Effectiveness of Concurrent Ultra-Low-Dose Total-Skin Electron Beam Therapy and Brentuximab Vedotin Given Quarterly Over 12 Months for Patients With Mycosis Fungoides

Inclusion Criteria:

1. Biopsy-confirmed mycosis fungoides in stage I-IV (APPENDICES 3 AND 4); the presenceof Sezary cells in the blood is acceptable at original diagnosis or at enrollmentinto the protocol, as long as the patient has current mycosis fungoides in the skinand the sesary cells in peripheral blood are < 1000 cells/ microlitre at the time ofenrollment.

2. Participants with relapsed/ refractory mycosis fungoides expressing at least 1% CD30are eligible.

3. Previous systemic anticancer therapy must have been discontinued at least 1 weekbefore treatment

4. In the case of myelosuppressive chemotherapy treatment may start once counts haverecovered including absolute WBC> 1000, platelets> 50K.

5. Topical or systemic steroids (equivalent to 10 mg/day of prednisone) may beconsidered if the dose of such steroids has been constant and their discontinuationmay lead to rebound flare in disease, adrenal insufficiency, and/or unnecessarysuffering, after discussion with the Principal Investigator.

6. 18 years of age or older

7. Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 3 (APPENDIX

8. No required wash-out period for prior therapies

9. HIV+ participants must be on stable antiretroviral treatment for 12 weeks before thefirst day of cycle 1 (C1D1), with CD4 count >200 within the 7 days before C1D1.

10. Ability to understand and the willingness to sign a written informed consentdocument.

Exclusion Criteria:

1. Concurrent use of other systemic anticancer agents or treatments (including steroidsunless adrenal insufficiency has been diagnosed) for mycosis fungoides or Sezarysyndrome

2. Grade 2 or greater neuropathy

3. Severe renal impairment (creatinine clearance [CrCL] <30 mL/min)

4. Moderate or severe hepatic impairment (Child-Pugh B or C; see APPENDIX 6 forChildPugh classification chart)

5. Women of reproductive potential must have a negative serum ß human chorionicgonadotropin (ß-HCG) pregnancy test within 1 week of C1D1. They should discusscontraception with the treating provider. And agree to use adequate birth controlmeasures (oral, implanted, or barrier methods) while on study Female participants ofchildbearing potential who are not abstinent and intend to be sexually active with anon sterilized male partner must use at least 1 highly effective method ofcontraception (Failure rate of <1% per year when used consistently and correctly)throughout the total duration of the drug treatment and the drug washout period asdetermined by your physician. Non-sterilized male partners of a female participantsof childbearing potential must use male condom plus spermicide throughout thisperiod. Cessation of birth control after this point should be discussed with aresponsible physician. Periodic abstinence, the rhythm method, and the withdrawalmethod are not acceptable methods of birth control. Female participants should alsorefrain from breastfeeding throughout this period. Highly effective contraceptivemethods:

• Combined (estrogen- and progestogen-containing) hormonal contraceptionassociated with inhibition of ovulation

• oral

• intravaginal

• transdermal

• Progestogen-only hormonal contraception associated with inhibition of ovulation

• oral

• injectable

• Implantable progestogen-only hormonal contraception associated with inhibitionof ovulation b

• Intrauterine device (IUD)c

• Intrauterine hormone-releasing system (IUS)c

• Bilateral tubal occlusion

• Surgical Sterilization

6. Receipt of systemic therapy for another primary malignancy (other than T-celllymphoma). Participants with more than one type of lymphoma may be enrolled afterdiscussion with the Principal Investigator

7. Underlying medical conditions including unstable cardiac disease, or other seriousillness that would impair the ability of participants to undergo treatment

8. Any other medical history, including laboratory results, deemed by the PrincipalInvestigator to be likely to interfere with participants participation in the study

9. Use of strong CYP3A4 inhibitors or inducers, or P-gp inhibitors, should be avoidedgiven the potential effect on exposure to monomethyl auristatin E.