Venetoclax for the Treatment of Stage IB-IV Cutaneous T Cell Lymphoma

Inclusion Criteria

• Biopsy-confirmed CTCL (subtypes mycosis fungoides and Sezary syndrome only, and excluding transformed mycosis fungoides) stage IB-IV (hereafter referred to as advanced stage). An off-site biopsy report confirming CTCL diagnosis is acceptable. All subjects must have shown disease refractory to one or more standard systemic therapy (psoralen plus ultraviolet A [PUVA], oral bexarotene, vorinostat, romidepsin, and/or photopheresis) and/or to total skin electron beam therapy over a 3-month period, or have demonstrated relapsed or progressive disease at any time while receiving one or more of these therapies
• Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
• White blood cell (WBC) > 2000/uL, without use of colony stimulating factors (CSF)
• Platelet count > 75,000/mm^3, without use of colony stimulating factors (CSF)
• Neutrophil count > 1000/uL, without use of colony stimulating factors (CSF)
• Required washout period for prior CTCL therapies * Local skin radiation therapy (=<10% skin surface): 4 weeks * Systemic therapies: 4 weeks, or until recovered from toxicities
• Patients receiving moderate / strong CYP3A and P-gp inhibitors are not eligible for inclusion unless these agents are discontinued for a washout period of 4 weeks. These medications will not be allowed at initiation or during the ramp-up phase. These medications may be added back, if medically necessary, after the ramp-up phase is complete. * Moderate / strong CYP3A: (e.g. erythromycin, ciprofloxacin, clarithromycin, conivaptan, diltiazem, dronedarone, fluconazole, indinavir, itraconazole, lopinavir, ketoconazole, posaconazole, ritonavir, telaprevir, verapamil, voriconazole) * P-gP inhibitors (e.g., amiodarone, azithromycin, captopril, carvedilol, cyclosporine, digoxin, fexofenadine, felodipine, loperamide, quercetin, quinidine, ranolazine, talinolol, ticagrelor, vinblastine)
• Women of child-bearing potential must have negative serum pregnancy test and use accepted highly effective methods of birth control throughout the study and for 90 days after dosing and must agree to use effective contraception, such as hormonal birth control (must be at least 3 years without complications), intrauterine devices, double barrier method (condom plus spermicide or diaphragm), or abstain from sexual intercourse
• Male patients must be willing to use an appropriate method of contraception (e.g., condoms) or abstain from sexual intercourse and inform any sexual partners that they must also use a reliable method of contraception during the study and for 90 days after dosing
• Bilirubin =< 1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) =< 3.0 x ULN
• Alanine aminotransferase (ALT) =< 3.0 x ULN
• Alkaline phosphatase (liver fraction) =< 3.0 x ULN
• Creatinine clearance >= 50 mL/min
• Ability to comply with the treatment schedule

Exclusion Criteria

• Extracutaneous disease except blood, bone marrow and lymph nodes
• Concomitant use of any systemic anti-cancer therapy or immune modifier
• Concomitant use of moderate or strong CYP3A inhibitors or inducers within 1 week of initiation of study drug administration
• Patients with biopsy confirmed transformed mycosis fungoides (MF)
• Prior allogeneic hematopoietic cell transplant
• Any ongoing infection requiring antibiotics within 2 weeks prior to the start of the study drug, except for antibiotics (e.g. cephalexin) prescribed superficial skin infection
• Known history of human immunodeficiency virus (HIV), hepatitis B or C
• History of prior malignancy with the exception of cervical intraepithelial neoplasia, nonmelanoma skin cancer, and adequately treated localized prostate carcinoma (PSA < 1.0). Patients with a history of other malignancies must have undergone potentially curative therapy and have no evidence of that disease for five years
• Uncontrolled intercurrent illness, condition, or circumstances that could limit compliance with the study, including, but not limited to the following: acute or chronic graft versus host disease, uncontrolled diabetes mellitus or hypertension, or psychiatric conditions
• Major surgery within 8 weeks of enrollment
• Medically significant cardiac event or unstable cardiovascular function defined as: * Symptomatic ischemia, unstable angina pectoris * Uncontrolled clinically significant cardiac arrhythmia * Symptomatic heart failure New York Heart Association (NYHA) class >= 3 * Myocardial infarction or cardiac surgery within 6 months prior to enrollment
• Cerebrovascular event (transient ischemic attack, stroke or central nervous system [CNS] bleeding) within the last 12 months
• Major bleeding within the last 6 months
• Use of any investigational agents within 30 days prior to enrollment and for the duration of the study
• Pregnant or lactating
• Unwilling or unable to provide informed consent