Brentuximab Vedotin in Combination with Mogamulizumab in Treating Patients with Stage II-IV Sezary Syndrome or Mycosis Fungoides

Inclusion Criteria

• Patient must be able to understand and comply with study procedure, understand the risks involved in the study and provide written informed consent before the first study-specific procedure
• Men or women >= 18 years with pathologically confirmed diagnosis of sezary syndrome/mycosis fungoides
• Participant must have CD30 positivity on most recent biopsy of >= 1%
• Participant must have stage II-IV of SS or MF. For participants with skin only disease, more than 20% body surface area should be involved. Participants with large cell transformation is allowed
• Participants must have received at least one prior systemic therapy like bexarotene, interferons, extracorporeal photopheresis (ECP), methotrexate, gemcitabine, vorinostat etc. (participants who have received only skin directed therapy are not allowed)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0,1 or 2
• Total bilirubin (T bili) < 2 X upper limit of normal (ULN), isolated bilirubin of =< 3 is accepted if there is suspected diagnosis of Gilbert’s syndrome
• Aspartate aminotransferase (AST) and alanine transaminase (ALT) < 3X ULN
• Estimated creatinine clearance (CrCl) of at least 30mL/min
• Left ventricular ejection fraction (LVEF) >= 40%
• Participants must have completed any chemotherapy or biologic therapy specific to the MF/SS >= 1 weeks or 5 half-lives (whichever is longer). Radiation for palliation on symptomatic lesions has no wash out period
• Expected life >= 4 months
• Participants with a prior history of stem cell transplant (autologous and/or allogeneic) are allowed if all of the following are met: * 180 days or more have elapsed from the time of transplant * Participants have been off systemic immunosuppressive medications (including but not limited to: cyclosporine, tacrolimus, mycophenolate mofetil, or corticosteroids) for at least 30 days prior to cycle 1 day 1 (C1D1) * No signs or symptoms of acute graft versus host disease * No signs or symptoms of chronic graft versus host disease requiring systemic therapy
• Women of child-bearing potential (according to recommendations of the Clinical Trial Facilitation Group [CTFG], CTFG 2014) must not be pregnant or breastfeeding and must have a negative pregnancy test at screening. A woman is considered of childbearing potential (i.e., fertile) following menarche and until becoming postmenopausal, unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. A man is considered fertile after puberty unless permanently sterile by bilateral orchidectomy
• Participants and their partners with reproductive potential must agree to use 2 highly effective contraceptive measures during the study and must agree not to become pregnant or father a child for 6 months after the last dose of study treatment. Contraceptive measures that may be considered highly effective comprise combined hormonal contraception (oral, vaginal, or transdermal) or progestogen-only hormonal contraception (oral, injectable, implantable) associated with inhibition of ovulation, intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, sexual abstinence, and surgically successful vasectomy. Abstinence is acceptable only if it is consistent with the preferred and usual lifestyle of the participant. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are not acceptable methods of birth control
• Prior severe allergic or anaphylactic reaction to monoclonal antibody or BV

Exclusion Criteria

• Participants with prior exposure of BV or mogamulizumab (moga). Prior exposure of BV is allowed if it is >= 6 months ago and CD30+ in >= 1% of tumor cells in biopsy after last BV
• Active central nervous system (CNS) involvement by MF/sezary syndrome
• Participant should not be receiving any other investigational agents. Prior use of investigational agents or other systemic therapy is allowed if it is >= 1 week ago or 5x half-life of the investigational agent whichever is shorter
• Pregnant or lactating women
• Severe or uncontrolled systemic infection. (active skin infections in cutaneous T-cell lymphoma [CTCL]/MF participants are allowed once course of antibiotics is completed and infection is under control)
• Known HIV infection
• Active hepatitis B or C infection. Hepatitis B core positive and hepatitis B surface antigen (HBsAg) positivity are allowed if hepatitis B virus (HBV) deoxyribonucleic acid (DNA) in blood is negative. Participants with chronic hepatitis B infection with active disease who meet criteria for anti HBV therapy should be on suppressive antiviral therapy. Hepatitis C positivity is allowed but hepatitis C virus (HCV) DNA by polymerase chain reaction (PCR) must be negative in peripheral blood
• Child-Pugh B or worse hepatic dysfunction
• Uncontrolled diabetes mellitus (DM), hypertension (HTN), New York Heart Association (NYHA) grade III-IV congestive heart failure (CHF), unstable angina, myocardial infarction within past 3 months, uncontrolled cardiac arrhythmia, uncontrolled psychiatric illness/social situation that would limit compliance with study requirements in the opinion of the investigator
• Grade 2 or more peripheral sensory or motor neuropathy
• History of solid organ transplant
• History of another malignancy, excluding non-melanoma skin cell cancer and any other localized cancer which per investigator is thought to be cured, within past 2 years
• History of any active autoimmune disease (except endocrine) requiring systemic immunosuppression
• Participants with active pneumonitis
• Any active acute or chronic graft versus host disease in participants with prior allogeneic