Romidepsin and Lenalidomide in Treating Patients With Previously Untreated Peripheral T-Cell Lymphoma

Histologically confirmed diagnosis of PTCL (using the most recent edition of the World Health Organization \[WHO\] Classification of Tumors of Hematopoietic and Lymphoid Tissues as guidance) including:

* Anaplastic large cell lymphoma, anaplastic large cell kinase (ALK)-negative

* Angioimmunoblastic T-cell lymphoma

* Enteropathy-type T-cell lymphoma

* Extranodal natural killer (NK)/T-cell lymphoma, nasal type

* Hepatosplenic gamma-delta T-cell lymphoma

* Peripheral T-cell lymphoma, unspecified (not otherwise specified \[NOS\])

* Transformed mycosis fungoides

* Subcutaneous panniculitis-like T-cell lymphoma.

* NOTE: Patients with adequate archived (well-preserved, formalin-fixed) biopsy tissue remaining will be required to submit a portion for exploratory studies; this is not optional if tissue is available; however, lack of adequate tissue for exploratory studies will not preclude patients from participating

Patients must have bi-dimensionally measurable disease (\>= 1 cm) by CT imaging

* NOTE: Patients with marrow-only disease are eligible; response for these patients will be assessed by repeat bone marrow biopsy

Patients must fit into one of the following categories:

* Age \>= 18 years to \< 60 years with a cumulative illness rating scale (CIRS) score \>= 6 OR deemed ineligible for cytotoxic chemotherapy by the treating investigator

* \>= 60 years

Patients must have adequate organ and marrow function (documented within 14 days prior to registration) as outlined below:

* Absolute neutrophil count (ANC) \>= 750/mcl

* Hemoglobin \>= 8 g/dl

* Platelets \>= 50,000/mcl

* Total bilirubin =\< 2 x upper limit normal (ULN)

* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum pyruvate glutamate transaminase \[SPGT\]) =\< 3 x ULN

* Creatinine =\< 2 x ULN

Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status =\< 2

All patients must agree to use effective contraception while on study, and all patients must agree to undergo counseling sessions every 28 days about pregnancy precautions and risks of fetal exposure

* Females of childbearing potential (FCBP) must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control: one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before starting lenalidomide, during lenalidomide therapy, during dose interruptions, and for at least 28 days following discontinuation of lenalidomide therapy

* Males receiving lenalidomide must agree to use a latex condom during any sexual contact with FCBPs even if they have undergone a successful vasectomy

* NOTE: A FCBP is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

* Has not undergone a hysterectomy or bilateral oophorectomy

* Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)

* FCBP should be referred to a qualified provider of contraceptive methods, if needed

FCPB must have a negative urine or serum pregnancy test within 7 days prior to registration, and be willing to adhere to the scheduled pregnancy testing as required in the Revlimid Risk Evaluation and Mitigation Strategies (REMS®) program

* NOTE: Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately

Patients must be free of any prior malignancies for \>= 1 year

* NOTE: The exception to this would be currently treated squamous cell and basal cell carcinoma of the skin, carcinoma in situ of the cervix, breast, or bladder, or surgically removed melanoma in situ of the skin (stage 0) with histologically confirmed free margins of excision

All study participants must be registered into the mandatory Revlimid REMS® program, and be willing and able to comply with the requirements of the REMS® program

Patients must have the ability to understand and the willingness to sign a written informed consent prior to registration

What this study is about