• Documented informed consent of the participant and/or legally authorized representative

‣ Assent, when appropriate, will be obtained per institutional guideline

• Agreement to allow the use of archival tissue from diagnostic tumor biopsies

‣ If unavailable, exceptions may be granted with study principal investigator (PI) approval

• Age: \>= 18 years

• Eastern Cooperative Oncology Group (ECOG) =\< 2

• Histologically confirmed mycosis fungoides (MF) or Sezary syndrome (SS). Safety lead-in: \>= stage IIB OR \>= stage IB-IIA folliculotropic/transformed MF. Phase 2: \>= stage IB

‣ Stage of disease according to Tumor-Node-Metastasis-Blood (TNMB) classification

⁃ Pathology report must be diagnostic or be consistent with MF/SS criteria

⁃ SS is defined as meeting T4 plus B2 criteria; where the biopsy of erythrodermic skin may only reveal suggestive but not diagnostic histopathologic features, the diagnosis may be based on either node biopsy or fulfillment of B2 criteria

⁃ For MF where the histological diagnosis by light microscopic examination is not confirmed, diagnostic criteria that been recommended by the International Society of Cutaneous Lymphomas (ISCL) should be used.

• Measurable disease per Modified Severity Weighted Assessment Tool (mSWAT) and/or Sezary count

• Baseline skin biopsy taken within 6 months available for central review submission

• Without bone marrow involvement: Absolute neutrophil count (ANC) \>= 1,500/mm\^3 (performed within 7 days prior to day 1 of protocol therapy unless otherwise stated)

‣ NOTE: Growth factor is not permitted within 14 days of ANC assessment unless cytopenia is secondary to disease involvement

• With bone marrow involvement: ANC \>= 1,000/mm\^3 (performed within 7 days prior to day 1 of protocol therapy unless otherwise stated)

‣ NOTE: Growth factor is not permitted within 14 days of ANC assessment unless cytopenia is secondary to disease involvement

• Without bone marrow involvement: Platelets \>= 100,000/mm\^3 (performed within 7 days prior to day 1 of protocol therapy unless otherwise stated)

‣ NOTE: Platelet transfusions are not permitted within 14 days of platelet assessment unless cytopenia is secondary to disease involvement

• With bone marrow involvement: Platelets \>= 75,000/mm3 (performed within 7 days prior to day 1 of protocol therapy unless otherwise stated)

‣ NOTE: Platelet transfusions are not permitted within 14 days of platelet assessment unless cytopenia is secondary to disease involvement

• Total bilirubin =\< 1.5 x upper limit of normal (ULN) (unless has Gilbert's disease)(performed within 7 days prior to day 1 of protocol therapy unless otherwise stated)

• Aspartate aminotransferase (AST) =\< 2.5 x ULN (unless has Gilbert's disease)(performed within 7 days prior to day 1 of protocol therapy unless otherwise stated)

• Alanine aminotransferase (ALT) =\< 2.5 x ULN (unless has Gilbert's disease)(performed within 7 days prior to day 1 of protocol therapy unless otherwise stated)

• Creatinine clearance of \>= 60 mL/min per 24 hour urine test or the Cockcroft-Gault formula (unless has Gilbert's disease) (performed within 7 days prior to day 1 of protocol therapy unless otherwise stated)

• If not receiving anticoagulants: International normalized ratio (INR) OR prothrombin (PT) =\< 1.5 x ULN (performed within 7 days prior to day 1 of protocol therapy unless otherwise stated)

• If on anticoagulant therapy: PT must be within therapeutic range of intended use of anticoagulants (performed within 7 days prior to day 1 of protocol therapy unless otherwise stated)

• If not receiving anticoagulants: Activated partial thromboplastin time (aPTT) =\< 1.5 x ULN (performed within 7 days prior to day 1 of protocol therapy unless otherwise stated)

• If on anticoagulant therapy: aPTT must be within therapeutic range of intended use of anticoagulants (performed within 7 days prior to day 1 of protocol therapy unless otherwise stated)

• Hepatitis C virus (HCV)\*, active hepatitis B virus (HBV) (surface antigen negative), and syphilis (rapid plasma reagin \[RPR\])

‣ If positive, hepatitis C ribonucleic acid (RNA) quantitation must be performed

• Meets other institutional and federal requirements for infectious disease titer requirements

‣ Note Infectious disease testing to be performed within 28 days prior to day 1 of protocol therapy

• Subjects with MF and a history of staphylococcus colonization are eligible provided they continue to receive stable doses of prophylactic antibiotics

• Women of childbearing potential (WOCBP): negative urine or serum pregnancy test If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required

• Agreement by females and males of childbearing potential\* to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 3 months after the last dose of protocol therapy

‣ Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only)