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

NCT01007448 | Completed Phase 4 Results

• 1 other identifier: E7273-G000-401
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 17

Brief 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.

Conditions

Refractory Cutaneous T-cell Lymphoma

Keywords

CTCL; bexarotene; Targretin; Refractory Cutaneous T-cell Lymphoma; cutaneous T-cell Lymphoma; MF; Mycoses fungoides

Outcome Measures

Primary Outcomes (3)

• Number of Participants With Tumor Response (Complete Response [CR], Clinical Complete Response [CCR], and Partial Response [PR]) in up to 5 Index Lesions as Determined by Investigator's Composite Assessment (CA) of Index Lesion Disease Severity

  Index lesion symptoms/grade include: erythema=0 (no evidence)-8 (very severe); scaling=0 (no evidence)-8 (very severe); plaque elevation=0 (no evidence)-8 (extreme elevation); hypopigmentation/hyperpigmentation=0 (no evidence of change)-8 (very severe change); area of involvement=0 (0 centimeters \[cm\]\^2)-18 (\>300 cm\^2). CA generated by sum of grades of signs/symptoms for each index lesion. Index lesion CA grade at baseline was divided into CA grade at each subsequent study visit to determine participant's response to treatment. Ratio of CA \<1.0=improvement in disease; ratio \>1.0=worsening of disease. Tumor response as determined by CA=percentage of participants achieving CR (CA ratio=0, no clinically abnormal lymph nodes, and absence of histologic signs of CTCL); CCR (CA ratio=0 and no clinically abnormal lymph nodes); and PR (CA ratio=≤0.5, \<25% increase in number/aggregate area of abnormal lymph nodes/tumors, and no new abnormal lymph nodes in documented area of absence of disease).

  Baseline up to Week 24

• Number of Participants With Tumor Response of CR, CCR, PR, SD, and PD as Determined by Physician's Global Assessment (PGA) of Clinical Condition

  The PGA was an assessment of the overall extent of improvement/worsening from Baseline of the participant's overall disease compared with the condition every 4 weeks thereafter during treatment. CR=PGA grade of 0 (completely clear of disease since Baseline) and absence of histologic signs of CTCL. CCR=PGA grade of 0. PR=PGA grade of 1 (almost clear \[≥90%-\<100%\] of disease since Baseline), 2 (marked improvement \[≥75%-\<90%\] of disease since Baseline), 3 (moderate improvement \[≥50%-\<70%\] of disease since Baseline). Stable Disease (SD)=PGA grade of 4 (slight improvement \[\<25%-\<50%\] of disease since Baseline) or 5 (no change in disease \[+/-\<25% change since Baseline\]). Progressive Disease (PD)=PGA grade of 6 (worse disease \[≥25%\] than at baseline). If visceral disease or an abnormal lymph node was located in a documented area of absence of disease, then PD would be reported for the participant.

  Baseline up to Week 24

• Number of Participants With Tumor Response of CR, CCR, PR, SD, and PD as Determined Percent Body Surface Area (BSA) Involvement

  To determine BSA involvement, the area of the participant's palm was defined as 1% of the participant's BSA. The extent of involvement of disease was determined as multiples of the participant's palm area and expressed as a percentage of the participant's total BSA at Baseline (Day 1) and every 4 weeks thereafter during treatment. CR=percent BSA 0% and documented absence of histologic signs of CTCL. CCR=Percent BSA 0%. PR=a decrease from Baseline in percent BSA of at least 50%. SD=none of the response classifications (that is, CR, CCR, PR, or PD) accurately describe the disease status. PD=an increase from Baseline in percent BSA of at least 25%.

  Baseline up to Week 24

Secondary Outcomes (9)

• Duration of Tumor Response (CR, CCR, or PR) as Determined by Investigator's CA of Index Lesion Disease Severity

  Baseline up to Week 24

• Duration of Tumor Response (CR, CCR, or PR) as Determined by PGA of Clinical Condition

  Baseline up to Week 24

• Duration of Tumor Response (CR, CCR, or PR) as Determined by Percent BSA Involvement

  Baseline up to Week 24

• Time to Tumor Response (CR, CCR, or PR) as Determined by CA of Index Lesion Disease Severity

  Baseline up to Week 24

• Time to Tumor Response (CR, CCR, or PR) as Determined by PGA of Clinical Condition

  Baseline up to Week 24

Study Arms (2)

Bexarotene 150 milligrams (mg)/square meter (m^2)/day

EXPERIMENTAL

Participants will receive bexarotene 150 mg/m\^2/day once daily for 24 weeks.

Drug: Bexarotene

Bexarotene 300 mg/m^2/day

EXPERIMENTAL

Participants will receive bexarotene 300 mg/m\^2/day once daily for 24 weeks.

Drug: Bexarotene

Interventions

Bexarotene DRUG

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.

Also known as: Targretin®

Bexarotene 150 milligrams (mg)/square meter (m^2)/day; Bexarotene 300 mg/m^2/day

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A CTCL without central nervous system (CNS) involvement, confirmed by biopsy to be histologically consistent with CTCL diagnosis by a dermatopathologist.
• 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.)
• Systemic therapy for CTCL is indicated.
• A Karnofsky performance score ≥60%.
• Age ≥18 years.
• 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.
• 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.
• Must be willing and able to give informed consent and complete and understand, either oral or written, study procedures and assessments.
• Participant must be suitable for participation in the study in the Investigator's opinion.
• Fasting serum triglyceride within normal limits (\<150 mg/deciliter \[dL\]) prior to study entry.
• 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.
• 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.
• 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.

You may not qualify if:

• Cutaneous T-cell lymphoma involving the central nervous system.
• 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).
• Participation in any other investigational drug study within 30 days of entry in this study.
• Within 5 years after the onset of menopause.
• Received systemic corticosteroids within 6 months of entry in the study.
• Known hypersensitivity to bexarotene or other component of bexarotene capsules.
• Pregnancy, intent to become pregnant, or breast-feeding.
• Received gemfibrozil within 1 day of starting the study.
• Prior therapy for the treatment of CTCL:
• Psoralens and ultraviolet A light (PUVA) or ultraviolet B light (UVB) therapy within 3 weeks of study entry.
• Electron beam radiation therapy (EBT) or photopheresis within 3 weeks of study entry.
• 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.
• 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.

Sponsors & Collaborators

• Bausch Health Americas, Inc.: lead

Study Sites (17)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

Florida Academic Dermatology Centers

Miami, Florida, 33136, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Rush University

Chicago, Illinois, 60612, United States

Location

Tulane

New Orleans, Louisiana, 70112, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

University of Minnesota Medical School

Minneapolis, Minnesota, 55455, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Wake Forest University Health

Winston-Salem, North Carolina, 27157, United States

Location

University Hospitals-Case Medical Center

Cleveland, Ohio, 44106, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Vanderbilt

Nashville, Tennessee, 37206, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Huntsman Cancer Institute At the University of Utah

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Conditions

Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides

Interventions

Bexarotene

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Results Point of Contact

• Title: Director of Clinical Operations
• Organization: Bausch Health Americas, Inc.

aloncaric@bauschhealth.com

Study Officials

• Mandeep Kaur, MD

  Valeant Pharmaceutical NA

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2009
• First Posted: November 4, 2009
• Study Start: January 6, 2010
• Primary Completion: February 20, 2014
• Study Completion: February 20, 2014
• Last Updated: November 12, 2019
• Results First Posted: November 12, 2019

Record last verified: 2019-11

Locations

US (17)