| Eligibility |
Inclusion Criteria:
- Biopsy-confirmed CTCL (subtypes mycosis fungoides and Sézary 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 (PUVA, oral bexarotene, vorinostat, romidepsin, and/or Photopheresis) and/or
total skin electron beam therapy over 3 months, or have demonstrated relapsed or
progressive disease at any time while receiving one or more of therapies.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of = 2.
- Adequate bone marrow function: WBC > 2000/µL; platelet count > 75,000/mm3; Neutrophil
count > 1000/µL, without use of colony stimulating factors (CSF).
- Required washout period for prior therapies
1. Spot Skin Radiation Therapy (=10% skin surface): 4 weeks
2. Systemic therapy: 4 weeks, or until recovered from toxicities
- 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.
- Adequate hepatic function: bilirubin =1.5 x upper limit of normal (ULN), AST =3.0 x
ULN, ALT = 3.0 x ULN
- Adequate renal function: 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 receiving P-gp inhibitors are not eligible for inclusion unless these agents
are discontinued for a washout period of 4 weeks. Patients who are taking medications
that are narrow window index P-gp substrates (e.g. digoxin, fexofenadine, loperamide,
quinidine, talinolol, vinblastine) are not eligible for enrollment.
- Patients with biopsy confirmed transformed 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,
non-melanoma 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 NYHA Class = 3
- Myocardial infarction or cardiac surgery within 6 months prior to enrollment
- Cerebrovascular event (transient ischemic attack, stroke or 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.
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