Total Skin Electron Beam Radiation Therapy and Brentuximab Vedotin in Treating Patients with Stage IB-IVA Mycosis Fungoides, Sezary Syndrome, or Primary Cutaneous T-Cell Non-Hodgkin Lymphoma

Inclusion Criteria

• Histologically confirmed CD30-positive (defined in this study as >= 1% expression) MF (including large cell transformation variant) or SS 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 ALL 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 cutaneous T-cell lymphoma (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
• Absolute neutrophil count (ANC) >= 1000/mm^3
• Platelets > 75,000/mm^3
• 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
• Total bilirubin =< 1.5 x upper limit of normal (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 international normalized ratio (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 within 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 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 National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4.0
• 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
• 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; 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