac arrhythmias [atrial fibrillation or supraventricular tachycardia (SVT)]

• Active CNS disorder or seizure disorder or known CNS disease or neurologic symptomatology; in case of AML active CNS involvement as detected by lumbar puncture or neuro-imaging (only to be done if clinically indicated)

• Human immunodeficiency virus (HIV) positive test result or other immunodeficiency or immunosuppression

• Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (used for a non-Food and Drug Administration [FDA] approved indication and in the context of a research investigation);

  • NOTE: in TCL, patients may use topical emollients or corticosteroids, acetic acid soaks, etc. to control pruritus and prevent infection; no topical chemotherapy is allowed (no topical nitrogen mustard)

• 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 or women of reproductive ability who are unwilling to use effective contraception
  • Nursing women
  • Men who are unwilling to use a condom (even if they have undergone a prior vasectomy) while having intercourse with any woman, while taking the drug and for 4 weeks after stopping treatment

• ADDITIONAL EXCLUSION CRITERIA FOR GROUP E (COMBINATION WITH CEMIPLIMAB) ONLY:

  • Diagnosis of AML
  • Diagnosis of Angioimmunoblastic T-cell Lymphoma (AITL)