Mogamulizumab and Low-Dose Total Skin Electron Beam Therapy for the Treatment of Stage IB-IV Mycosis Fungoides and Sezary Syndrome

Inclusion Criteria

• Stages IB-IV mycosis fungoides (MF) or Sezary syndrome (SS)
• 1 prior standard-of-care therapy
• Prior LD-TSEBT (> 3 months prior) and prior mogamulizumab is allowed, as long as progressive disease (PD) did not occur while on therapy, and did not discontinue due to toxicities
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
• All clinically-significant toxic effects of prior cancer therapy resolved to grade =< 1 by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI-CTCAE, v 5.0)
• MF and a known history of non-complicated staphylococcus colonization/infection is eligible provided that stable doses of prophylactic antibiotics continue
• The following minimum wash-out from previous treatments are required, if applicable * >= 4 weeks for retinoids, interferons, Vorinostat, romidepsin, pralatrexate, or other systemic anti-cancer/cutaneous T-cell non-Hodgkin lymphoma (CTCL) therapies * >= 2 weeks for phototherapy, local radiation therapy * >= 2 weeks for topical therapy (including topical steroid, retinoid, nitrogen mustard, or imiquimod) * >= 12 weeks for total skin electron beam therapy * >= 4 weeks for monoclonal antibodies; except > 12 weeks for alemtuzumab * Rapidly progressive malignant disease may be enrolled prior to above periods after discussion with the protocol director
• Absolute neutrophil count (ANC) >= 1,500 cells/uL (>= 1,500/mm^3); or if known bone marrow involvement, then ANC >= 1,000 cells/uL (>= 1,000/mm^3)
• Platelets >= 100,000 cells/uL (>= 100,000/mm^3); or if known bone marrow involvement, then platelets >= 75,000 cells/uL (>= 75,000/mm^3)
• Bilirubin =< 1.5 times the specific institutional upper limit of normal (ULN). Exception: If Gilbert’s syndrome; then =< 5 times ULN
• Aspartate transaminase (AST) and alanine transaminase (ALT) each =< 2.5 x ULN; or =< 5.0 x ULN in the presence of known hepatic involvement by CTCL
• Serum creatinine =< 1.5 x ULN; or calculated creatinine clearance > 50 mL/min using the Cockcroft-Gault formula
• If prior allogeneic hematopoietic stem cell transplant (HSCT), then must be free of graft-vs-host disease (GvHD) and receiving immunosuppressive therapy
• Women of childbearing potential (WOCBP) must have a negative pregnancy test
• WOCBP must agree to use effective contraception during the study and for 3 months after the last dose
• Male participants and their female partners of child bearing potential must be willing to use an appropriate method of contraception during the study and for 3 months after the last dose

Exclusion Criteria

• MF with limited disease (stage IA) or central nervous system (CNS) disease
• Current evidence of large cell transformed disease
• Concomitant corticosteroid use. (Topical steroid and oral prednisone are allowed at =< 20 mg/day, if patient has been on a stable dose for at least 4 weeks prior to study entry)
• Pregnant or breastfeeding
• Active autoimmune disease or history deemed by the investigator to be clinically significant
• Known human immunodeficiency virus (HIV) positivity; known human T-cell lymphotropic virus (HTLV-1) infection; or active hepatitis B or C
• Active herpes simplex or herpes zoster. Those receiving prophylaxis for herpes and who started taking medication at least 30 days prior to the screening visit, and have no active signs of active infection, and whose last active infection was more than 6 months ago, may enter the study, and should continue to take the prescribed medication for the duration of the study