Study Evaluating Two Dose Levels of Targretin Capsules in Participants With Refractory Cutaneous T-Cell Lymphoma (CTCL)
Condition: Refractory Cutaneous T-cell Lymphoma
MeSH terms: Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Lymphoma, T-Cell, Cutaneous
Intervention: Bexarotene
Intervention description: Soft gelatin capsules to be taken orally with at least 6 ounces of water or other fluid either with or immediately following the evening meal (a moderate or full meal) or a nutritionally defined liquid food.
Intervention MeSH terms: Bexarotene
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 59.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: CTCL; bexarotene; Targretin; Refractory Cutaneous T-cell Lymphoma; cutaneous T-cell Lymphoma; MF; Mycoses fungoides

Summary:

      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.
    

Eligibility criteria:

        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.