Extracorporeal Photopheresis and Mogamulizumab for the Treatment of Erythrodermic Cutaneous T Cell Lymphoma

• 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)

Exclusion Criteria:

• Prior mogamulizumab
• Any systemic therapy, including monoclonal antibody within 28 days or 5 half-lives (whichever is shorter) of initiating protocol therapy
• Chemotherapy, radiation therapy, biological therapy, immunotherapy within 21 days prior to day 1 of protocol therapy
• Any skin-directed therapy within 14 days prior to initiating protocol therapy
• Any radiation therapy within 21 days prior to initiating protocol therapy

• Immunosuppressive medication within 14 days prior to the first dose of study treatment. The following are exceptions to this criterion:

  • Intranasal, inhaled, topical or local steroid injections (e.g., intra-articular injection) and are on stable dose for at least 28 days
  • Systemic corticosteroids at physiologic doses of \< 10 mg/day of prednisone or equivalent
• Live, attenuated vaccine within 30 days prior to the first dose protocol therapy

• Disease free of prior malignancies for >= 5 years with the exception of:

  • Currently treated squamous cell and basal cell carcinoma of the skin, or
  • Carcinoma in situ of the cervix, or
  • Surgically removed melanoma in situ of the skin (stage 0) with histological confirmed free margins of excision, or
  • Prostate cancer (T1a or T1b using the TNM [tumor, nodes, metastasis] clinical staging system) that has/have been surgically cured, or
  • Any other malignancy that has/have been curatively treated with surgery and/or localized radiation
• Active infection requiring antibiotics
• Known hepatitis B or hepatitis C infection
• Other active malignancy
• Females only: Pregnant or breastfeeding
• Prior stem cell transplantation
• Acute infection requiring systemic treatment
• Conditions requiring chronic steroid or immunosuppressive treatment that likely need additional steroid or immunosuppressive treatments in addition to the protocol therapy
• Renal failure requiring hemodialysis or peritoneal dialysis

• Unstable cardiac disease as defined by one of the following:

  • Cardiac events such as myocardial infarction (MI) within the past 6 months
  • NYHA (New York Heart Association) heart failure class III-IV
  • Uncontrolled atrial fibrillation or hypertension
• Major surgery (as defined by the investigator) within the 28 days prior to the first dose of study treatment

• Active or prior documented autoimmune or inflammatory disorders requiring therapy within the past 3 years prior to the start of treatment. The following are exceptions to this criterion:

  • Vitiligo or alopecia
  • Hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement; or
  • Psoriasis not requiring systemic treatment
• History of primary immunodeficiency
• Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures.
• Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)