The purpose of this study is to test any good and bad effects of the study drug called brentuximab vedotin at a lower dose than is FDA-approved.

Inclusion Criteria:

Mycosis fungoides (MF) and Sezary Syndrome (SS)

1. Pathologically confirmed mycosis fungoides/sezary syndrome at the enrolling institution, disease stage IB (defined as patches, plaque, or papules that involve 10% of the skin surface viscera) or higher

   ° CD30 negative mycosis fungoides patients are eligible.

2. Age ≥ 18 years

3. ECOG Performance Score ≤ 2

4. For Cohort 1, patients who have not received brentuximab vedotin are eligible.

5. For Cohort 2, patients who have previously had brentuximab vedotin for MF/SS are eligible. Patients previously treated on Cohort 1 who were discontinued due to toxicity are not eligible for Cohort 2.

6. Previous systemic anti-cancer therapy must have been discontinued at least 2 weeks prior to treatment.

   ° See section 6.2 Subject Exclusion Criteria for guidelines regarding adjuvant and maintenance therapy for prior malignancy.

7. Topical or systemic steroids (equivalent to ≤ 10 mg/day of prednisone) may be considered if dose has been constant and discontinuation may lead to rebound flare in disease, adrenal insufficiency, and/or unnecessary suffering, after discussion with PI.

8. If HIV+, patient must be on stable anti-retroviral treatment for 12 weeks prior to C1D1, with CD4 count >200 within 7 days prior to C1D1.

9. Females of childbearing potential must be on acceptable form of birth control per instutional standard.

Lymphomatoid papulosis (LyP)

1. Pathologically confirmed lymphomatoid papulosis at the enrolling institution
2. Requiring systemic treatment per investigator's discretion
3. Age ≥ 18 years
4. ECOG Performance Score ≤ 2
5. Previous systemic anti-cancer therapy must have been discontinued at least 2 weeks prior to treatment.
6. Topical or systemic steroids (equivalent to ≤ 10 mg/day of prednisone) may be considered if dose has been constant and discontinuation may lead to rebound flare in disease, adrenal insufficiency, and/or unnecessary suffering.
7. If HIV+, patient must be on stable anti-retroviral treatment for 12 weeks prior to C1D1, with CD4 count >200 within 7 days prior to C1D1.
8. Females of childbearing potential must be on acceptable form of birth control per institutional standard

Exclusion Criteria:

1. Concurrent use of other systemic anti-cancer agents or treatments for mycosis fungoides/sezary syndrome, or lymphomatoid papulosis.

2. Grade 2 or greater neuropathy

3. Severe renal impairment (CrCL <30 mL/min)

4. Moderate or severe hepatic impairment (Child-Pugh B or Child-Pugh C)

   ° See Appendix E for Child Pugh 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 treating provider.

6. Previous use of brentuximab vedotin (for Cohort 1 ONLY)

7. Receiving systemic therapy for another primary malignancy (other than T-cell lymphoma).

   • Patients with more than one type of lymphoma may be enrolled after discussion with the MSK Principal Investigator.
   • Adjuvant or maintenance therapy to reduce the risk of recurrence of other malignancy (other than T-cell lymphoma) is permissible after discussion with the MSK Principal Investigator.

8. For Cohort 2, patients who previously progressed on the standard 1.8mg/kg dose and schedule of brentuximab vedotin are ineligible.

   • A female of reproductive potential is a sexually mature female who: has not undergone a hysterectomy or bilateral oophorectomy; or has not been naturally postmenopausal for at least 24 consecutive months (i.e. has had menses at any time in the preceding 24 consecutive months).