Ritlecitinib in CTCL

INCLUSION CRITERIA: * Age ≥ 18 years at time of enrollment * CTCL \>10% BSA involvement (stage IB-IVA by ISCL/EORTC staging criteria), previously confirmed by histopathology * CTCL subtypes eligible for this study include Mycosis fungoides and its subtypes, as well as Sézary Syndrome. * Failure of at least 2 skin-directed (ISCL/EORTC stage IB-IIA, i.e. early stage disease) or systemic treatments (ISCL/EORTC stage IIB-IVA, i.e. late stage disease) due to progression or toxicity as assessed by the prescribing physician or by the principal investigator, or insufficient response to established skin-directed or systemic treatments. i. Patients with documented CD30-positive CTCL must have previously received or be intolerant to brentuximab vedotin. * Adequate hematological (Hb\>9.0g/dl, absolute neutrophil count \>1200/ul, platelets \>75x10\^9/L, absolute \[non-malignant\] lymphocyte count \>800/ul), hepatic (AST and ALT \<2x times upper limit of normal), and renal function (eGFR \[CKD-EPI creatinine equation \>50mL/min/1.73m2) * ECOG ≤ 2 (Eastern Cooperative Oncology Group scoring system used to quantify general well-being and activities of daily life; scores range from 0 to 5 where 0 represents perfect health and 5 represents death.) * Ability to take oral medication without crushing, dissolving or chewing tablets * Ability to understand and the willingness to sign a written informed consent * In the investigator's opinion, the patient has the ability to communicate satisfactorily with the investigator and the study team, to participate fully in the study, and comply with all requirements EXCLUSION CRITERIA: * History of, or a concurrent, clinically significant illness, medical condition or laboratory abnormality that, in the investigator's opinion, could affect the conduct of the study * Immunosuppressed by previous (within 4 weeks) or current systemic cytotoxic therapies, as evidenced by recurrent skin or systemic infections * Pregnant or breast-feeding women * Unwillingness or inability to use a contraception method during the time of participation in the trial. * Uncontrolled current illness, including, but not limited to the following: Ongoing or active infections requiring intravenous antimicrobials; symptomatic congestive heart failure defined as NYHA class III or IV; unstable angina pectoris within 6 months of study enrollment; history of myocardial infarction, stroke or intracranial hemorrhage within 6 months prior to enrollment; moderate to severe hepatic impairment (Child-Pugh class B or C); psychiatric illness or social situations that would limit compliance with study requirements * Previous or concurrent cancer that is distinct in primary site or histology form CTCL, except curatively treated basal or squamous cell carcinoma of the skin, and curatively treated malignant melanoma stage 0-1A with a low risk of recurrence/metastasis as per assessment of the investigator, cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta, Tis and T1) * Known HIV infection * Infected with Hepatitis B or Hepatitis C viruses * Patients with history of either untreated or inadequately treated latent or active TB infections/currently being treated for active TB. * Recent (within 21 days before baseline) major surgery * Patients who have history of single episode of disseminated HZ or disseminated HS or recurrent (\> 1 episode of) localized dermatomal HZ should be excluded. * Less than 28 days have elapsed since last radiation therapy, phototherapy or chemotherapy treatment or patient has not recovered from all clinically significant treatment-related toxicity as defined in discontinuation criteria. * Less than 3 months have elapsed since last oral JAK inhibitors and/or less than 4 weeks have elapsed since last topical JAK inhibitor. * Glucocorticosteroids when used systemically; the use of nasal and inhaled glucocorticosteroids will be allowed PRN; the use of topical glucocorticosteroids (low to mid-potency) will only be allowed when given at a stable dose \>4 weeks * Prior treatment with other concomitant investigational agents * Hypersensitivity or allergic reaction to compounds related to JAK inhibitors * Treatment with medication that might interfere with blood levels or have a major impact on the clinical readout of the study drug, as per discretion of the study investigator; best supportive care will be allowed at the discretion of the investigator (e.g. anti-emetics, skin care, pain medication, anti-thrombotic agents, herpes zoster prophylaxis) * Any gastrointestinal or metabolic condition that could interfere with the absorption of the oral medication * Ongoing other MF-directed treatments (such as topical corticosteroids and topical bexarotene) unless stable over a period of one month * Active alcohol and/or drug abuse * History of thrombosis/thromboembolic event, known coagulopathy * Additional skin disease that might interfere with MF clinical assessments * Patient has received a live attenuated vaccine ≤ 30 days prior to study screening * Have hearing loss with progression over the previous 5 years, or sudden hearing loss, or middle or inner ear disease such as otitis media, cholesteatoma, Meniere's disease, labyrinthitis, or other auditory condition that is considered acute, fluctuating, or progressive. * Patients who have received prohibited drugs that are CYP3A inducers within a 28 day or 5 half-lives (whichever is longer) period prior to the first dose of study intervention. * Patients with ALCL or other forms of CTCL other than MF or Sézary Syndrome.