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

Inclusion Criteria:

• Documented informed consent of the participant and/or legally authorizedrepresentative

• 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). Safetylead-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 erythrodermicskin 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 notconfirmed, diagnostic criteria that been recommended by the InternationalSociety of Cutaneous Lymphomas (ISCL) should be used.

• Measurable disease per Modified Severity Weighted Assessment Tool (mSWAT) and/orSezary 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 unlesscytopenia is secondary to disease involvement

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

• NOTE: Growth factor is not permitted within 14 days of ANC assessment unlesscytopenia is secondary to disease involvement

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

• NOTE: Platelet transfusions are not permitted within 14 days of plateletassessment unless cytopenia is secondary to disease involvement

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

• NOTE: Platelet transfusions are not permitted within 14 days of plateletassessment unless cytopenia is secondary to disease involvement

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

• Aspartate aminotransferase (AST) =< 2.5 x ULN (unless has Gilbert'sdisease)(performed within 7 days prior to day 1 of protocol therapy unless otherwisestated)

• Alanine aminotransferase (ALT) =< 2.5 x ULN (unless has Gilbert's disease)(performedwithin 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-Gaultformula (unless has Gilbert's disease) (performed within 7 days prior to day 1 ofprotocol 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 unlessotherwise stated)

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

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

• If on anticoagulant therapy: aPTT must be within therapeutic range of intended useof anticoagulants (performed within 7 days prior to day 1 of protocol therapy unlessotherwise 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 titerrequirements

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

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

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

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

• Childbearing potential defined as not being surgically sterilized (men andwomen) 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 daysprior 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 studytreatment. The following are exceptions to this criterion:

• Intranasal, inhaled, topical or local steroid injections (e.g., intra-articularinjection) and are on stable dose for at least 28 days

• Systemic corticosteroids at physiologic doses of < 10 mg/day of prednisone orequivalent

• 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 histologicalconfirmed free margins of excision, or

• Prostate cancer (T1a or T1b using the TNM [tumor, nodes, metastasis] clinicalstaging system) that has/have been surgically cured, or

• Any other malignancy that has/have been curatively treated with surgery and/orlocalized 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 needadditional steroid or immunosuppressive treatments in addition to the protocoltherapy

• 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 firstdose of study treatment

• Active or prior documented autoimmune or inflammatory disorders requiring therapywithin the past 3 years prior to the start of treatment. The following areexceptions to this criterion:

• Vitiligo or alopecia

• Hypothyroidism (e.g., following Hashimoto syndrome) stable on hormonereplacement; or

• Psoriasis not requiring systemic treatment

• History of primary immunodeficiency

• Any other condition that would, in the Investigator's judgment, contraindicate thepatient's participation in the clinical study due to safety concerns with clinicalstudy procedures.

• Prospective participants who, in the opinion of the investigator, may not be able tocomply with all study procedures (including compliance issues related tofeasibility/logistics)