Purpose: This is a multicenter, randomized, open-label study of patients with refractory CTCL assessing the efficacy, tolerability, and safety of two initial dose levels of Targretin capsules.
Ages Eligible for Study:
18 Years and older
Genders Eligible for Study:
Accepts Healthy Volunteers:
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 not be pregnant. Females of childbearing potential must have used simultaneously two highly effective methods of contraception 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 nonchildbearing potential.
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) 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 capsules.
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 opinion.
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:
a. Psoralen Plus Ultraviolet-A radiation (PUVA) or Ultraviolet-B (UVB) therapy within three (3) weeks of study entry
b. Electron Beam Radiation Therapy (EBT) or photopheresis within three (3) weeks of study entry
c. Topical retinoids, nitrogen mustard, carmustine (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.
d. 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 study.
e. Oral retinoid therapy for any indication within three (3) months of study entry.
f. 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.
Contact: Lindsay Chandler, Clinical Research Coordinator, 801-587-4391, Lindsay.firstname.lastname@example.org
Clinicaltrials.gov identifier: NCT01007448