A Phase 2 Trial to Assess Safety and Efficacy of Tofacitinib 2% Cream in the Treatment of Cutaneous T-cell Lymphoma (CTCL), Stages IA, IB, and IIA

Inclusion Criteria:

• Age ≥18 years at screening visit. Because limited dosing and adverse event data arecurrently available on the use of tofacitinib in participants <18 years of age,children are excluded from this study.

• Have a clinical diagnosis of cutaneous T-cell lymphoma (CTCL) stage IA, IB, orIIA including documentation of a skin biopsy with histological findingsconsistent with CTCL.

• For stage IIA, only participants with a classification of N0 (no clinicallyabnormal peripheral lymph nodes) or N1 (clinically abnormal lymph node(s)histopathology Dutch grade 1 or NCI LN0-2) can be enrolled.

• Participants must be B0 (absence of significant blood involvement: .5% ofperipheral blood lymphocytes of <250/mcL are atypical.

• Have at least 2 distinct lesions that have either failed or recurred despitetreatment with 1 previous standard therapy.

• ECOG performance status ≤ 2 (Karnofsky .60%)

• Participants with a prior or concurrent malignancy whose natural history ortreatment does not have the potential to interfere with the safety or efficacyassessment of the investigational regimen are eligible for this trial.

• The effects of tofacitinib on the developing human fetus are unknown. Availabledata with tofacitinib in its oral formulation in pregnant women areinsufficient to establish a drug associated risk of major birth defects,miscarriage or adverse maternal or fetal outcomes. Therefore, women ofchild-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entryand for the duration of study participation. This includes all femaleparticipants, between the onset of menses (as early as 8 years of age) and 55years unless the participant presents with an applicable exclusionary factorwhich may be one of the following:

1. Postmenopausal (no menses in greater than or equal to 12 consecutivemonths)
2. History of hysterectomy or bilateral salpingo-oophorectomy
3. Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausalrange, who have received Whole Pelvic Radiation Therapy)
4. History of bilateral tubal ligation or another surgical sterilizationprocedure

• Approved methods of birth control are as follows: Hormonal contraception (i.e.birth control pills, injection, implant, transdermal patch, vaginal ring),Intrauterine device (IUD), Tubal Ligation or hysterectomy, Subject/Partner postvasectomy, Implantable or injectable contraceptives, and condoms plusspermicide. Not engaging in sexual activity for the total duration of the trialand the drug washout period is an acceptable practice; however periodicabstinence, the rhythm method, and the withdrawal method are not acceptablemethods of birth control. Should a woman become pregnant or suspect she ispregnant while she or her partner is participating in this study, she shouldinform her treating physician immediately.

• Men treated or enrolled on this protocol must also agree to use adequatecontraception prior to the study, for the duration of study participation, and 4 months after completion of tofacitinib administration.

• Ability to understand and the willingness to sign a written informedconsent document.

Exclusion Criteria:

• History of allergic reactions attributed to compounds of similar chemical orbiologic composition to tofacitinib

• Skin infection and/or skin ulceration at screening and baseline visit

• Any subject with a diagnosis of active malignancy or a cancer requiringtreatment of expected to require treatment during the course of the trial (notincluding basal cell carcinoma, squamous cell carcinoma of the skin, malignantmelanoma in situ, or cervical carcinoma in situ)

• Any uncontrolled or serious underlying disease or medical or surgical conditionthat may interfere with interpretation of the trial results and/or place thesubject at significant risk according to investigator discretion including butnot limited to severe cardiac, psychiatric, hematologic, and thyroid conditions

• History of Stage IIB or greater CTCL, or stage IIA CTCL with history of stageN2 (Dutch Grade 2 or NCI LN3 or greater), or with >5% circulating Sezary cells

• History of aggressive CD8+ CTCL disease

• Having received one of the following treatments within the specified timeframes (calculated from baseline visit):

• In the past 12 weeks: Total Skin Electron Beam Therapy (TSEBT)

• In the past 8 weeks: topical imiquimod

• In the past 4 weeks: topical corticosteroids, topical chemotherapy,topical retinoids, local radiation therapy, UVB therapy, PUVA,photopheresis, systemic retinoids, systemic corticosteroids, interferoninducers, systemic chemotherapeutic agents

• Participants who have not recovered from adverse events due to prioranti-cancer therapy (i.e., have residual toxicities > Grade 1) with theexception of alopecia

• Participants who are receiving any other investigational agents

• Participants with uncontrolled intercurrent illness

• Human immunodeficiency virus (HIV)-infected patients on effectiveanti-retroviral therapy with undetectable viral load within 6 months areeligible for this trial

• Participants with psychiatric illness/social situations that would limitcompliance with study requirements

• Pregnant women are excluded from this study because the effects of tofacitinibon the developing human fetus are unknown. As there is a potential risk foradverse events in nursing infants secondary to treatment of the mother withtofacitinib, breastfeeding should be discontinued if the mother is treated withtofacitinib. These potential risks may also apply to other agents used in thisstudy.