Brentuximab Vedotin and Lenalidomide in Treating Patients With Stage IB-IVB Relapsed or Refractory T-Cell Lymphoma

Able to understand and voluntarily sign an informed consent form

Able to adhere to the study visit schedule and other protocol requirements

Biopsy-proven, measurable, stage IB-IVB relapsed or refractory cutaneous T-cell lymphoma after 2 lines of skin-directed therapy or one prior line of systemic therapy

* (Note: extracorporeal photopheresis will be considered a systemic therapy for this study)

Patients with large cell transformation of cutaneous T cell lymphoma are eligible

Patients with advanced stage non-mycosis fungoides (MF) CTCL are eligible including, but not limited to, advanced stage lymphomatoid papulosis (LyP) or primary cutaneous anaplastic large cell lymphoma (pcALCL)

Patients with systemic T cell lymphoma of any stage and any subtypes; patient must have had at least one standard chemotherapy and measurable disease at the time of enrollment; bidimensional measurable disease of at least 1.5 cm in the greatest transverse diameter as documented by computed tomography (CT) or positron emission tomography (PET)/CT

Patients with systemic T cell lymphomas who relapsed after autologous transplant are eligible

Prior treatment with brentuximab vedotin is allowed provided the patient did not progress on BV or within 30 days of last dose of BV; patients must be at least 3 months from the last dose of BV

CD30 staining is to be performed on fresh biopsy or archival formalin-fixed paraffin-embedded (FFPE) tissue however CD30 positivity is not required for eligibility

All cancer therapy, including radiation, topical steroid, and chemotherapy must have been discontinued at least 1 week or 3 half-lives whichever is the longest prior to treatment in this study; the only exceptions are participants who are symptomatic from their skin lesions and have been on corticosteroids for prolonged periods of time (\> 60 days) without change may continue use of either systemic steroids (equivalent to \< 10 mg per day of prednisone) or topical steroids are eligible for this study if the frequency and dosage steroids has not changed for 60 days prior to the study; these participants should continue on the same dose of systemic/topical steroid throughout the study period unless they achieve a complete response at which time steroids can be discontinued; patients are allowed to continue any medications with known activity in T cell lymphomas at the pre-enrollment doses for conditions other than T cell lymphomas (ie, steroids for sarcoidosis), as long as there is evidence of T cell lymphoma progression while patients were on these agents

Eastern Cooperative Oncology Group (ECOG) performance status of =\< 2 at study entry

Absolute neutrophil count \>= 1000/mm\^3

Platelet count \>= 50,000/mm\^3

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

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

AST (SGOT) and ALT (SGPT) =\< 5 x ULN in patients with documented hepatic involvement by lymphoma

Calculated creatinine clearance \>= 60 ml/min (by the Cockcroft-Gault equation)

Disease free of prior malignancies 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 with early stage of prostate cancer under clinical surveillance without therapy are eligible

Negative serum pregnancy test at the time of enrollment for females of childbearing potential

Women of childbearing potential must follow pregnancy testing requirements as outlined in the Revlimid Risk Evaluation and Mitigation Strategy (REMS) program material; this is defined as either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of contraception (one highly effective method and one additional effective method (AT THE SAME TIME) at least 28 days prior to the start of lenalidomide, for the duration of study participation, and for 28 days following the last doses of brentuximab vedotin and lenalidomide; women of childbearing potential must also agree to ongoing pregnancy testing; men must agree to use a latex condom during sexual contact with a woman of childbearing potential even if they have had a successful vasectomy; all patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure; should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately

All study participants must be registered into the mandatory Revlimid REMS program and be willing to comply with its requirements; per standard Revlimid REMS program requirements, all physicians who prescribe lenalidomide for research subjects enrolled into this trial, must be registered in, and must comply with, all requirements of the Revlimid REMS program

Life expectancy \> 30 days

Any illness, medical condition or organ system dysfunction which, in the investigator?s opinion, could compromise the subject?s safety, interfere with the absorption or metabolism of lenalidomide, or put the study outcomes at undue risk

A cardiovascular disability status of New York Heart Association class \>= 2

History of severe allergic reactions to humanized monoclonal antibodies

History of other malignancy that could affect compliance with the protocol or interpretation of results; patients with a history of curatively treated basal or squamous cell carcinoma or stage 1 melanoma of the skin or in situ carcinoma of the cervix are eligible; individuals in documented remission without treatment for 2 years prior to enrollment may be included at the discretion of the investigator; patients with early stage of prostate cancer under clinical surveillance without therapy are eligible

Known hypersensitivity to any of the study drugs or analogs

Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment, or any major episode of infection requiring treatment with IV antibiotics or hospitalization (relating to the completion of the course of antibiotics) within 4 weeks prior study therapy

Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis

Receipt of live-virus vaccines within 28 days prior to the initiation of study treatment or need for live-virus vaccines at any time during study treatment

Recent major surgery (within 6 weeks prior to the start of study treatment) other than for diagnosis

Receiving immunosuppressive therapy

Refractory to prior therapy with brentuximab vedotin (evidence of progression within 30 days of the last dose)

Prior therapy with lenalidomide

Pregnant or lactating, or intending to become pregnant during the study

What this study is about