TSEB and Brentuximab for Treatment of Mycosis Fungoides & Sezary Syndrome

Inclusion Criteria: * Histologically confirmed CD30-positive (defined in this study as ≥ 1% expression) Mycosis Fungoides (including large cell transformation variant) or Sezary Syndrome who have either: * Received prior systemic therapy (for whom commercial supply of brentuximab vedotin is available) OR * Not received prior systemic therapy (who will receive brentuximab vedotin free of charge) * Any of the disease stages listed below * Stage IB disease that meets one of the following criteria: * Plaque disease (ie,T2b staging) * Diffuse skin involvement with indication for TSEB (plaque disease with or without patches) * Not appropriate for treatment with focal therapies * One prior course of low-dose TSEB or one prior course of systemic chemotherapy regimens (excluding brentuximab) * Stage IIA, IIB, or IIIA that meets ONE or BOTH of the following criteria: * Patient is a candidate for treatment with low-dose TSEB * Patient is a candidate for systemic therapy * IIIB or IVA disease requiring systemic therapy * Transformed CTCL * Candidate for TSEB based on investigator determination * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, 2, or 3, if the performance status of 3 is due to skin disease involvement * Adequate bone marrow function as defined below: * Absolute neutrophil count (ANC) ≥ 1000/mm3 * Platelets \> 75,000/mm3 * Hemoglobin ≥ 9 g/dL * Note: Patients requiring transfusion to meet the hemoglobin requirement are not eligible for the study. * Calculated creatinine clearance (CrCl) \> 30 mL/min. * Adequate hepatic function as defined below: * Total bilirubin ≤ 1.5 x ULN for the laboratory * Aspartate aminotransferase (AST) ≤ 2 x ULN for the laboratory * Alanine aminotransferase (ALT) ≤ 2 x ULN for the laboratory * Prothrombin time with INR ≤ ULN for the laboratory * A woman of childbearing potential (WCBP), defined as a woman who is \< 60 years of age and has not had a hysterectomy, must have a documented negative serum pregnancy test 14 days prior to study registration * Note: If study treatment is not initiated within 7 days after the pregnancy test, the pregnancy test must be repeated. * A WCBP and a male patient with a partner who is a WCBP must agree to use a medically accepted method for preventing pregnancy for the duration of study treatment and for at least 6 months following completion of study treatment * Ability to understand and willingness to sign the consent form Exclusion Criteria: * Previous TSEB therapy with total dose \> 20 Gy * Previous brentuximab treatment * Any of the following within 4-3 weeks prior to initiating study treatment * Systemic biologic therapy * Monoclonal antibody * Chemotherapy * TSEB * Phototherapy * Other investigational therapy * Anticancer topical therapy, including therapeutic doses of steroids, within 2 weeks prior to initiating study treatment * Note: Topical steroids at doses intended for symptom management are permitted prior to study enrollment and may continue during study treatment. * Peripheral sensory neuropathy or peripheral motor neuropathy ≥ grade 2 per NCI CTCAE v4.0 * Diabetic neuropathy (any grade) * Demyelinating form of Charcot-Marie-Tooth Syndrome * History of progressive multifocal leukoencephalopathy * Active or clinically significant cardiac disease including any of the following: * Unstable angina (eg, anginal symptoms at rest) or onset of angina within 3 months prior to initiating study treatment * Myocardial infarction within 6 months prior to initiating study treatment * New York Heart Association (NYHA) class III or IV congestive heart failure (Appendix 4) * Active ≥ grade 3 (per NCI CTCAE v4) viral, bacterial, or fungal infection within 2 weeks prior to initiation of study treatment * Known human immunodeficiency virus (HIV) infection * Known or suspected active hepatitis B or C infection * Known cirrhosis * Known Gilbert's Syndrome * Planned ongoing treatment with another drug that may potentially have adverse interactions with brentuximab vedotin; if such a drug has been used, it must be discontinued at least 1 week prior to initiating study treatment (see Section 6.6); examples of potential interactions include: * Coadministration of strong inhibitors of CYP3A4 (eg, ketoconazole, ritonavir, clarithromycin) * Coadministration of CYP3A4 inducers (eg, rifampin) * Concomitant treatment with strong inhibitors of P-glycoprotein (P-gp) * Known hypersensitivity to any excipient contained in the brentuximab formulation * Prior malignancy or myelodysplastic syndrome (active within 3 years of screening) except completely excised non-invasive basal cell or squamous cell carcinoma of the skin, and in situ squamous cell carcinoma of the cervix * Pregnancy or breastfeeding * Medical, psychological, or social condition that, in the opinion of the investigator, may increase the patient's risk or limit the patient's adherence with study requirements