The purpose of this study is to determine the efficacy of the combination of LD-TSEBT and mogamulizumab in patients with MF and SS. And to evaluate the secondary measures of clinical benefit of the combination therapy and to evaluate the safety and tolerability of the combination in patients with MF and SS.

Primary Objective:To determine the efficacy of the combination of LD TSEBT and mogamulizumab in patients with MF and SS

Secondary Objective: To evaluate the secondary measures of clinical benefit of the combination therapy and to evaluate the safety and tolerability of the combination in patients with MF and SS

Inclusion Criteria:

• Stages IB-IV MF or SS

  1. Stages IB-IV MF or SS

  2. At least 1 prior standard-of-care therapy

  3. 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

  4. ≥ 18 years of age

  5. ECOG performance status of 0 to 2

  6. 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).

  7. MF and a known history of non-complicated staphylococcus colonization/infection is eligible provided that stable doses of prophylactic antibiotics continue.

  8. The following minimum wash-out from previous treatments are required (prior to 1st day of treatment), if applicable.

     • ≥ 2weeks for retinoids, interferons, Vorinostat, romidepsin, pralatrexate, or other systemic anti-cancer/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

     • > 12 weeks for alemtuzumab

     • Rapidly progressive malignant disease may be enrolled prior to above periods after discussion with the Protocol Director.

  9. Adequate hematologic function

     • Absolute neutrophil count (ANC) ≥ 1,000 cells/μL (≥ 1,000/mm3)

     • Platelets ≥ 75,000 cells/μL (≥ 75,000/mm3).

  10. Adequate hepatic function

      • 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.

  11. Adequate renal function

      • Calculated creatinine clearance ≥ 30 mL/min using the Cockcroft-Gault formula.

  12. If prior allogeneic hematopoietic stem cell transplant (HSCT), then must be free of graft-vs-host disease (GvHD) and receiving immunosuppressive therapy.

  13. Women of childbearing potential (WOCBP) must have a negative pregnancy test.

  14. WOCBP must agree to use effective contraception during the study and for 3 months after the last dose.

  15. 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:

  1. MF with limited disease (Stage IA) or central nervous system (CNS) disease
  2. Concomitant corticosteroid use. (with the exception that topical steroid and oral prednisone are allowed at ≤ 20 mg/day, if patient has been on a stable dose for at least 2 weeks prior to 1st day of treatment)
  3. Pregnant or breastfeeding
  4. Active autoimmune disease or history deemed by the investigator to be clinically significant
  5. Known human immunodeficiency virus (HIV) positivity; or active hepatitis B or C.
  6. 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.