Phase IV Randomized Study Of Two Dose Levels Of Targretin~ Capsules In Patients With Refractory Cutaneous T-Cell Lymphoma
1. A clinical diagnosis of cutaneous T-cell lymphoma (CTCL) without central nervous
system (CNS) involvement, confirmed by biopsy to be histologically consistent with
CTCL diagnosis by a dermatopathologist.
2. Refractory to at least one systemic therapy for CTCL. (Refractory is defined as
resistance to therapy due either to lack of response of at least 50% improvement or
progression of disease while still on therapy after an initial response).
3. Systemic therapy for CTCL is indicated.
4. A Karnofsky performance score ≥ 60%.
5. Age ≥18 years.
6. Females of childbearing potential must have a negative serum beta human chorionic
gonadotropin (ß-hCG) with a sensitivity of at least 50 mIU/L within seven days prior
to the initiation of treatment. Females of childbearing potential must have used
simultaneously two highly effective methods of contraception (strongly recommended
that one of the two forms of contraception be non-hormonal such as condom plus
spermicide, condom plus diaphragm with spermicide, or have a vasectomized partner) or
use an intrauterine device or must have been sexually abstinent for at least four
weeks prior to or at least one menstrual cycle prior to (whichever is longer) the
negative pregnancy test through entry in the study. Sexual abstinence or effective
contraception must be used for at least one month prior to the initiation of therapy,
during therapy, and for at least one month following discontinuation of therapy.
Perimenopausal women must be amenorrheic for at least 12 months to be considered of
7. Male patients with female partners of childbearing potential must agree to sexual
abstinence or to practice two reliable forms of effective contraception used
simultaneously (strongly recommended that one of the two forms of contraception be
non-hormonal such as condom plus spermicide, condom plus diaphragm with spermicide,
or partner with tubal ligation) or partner may use an intrauterine device, during the
entire period of Targretin capsule treatment and for at least one month after
treatment is discontinued. Male patients with female sexual partners who are
pregnant, possibly pregnant or who could become pregnant during the study must agree
to use condoms during sexual intercourse during the entire period of Targretin
capsule treatment and for at least one month after the last dose of Targretin
8. Must be willing and able to give informed consent, complete and understand, either
oral or written, study procedures and assessments.
9. Patient must be suitable for participation in the study in the investigator's
10. Fasting serum triglyceride within normal limits (<150 mg/dL) prior to study entry.
11. Adequate renal function as evidenced by serum creatinine ≤ 2.0 mg/dL or calculated
creatinine clearance ≥ 40 mL/min as per the Cockroft and Gault formula.
12. Adequate hepatic function that is characterized by aspartate aminotransferase (SGOT
[AST]), alanine aminotransferase (SGPT [ALT]), or serum bilirubin < 2.5 times the
upper limit of normal.
13. Adequate bone marrow function as evidenced by hemoglobin ≥ 8 g/dL, absolute
neutrophil count (ANC) ≥ 1,000/mm3, and platelets ≥ 50,000/mm3.
1. Cutaneous T-cell lymphoma involving the central nervous system.
2. Patients with known Human Immunodeficiency Virus (HIV) infection and active Hepatitis
B Virus (HBV) or Hepatitis C Virus (HCV) infection (HBV/ HCV or HIV testing is not
required for the purpose of this study)
3. Participation in any other investigational drug study within thirty (30) days of
entry in this study.
4. Within five (5) years after the onset of menopause.
5. Received systemic corticosteroids within six (6) months of entry in the study.
6. Known hypersensitivity to bexarotene or other component of Targretin capsules.
7. Pregnancy, intent to become pregnant, or breast-feeding.
8. Received gemfibrozil within one (1) day of starting the study.
9. Prior therapy for the treatment of CTCL:
1. PUVA or UVB therapy within three (3) weeks of study entry
2. EBT or photopheresis within three (3) weeks of study entry
3. Topical retinoids, nitrogen mustard, BCNU, imiquimod, etc. within two (2) weeks
of study entry If antipruritic medication cannot be avoided, antihistamine or
antipruritic agents must be administered using a stable dose regimen for at
least one (1) week prior to initiation of study drug treatment and throughout
the study, unless it is determined that a discontinuation or reduction in dose
is indicated. Prior to the enrollment of any patient who will be taking systemic
or dermatologically-applied antihistamine or anti-pruritic agent, the
investigator must contact Eisai to discuss the need for such agent. Mineral
oil, baby oil, and simple moisturizing lotions may be used as emollients. Low-
to mid- potency topical corticosteroids are allowed ONLY for patients with
erythroderma (stage III/IV CTCL) using a stable dose regimen for at least four
(4) weeks prior to study entry. High potency topical corticosteroids and tar
baths are NOT permitted.
NOTE: Prior to the enrollment of any patient who will be taking systemic or
dermatologically-applied antihistamine or anti-pruritic agent, the investigator
must contact the Sponsor to discuss the need for such agent.
4. Anticancer therapy of any kind (e.g., methotrexate, cyclophosphamide,
vorinostat, romidepsin, interferon, etc) within thirty (30) days of entry to the
study. Patient must recover from all signs of toxicity prior to entry in the
5. Oral retinoid therapy for any indication within three (3) months of study entry
6. Systemic therapy with Vitamin A in doses of greater than 15,000 IU (5,000 mcg)
per day (equivalent to approximately three times RDA) within thirty (30) days of
entry in this study).
10. Systemic antibiotic therapy within two (2) weeks of entry in the study. (Patients
with infections requiring antibiotics or likely to require antibiotics should be
appropriately treated with a course of antibiotics terminating at least two weeks
prior to entry, or if indicated, a chronic suppressive or prophylactic dose of
antibiotics stabilized at least two (2) weeks prior to entry. Patients who require
initiation of or changes in antibiotic therapy during the study will not be
considered a violation of this protocol).
11. History of pancreatitis or significant risk factors for developing pancreatitis
(e.g., prior pancreatitis, uncontrolled hyperlipidemia, excessive alcohol
consumption, uncontrolled diabetes mellitus, biliary tract disease, and medications
known to increase triglyceride levels or to be associated with pancreatic toxicity).
12. Unwillingness or inability to minimize exposure to sunlight and artificial
ultraviolet light while receiving Targretin capsules.