Study Evaluating Two Dose Levels of Targretin Capsules in Participants With Refractory Cutaneous T-Cell Lymphoma (CTCL)

Phase IV Randomized Study of Two Dose Levels of Targretin® Capsules in Subjects With Refractory Cutaneous T-Cell Lymphoma

This is a multicenter, randomized, open-label, Phase IV study to assess the efficacy, tolerability, and safety of 2 initial dose levels of bexarotene capsules in participants with refractory CTCL.

Inclusion Criteria:

1. A 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 1 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 milli-international units/liter (mIU/L) within 7 days prior to the initiation of treatment. Females of childbearing potential must have used simultaneously two highly effective methods of contraception (strongly recommended that 1 of the 2 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 1 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 1 month prior to the initiation of therapy, during therapy, and for at least 1 month following discontinuation of therapy. Perimenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential.
7. Male participants with female partners of childbearing potential must agree to sexual abstinence or to practice 2 reliable forms of effective contraception used simultaneously (strongly recommended that 1 of the 2 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 bexarotene capsule treatment and for at least 1 month after treatment is discontinued. Male participants 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 bexarotene capsule treatment and for at least 1 month after the last dose of bexarotene capsules.
8. Must be willing and able to give informed consent and complete and understand, either oral or written, study procedures and assessments.
9. Participant must be suitable for participation in the study in the Investigator's opinion.
10. Fasting serum triglyceride within normal limits (<150 mg/deciliter [dL]) prior to study entry.
11. Adequate renal function as evidenced by serum creatinine ≤2.0 mg/dL or calculated creatinine clearance ≥40 milliliters (mL)/minute (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 grams (g)/dL, absolute neutrophil count (ANC) ≥1,000/milliliters cubed (mm^3), and platelets ≥50,000/mm^3.

Exclusion Criteria

1. Cutaneous T-cell lymphoma involving the central nervous system.

2. Participants 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 30 days of entry in this study.

4. Within 5 years after the onset of menopause.

5. Received systemic corticosteroids within 6 months of entry in the study.

6. Known hypersensitivity to bexarotene or other component of bexarotene capsules.

7. Pregnancy, intent to become pregnant, or breast-feeding.

8. Received gemfibrozil within 1 day of starting the study.

9. Prior therapy for the treatment of CTCL:

   1. Psoralens and ultraviolet A light (PUVA) or ultraviolet B light (UVB) therapy within 3 weeks of study entry.

   2. Electron beam radiation therapy (EBT) or photopheresis within 3 weeks of study entry.

   3. Topical retinoids, nitrogen mustard, carmustine (BCNU), imiquimod, or other antipruritic medication within 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 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 participant 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 participants with erythroderma (Stage III/IV CTCL) using a stable dose regimen for at least 4 weeks prior to study entry. High potency topical corticosteroids and tar baths are NOT permitted.

      NOTE: Prior to the enrollment of any participant 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 (for example, methotrexate, cyclophosphamide, vorinostat, romidepsin, and interferon) within 30 days of entry to the study. Participant must recover from all signs of toxicity prior to entry in the study.

   5. Oral retinoid therapy for any indication within 3 months of study entry.

   6. Systemic therapy with Vitamin A in doses of greater than 15,000 International Units (IU) (5,000 microgram [mcg]) per day (equivalent to approximately 3 times Recommended Daily Allowance [RDA]) within 30 days of entry in this study.

10. Systemic antibiotic therapy within 2 weeks of entry in the study. (Participants 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 2 weeks prior to entry. Participants who require initiation of or changes in antibiotic therapy during the study will not be considered a violation of the study protocol).

11. History of pancreatitis or significant risk factors for developing pancreatitis (for example, 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 bexarotene capsules.