Combining low-dose radiation therapy with brentuximab vedotin for mycosis fungoides

Inclusion Criteria:

1. Biopsy-confirmed mycosis fungoides in stage I-IV (APPENDICES 3 AND 4); the presence of Sezary cells in the blood is acceptable at original diagnosis or at enrollment into the protocol, as long as the patient has current mycosis fungoides in the skin and the sesary cells in peripheral blood are \< 1000 cells/ microlitre at the time of enrollment.
2. Participants with relapsed/ refractory mycosis fungoides expressing at least 1% CD30 are eligible.
3. Previous systemic anticancer therapy must have been discontinued at least 1 week before treatment
4. In the case of myelosuppressive chemotherapy treatment may start once counts have recovered including absolute WBC\> 1000, platelets\> 50K.
5. Topical or systemic steroids (equivalent to 10 mg/day of prednisone) may be considered if the dose of such steroids has been constant and their discontinuation may lead to rebound flare in disease, adrenal insufficiency, and/or unnecessary suffering, 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 5)
8. No required wash-out period for prior therapies
9. HIV+ participants must be on stable antiretroviral treatment for 12 weeks before the first 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 consent document.

Exclusion Criteria:

1. Concurrent use of other systemic anticancer agents or treatments (including steroids unless adrenal insufficiency has been diagnosed) for mycosis fungoides or Sezary syndrome
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 for ChildPugh classification chart)
5. Women of reproductive potential must have a negative serum ß human chorionic gonadotropin (ß-HCG) pregnancy test within 1 week of C1D1. They should discuss contraception with the treating provider. And agree to use adequate birth control measures (oral, implanted, or barrier methods) while on study Female participants of childbearing potential who are not abstinent and intend to be sexually active with a non sterilized male partner must use at least 1 highly effective method of contraception (Failure rate of \<1% per year when used consistently and correctly) throughout the total duration of the drug treatment and the drug washout period as determined by your physician. Non-sterilized male partners of a female participants of childbearing potential must use male condom plus spermicide throughout this period. Cessation of birth control after this point should be discussed with a responsible physician. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Female participants should also refrain from breastfeeding throughout this period. Highly effective contraceptive methods:

   * Combined (estrogen- and progestogen-containing) hormonal contraception associated 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 inhibition of 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-cell lymphoma). Participants with more than one type of lymphoma may be enrolled after discussion with the Principal Investigator
7. Underlying medical conditions including unstable cardiac disease, or other serious illness that would impair the ability of participants to undergo treatment
8. Any other medical history, including laboratory results, deemed by the Principal Investigator 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 avoided given the potential effect on exposure to monomethyl auristatin E.