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

• Sponsor: Bausch Health Americas, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01007448
• Collaborator: (none)
• Enrollment: 59
• Locations: 17
• Arms: 2
• Actual Duration (Months): 49.5
• Patients Per Site: 3.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Refractory Cutaneous T-cell Lymphoma	Drug: Bexarotene	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 59 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase IV Randomized Study of Two Dose Levels of Targretin® Capsules in Subjects With Refractory Cutaneous T-Cell Lymphoma
• Actual Study Start Date: Jan 6, 2010
• Actual Primary Completion Date: Feb 20, 2014
• Actual Study Completion Date: Feb 20, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Bexarotene 150 milligrams (mg)/square meter (m^2)/day Participants will receive bexarotene 150 mg/m^2/day once daily for 24 weeks.	Drug: Bexarotene; 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.; Other Names: Targretin®
Experimental: Bexarotene 300 mg/m^2/day Participants will receive bexarotene 300 mg/m^2/day once daily for 24 weeks.	Drug: Bexarotene; 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.; Other Names: Targretin®

Outcome Measures

Primary Outcome Measures

1. 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 [Baseline up to Week 24]

   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).

2. Number of Participants With Tumor Response of CR, CCR, PR, SD, and PD as Determined by Physician's Global Assessment (PGA) of Clinical Condition [Baseline up to Week 24]

   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.

3. Number of Participants With Tumor Response of CR, CCR, PR, SD, and PD as Determined Percent Body Surface Area (BSA) Involvement [Baseline up to Week 24]

   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%.

Secondary Outcome Measures

1. Duration of Tumor Response (CR, CCR, or PR) as Determined by Investigator's CA of Index Lesion Disease Severity [Baseline up to Week 24]

   Defined as time interval from onset of response to time participant relapses or last date of data collected with an assessment of participant still meeting response criteria. Index lesion symptoms/grade: erythema/scaling=0 (no evidence)-8 (very severe); plaque elevation=0 (no evidence)-8 (extreme elevation); hypopigmentation/hyperpigmentation=0 (no evidence)-8 (very severe change); area of involvement=0 (0 cm^2)-18 (>300 cm^2). CA: sum of signs/symptoms grades for index lesion. Index lesion CA grade at baseline divided into CA grade at study visit to determine treatment response. CA Ratio <1.0=improvement and >1.0=worsening of disease. Tumor response=percentage of participants with CR (CA ratio=0, no clinically abnormal lymph nodes, absence of CTCL histologic signs); CCR (CA ratio=0; no clinically abnormal lymph nodes); PR (CA ratio=≤0.5, <25% increase in number/aggregate area of abnormal lymph nodes/tumors, no new abnormal lymph nodes in documented area of absence of disease).

2. Duration of Tumor Response (CR, CCR, or PR) as Determined by PGA of Clinical Condition [Baseline up to Week 24]

   Defined as time interval from onset of response to time participant relapses or last date of data collected with an assessment of participant still meeting response criteria. 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).

3. Duration of Tumor Response (CR, CCR, or PR) as Determined by Percent BSA Involvement [Baseline up to Week 24]

   Defined as time interval from onset of response to time participant relapses or last date of data collected with an assessment of participant still meeting response criteria. To determine BSA, 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%.

4. Time to Tumor Response (CR, CCR, or PR) as Determined by CA of Index Lesion Disease Severity [Baseline up to Week 24]

   Defined as time interval from first day of bexarotene treatment to time of first observation when participant met the criteria of CR, CCR, or PR. Index lesion symptoms/grade: erythema/scaling=0 (no evidence)-8 (very severe); plaque elevation=0 (no evidence)-8 (extreme elevation); hypopigmentation/hyperpigmentation=0 (no evidence)-8 (very severe change); and area of involvement=0 (0 cm^2)-18 (>300 cm^2). CA: sum of signs/symptoms grades for index lesion. Index lesion CA grade at baseline divided into CA grade at study visit to determine treatment response. CA Ratio <1.0=improvement and >1.0=worsening of disease. Tumor response=percentage of participants with CR (CA ratio=0, no clinically abnormal lymph nodes, and absence of CTCL histologic signs); 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).

5. Time to Tumor Response (CR, CCR, or PR) as Determined by PGA of Clinical Condition [Baseline up to Week 24]

   Defined as time interval from first day of bexarotene treatment to time of first observation when participant met the criteria of CR, CCR, or PR. 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).

6. Time to Tumor Response (CR, CCR, or PR) as Determined by Percent BSA Involvement [Baseline up to Week 24]

   Defined as time interval from first day of bexarotene treatment to time of first observation when participant met the criteria of CR, CCR, or PR. To determine BSA, 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%.

7. Time to Tumor Progression as Determined by CA of Index Lesion Disease Severity [Baseline up to Week 24]

   Defined as time interval from first day of bexarotene treatment to time of first observation when participant met criteria for PD. Index lesion symptoms/grade: erythema/scaling=0 (no evidence)-8 (very severe); plaque elevation=0 (no evidence)-8 (extreme elevation); hypopigmentation/hyperpigmentation=0 (no evidence)-8 (very severe change); and area of involvement=0 (0 cm^2)-18 (>300 cm^2). CA: sum of signs/symptoms grades for index lesion. Index lesion CA grade at baseline divided into CA grade at study visit to determine treatment response. CA Ratio <1.0=improvement and >1.0=worsening of disease. Criteria for PD requires at least 1 component of the following: CA ratio=≥1.25, ≥25% increase in number/aggregate area of abnormal lymph nodes/tumors, or no new abnormal lymph nodes in documented area of absence of disease.

8. Time to Tumor Progression as Determined by PGA of Clinical Condition [Baseline up to Week 24]

   Defined as time interval from first day of bexarotene treatment to time of first observation when participant met criteria for PD. 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. 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.

9. Time to Tumor Progression as Determined by Percent BSA Involvement [Baseline up to Week 24]

   Defined as time interval from first day of bexarotene treatment to time of first observation when participant met criteria for PD. 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. PD=an increase from Baseline in percent BSA of at least 25%.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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:

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

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

12. 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.

1. 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.

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

3. 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.

4. 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).

5. 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).

6. Unwillingness or inability to minimize exposure to sunlight and artificial ultraviolet light while receiving bexarotene capsules.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35233
2	Florida Academic Dermatology Centers	Miami	Florida	United States	33136
3	Emory University	Atlanta	Georgia	United States	30322
4	Rush University	Chicago	Illinois	United States	60612
5	Tulane	New Orleans	Louisiana	United States	70112
6	University of Michigan	Ann Arbor	Michigan	United States	48109
7	University of Minnesota Medical School	Minneapolis	Minnesota	United States	55455
8	Washington University	Saint Louis	Missouri	United States	63110
9	University of Rochester	Rochester	New York	United States	14642
10	Duke University	Durham	North Carolina	United States	27710
11	Wake Forest University Health	Winston-Salem	North Carolina	United States	27157
12	University Hospitals-Case Medical Center	Cleveland	Ohio	United States	44106
13	University of Pittsburgh	Pittsburgh	Pennsylvania	United States	15213
14	Vanderbilt	Nashville	Tennessee	United States	37206
15	University of Texas Southwestern Medical Center	Dallas	Texas	United States	75390
16	MD Anderson Cancer Center	Houston	Texas	United States	77030
17	Huntsman Cancer Institute At the University of Utah	Salt Lake City	Utah	United States	84112

Sponsors and Collaborators

• Bausch Health Americas, Inc.

Investigators

• Study Director: Mandeep Kaur, MD, Valeant Pharmaceutical NA

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Bausch Health Americas, Inc.
• ClinicalTrials.gov Identifier: NCT01007448
• Other Study ID Numbers: E7273-G000-401
• First Posted: Nov 4, 2009
• Last Update Posted: Nov 12, 2019
• Last Verified: Nov 1, 2019

• Keywords provided by Bausch Health Americas, Inc.: CTCL; bexarotene; Targretin; Refractory Cutaneous T-cell Lymphoma; cutaneous T-cell Lymphoma; MF; Mycoses fungoides
• Additional relevant MeSH terms: Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Lymphoma, T-Cell, Cutaneous; Bexarotene

Study Results

Participant Flow

Pre-assignment Detail	Participants were randomized in a 1:1 ratio to bexarotene 150 milligrams (mg)/square meter (m^2)/day or 300 mg/m^2/day.

Arm/Group Title	Bexarotene 150 mg/m^2/Day	Bexarotene 300 mg/m^2/Day
Arm/Group Description	Participants received bexarotene 150 mg/m^2/day once daily for 24 weeks.	Participants received bexarotene 300 mg/m^2/day once daily for 24 weeks.
Period Title: Overall Study
STARTED	30	29
Full Analysis Population	30	29
Safety Population	30	29
COMPLETED	20	20
NOT COMPLETED	10	9

Baseline Characteristics

Arm/Group Title	Bexarotene 150 mg/m^2/Day	Bexarotene 300 mg/m^2/Day	Total
Arm/Group Description	Participants received bexarotene 150 mg/m^2/day once daily for 24 weeks.	Participants received bexarotene 300 mg/m^2/day once daily for 24 weeks.	Total of all reporting groups
Overall Participants	30	29	59
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.2 (14.80)	61.0 (13.94)	60.6 (14.26)
Sex: Female, Male (Count of Participants)
Female	13 43.3%	13 44.8%	26 44.1%
Male	17 56.7%	16 55.2%	33 55.9%

Outcome Measures

1. Primary Outcome

Title	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
Description	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).
Time Frame	Baseline up to Week 24

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of study drug (Full Analysis Population).

Arm/Group Title	Bexarotene 150 mg/m^2/Day	Bexarotene 300 mg/m^2/Day
Arm/Group Description	Participants received bexarotene 150 mg/m^2/day once daily for 24 weeks.	Participants received bexarotene 300 mg/m^2/day once daily for 24 weeks.
Measure Participants	30	29
CR	0 0%	0 0%
CCR	2 6.7%	3 10.3%
PR	5 16.7%	7 24.1%

2. Primary Outcome

Title	Number of Participants With Tumor Response of CR, CCR, PR, SD, and PD as Determined by Physician's Global Assessment (PGA) of Clinical Condition
Description	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.
Time Frame	Baseline up to Week 24

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of study drug (Full Analysis Population).

Arm/Group Title	Bexarotene 150 mg/m^2/Day	Bexarotene 300 mg/m^2/Day
Arm/Group Description	Participants received bexarotene 150 mg/m^2/day once daily for 24 weeks.	Participants received bexarotene 300 mg/m^2/day once daily for 24 weeks.
Measure Participants	30	29
CR	0 0%	0 0%
CCR	1 3.3%	3 10.3%
PR	5 16.7%	8 27.6%
SD	23 76.7%	16 55.2%
PD	0 0%	0 0%
Unknown	1 3.3%	2 6.9%

3. Primary Outcome

Title	Number of Participants With Tumor Response of CR, CCR, PR, SD, and PD as Determined Percent Body Surface Area (BSA) Involvement
Description	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%.
Time Frame	Baseline up to Week 24

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of study drug (Full Analysis Population).

Arm/Group Title	Bexarotene 150 mg/m^2/Day	Bexarotene 300 mg/m^2/Day
Arm/Group Description	Participants received bexarotene 150 mg/m^2/day once daily for 24 weeks.	Participants received bexarotene 300 mg/m^2/day once daily for 24 weeks.
Measure Participants	30	29
CR	1 3.3%	2 6.9%
CCR	0 0%	1 3.4%
PR	6 20%	7 24.1%
SD	22 73.3%	17 58.6%
PD	0 0%	0 0%
Unknown	1 3.3%	2 6.9%

4. Secondary Outcome

Title	Duration of Tumor Response (CR, CCR, or PR) as Determined by Investigator's CA of Index Lesion Disease Severity
Description	Defined as time interval from onset of response to time participant relapses or last date of data collected with an assessment of participant still meeting response criteria. Index lesion symptoms/grade: erythema/scaling=0 (no evidence)-8 (very severe); plaque elevation=0 (no evidence)-8 (extreme elevation); hypopigmentation/hyperpigmentation=0 (no evidence)-8 (very severe change); area of involvement=0 (0 cm^2)-18 (>300 cm^2). CA: sum of signs/symptoms grades for index lesion. Index lesion CA grade at baseline divided into CA grade at study visit to determine treatment response. CA Ratio <1.0=improvement and >1.0=worsening of disease. Tumor response=percentage of participants with CR (CA ratio=0, no clinically abnormal lymph nodes, absence of CTCL histologic signs); CCR (CA ratio=0; no clinically abnormal lymph nodes); PR (CA ratio=≤0.5, <25% increase in number/aggregate area of abnormal lymph nodes/tumors, no new abnormal lymph nodes in documented area of absence of disease).
Time Frame	Baseline up to Week 24

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of study drug (Full Analysis Population) and with the best overall response of evaluable CR, CCR, and PR data for CA of index lesion disease severity.

Arm/Group Title	Bexarotene 150 mg/m^2/Day	Bexarotene 300 mg/m^2/Day
Arm/Group Description	Participants received bexarotene 150 mg/m^2/day once daily for 24 weeks.	Participants received bexarotene 300 mg/m^2/day once daily for 24 weeks.
Measure Participants	7	10
Mean (Standard Deviation) [days]	65.9 (41.86)	83.7 (36.50)

5. Secondary Outcome

Title	Duration of Tumor Response (CR, CCR, or PR) as Determined by PGA of Clinical Condition
Description	Defined as time interval from onset of response to time participant relapses or last date of data collected with an assessment of participant still meeting response criteria. 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).
Time Frame	Baseline up to Week 24

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of study drug (Full Analysis Population) and with the best overall response of evaluable CR, CCR, and PR data for PGA of clinical condition.

Arm/Group Title	Bexarotene 150 mg/m^2/Day	Bexarotene 300 mg/m^2/Day
Arm/Group Description	Participants received bexarotene 150 mg/m^2/day once daily for 24 weeks.	Participants received bexarotene 300 mg/m^2/day once daily for 24 weeks.
Measure Participants	6	11
Mean (Standard Deviation) [days]	111.5 (34.61)	69.4 (38.93)

6. Secondary Outcome

Title	Duration of Tumor Response (CR, CCR, or PR) as Determined by Percent BSA Involvement
Description	Defined as time interval from onset of response to time participant relapses or last date of data collected with an assessment of participant still meeting response criteria. To determine BSA, 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%.
Time Frame	Baseline up to Week 24

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of study drug (Full Analysis Population) and with the best overall response of evaluable CR, CCR, and PR data for percent of BSA involvement.

Arm/Group Title	Bexarotene 150 mg/m^2/Day	Bexarotene 300 mg/m^2/Day
Arm/Group Description	Participants received bexarotene 150 mg/m^2/day once daily for 24 weeks.	Participants received bexarotene 300 mg/m^2/day once daily for 24 weeks.
Measure Participants	7	10
Mean (Standard Deviation) [days]	99.4 (41.69)	54.1 (42.18)

7. Secondary Outcome

Title	Time to Tumor Response (CR, CCR, or PR) as Determined by CA of Index Lesion Disease Severity
Description	Defined as time interval from first day of bexarotene treatment to time of first observation when participant met the criteria of CR, CCR, or PR. Index lesion symptoms/grade: erythema/scaling=0 (no evidence)-8 (very severe); plaque elevation=0 (no evidence)-8 (extreme elevation); hypopigmentation/hyperpigmentation=0 (no evidence)-8 (very severe change); and area of involvement=0 (0 cm^2)-18 (>300 cm^2). CA: sum of signs/symptoms grades for index lesion. Index lesion CA grade at baseline divided into CA grade at study visit to determine treatment response. CA Ratio <1.0=improvement and >1.0=worsening of disease. Tumor response=percentage of participants with CR (CA ratio=0, no clinically abnormal lymph nodes, and absence of CTCL histologic signs); 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).
Time Frame	Baseline up to Week 24

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of study drug (Full Analysis Population) and with the best overall response of evaluable CR, CCR, and PR data for CA of index lesion disease severity.

Arm/Group Title	Bexarotene 150 mg/m^2/Day	Bexarotene 300 mg/m^2/Day
Arm/Group Description	Participants received bexarotene 150 mg/m^2/day once daily for 24 weeks.	Participants received bexarotene 300 mg/m^2/day once daily for 24 weeks.
Measure Participants	7	10
Mean (Standard Deviation) [days]	99.9 (39.14)	91.6 (37.20)

8. Secondary Outcome

Title	Time to Tumor Response (CR, CCR, or PR) as Determined by PGA of Clinical Condition
Description	Defined as time interval from first day of bexarotene treatment to time of first observation when participant met the criteria of CR, CCR, or PR. 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).
Time Frame	Baseline up to Week 24

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of study drug (Full Analysis Population) and with the best overall response of evaluable CR, CCR, and PR data for PGA of clinical condition.

Arm/Group Title	Bexarotene 150 mg/m^2/Day	Bexarotene 300 mg/m^2/Day
Arm/Group Description	Participants received bexarotene 150 mg/m^2/day once daily for 24 weeks.	Participants received bexarotene 300 mg/m^2/day once daily for 24 weeks.
Measure Participants	6	11
Mean (Standard Deviation) [days]	53.5 (23.32)	103.5 (41.34)

9. Secondary Outcome

Title	Time to Tumor Response (CR, CCR, or PR) as Determined by Percent BSA Involvement
Description	Defined as time interval from first day of bexarotene treatment to time of first observation when participant met the criteria of CR, CCR, or PR. To determine BSA, 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%.
Time Frame	Baseline up to Week 24

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of study drug (Full Analysis Population) and with the best overall response of evaluable CR, CCR, and PR data for percent of BSA involvement.

Arm/Group Title	Bexarotene 150 mg/m^2/Day	Bexarotene 300 mg/m^2/Day
Arm/Group Description	Participants received bexarotene 150 mg/m^2/day once daily for 24 weeks.	Participants received bexarotene 300 mg/m^2/day once daily for 24 weeks.
Measure Participants	7	10
Mean (Standard Deviation) [days]	66.1 (36.97)	117.0 (41.90)

10. Secondary Outcome

Title	Time to Tumor Progression as Determined by CA of Index Lesion Disease Severity
Description	Defined as time interval from first day of bexarotene treatment to time of first observation when participant met criteria for PD. Index lesion symptoms/grade: erythema/scaling=0 (no evidence)-8 (very severe); plaque elevation=0 (no evidence)-8 (extreme elevation); hypopigmentation/hyperpigmentation=0 (no evidence)-8 (very severe change); and area of involvement=0 (0 cm^2)-18 (>300 cm^2). CA: sum of signs/symptoms grades for index lesion. Index lesion CA grade at baseline divided into CA grade at study visit to determine treatment response. CA Ratio <1.0=improvement and >1.0=worsening of disease. Criteria for PD requires at least 1 component of the following: CA ratio=≥1.25, ≥25% increase in number/aggregate area of abnormal lymph nodes/tumors, or no new abnormal lymph nodes in documented area of absence of disease.
Time Frame	Baseline up to Week 24

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of study drug (Full Analysis Population) and with evaluable PD data for CA of index lesion disease severity.

Arm/Group Title	Bexarotene 150 mg/m^2/Day	Bexarotene 300 mg/m^2/Day
Arm/Group Description	Participants received bexarotene 150 mg/m^2/day once daily for 24 weeks.	Participants received bexarotene 300 mg/m^2/day once daily for 24 weeks.
Measure Participants	1	2
Mean (Standard Deviation) [days]	203.0 (NA)	77.5 (58.69)

11. Secondary Outcome

Title	Time to Tumor Progression as Determined by PGA of Clinical Condition
Description	Defined as time interval from first day of bexarotene treatment to time of first observation when participant met criteria for PD. 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. 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.
Time Frame	Baseline up to Week 24

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of study drug (Full Analysis Population) and with progression.

Arm/Group Title	Bexarotene 150 mg/m^2/Day	Bexarotene 300 mg/m^2/Day
Arm/Group Description	Participants received bexarotene 150 mg/m^2/day once daily for 24 weeks.	Participants received bexarotene 300 mg/m^2/day once daily for 24 weeks.
Measure Participants	0	2
Mean (Standard Deviation) [days]	115.5 (4.95)

12. Secondary Outcome

Title	Time to Tumor Progression as Determined by Percent BSA Involvement
Description	Defined as time interval from first day of bexarotene treatment to time of first observation when participant met criteria for PD. 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. PD=an increase from Baseline in percent BSA of at least 25%.
Time Frame	Baseline up to Week 24

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of study drug (Full Analysis Population) and with progression.

Arm/Group Title	Bexarotene 150 mg/m^2/Day	Bexarotene 300 mg/m^2/Day
Arm/Group Description	Participants received bexarotene 150 mg/m^2/day once daily for 24 weeks.	Participants received bexarotene 300 mg/m^2/day once daily for 24 weeks.
Measure Participants	2	2
Mean (Standard Deviation) [days]	86.0 (1.41)	88.0 (43.84)

Adverse Events

Time Frame	Baseline up to Week 28
Adverse Event Reporting Description	Received at Least 1 Dose of Study Drug and had at least 1 safety assessment after treatment (Safety Population).
Arm/Group Title	Bexarotene 150 mg/m^2/Day		Bexarotene 300 mg/m^2/Day
Arm/Group Description	Participants received bexarotene 150 mg/m^2/day once daily for 24 weeks.		Participants received bexarotene 300 mg/m^2/day once daily for 24 weeks.
All Cause Mortality
	Bexarotene 150 mg/m^2/Day		Bexarotene 300 mg/m^2/Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Bexarotene 150 mg/m^2/Day		Bexarotene 300 mg/m^2/Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/30 (36.7%)		13/29 (44.8%)
Blood and lymphatic system disorders
Bone marrow failure	1/30 (3.3%)		3/29 (10.3%)
Neutropenia	0/30 (0%)		3/29 (10.3%)
Anaemia	0/30 (0%)		1/29 (3.4%)
Cardiac disorders
Cardiac failure congestive	1/30 (3.3%)		0/29 (0%)
Atrioventricular block first degree	1/30 (3.3%)		0/29 (0%)
Endocrine disorders
Hypothyroidism	1/30 (3.3%)		0/29 (0%)
Gastrointestinal disorders
Abdominal pain upper	0/30 (0%)		1/29 (3.4%)
General disorders
Chest pain	1/30 (3.3%)		0/29 (0%)
Oedema peripheral	1/30 (3.3%)		0/29 (0%)
Hepatobiliary disorders
Cholecystitis	1/30 (3.3%)		0/29 (0%)
Infections and infestations
Pneumonia	0/30 (0%)		2/29 (6.9%)
Injury, poisoning and procedural complications
Lumbar vertebral fracture	1/30 (3.3%)		0/29 (0%)
Investigations
Blood triglycerides increased	1/30 (3.3%)		0/29 (0%)
Metabolism and nutrition disorders
Hypercholesterolaemia	0/30 (0%)		1/29 (3.4%)
Hypertriglyceridaemia	2/30 (6.7%)		9/29 (31%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Mycosis fungoides	0/30 (0%)		1/29 (3.4%)
Nervous system disorders
Syncope	1/30 (3.3%)		0/29 (0%)
Renal and urinary disorders
Renal failure	1/30 (3.3%)		0/29 (0%)
Hydronephrosis	1/30 (3.3%)		0/29 (0%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	0/30 (0%)		1/29 (3.4%)
Vascular disorders
Peripheral vascular disorder	1/30 (3.3%)		0/29 (0%)
Other (Not Including Serious) Adverse Events
	Bexarotene 150 mg/m^2/Day		Bexarotene 300 mg/m^2/Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/30 (70%)		21/29 (72.4%)
Blood and lymphatic system disorders
Neutropenia	2/30 (6.7%)		5/29 (17.2%)
Bone marrow failure	1/30 (3.3%)		3/29 (10.3%)
Endocrine disorders
Hypothyroidism	12/30 (40%)		15/29 (51.7%)
Gastrointestinal disorders
Diarrhea	2/30 (6.7%)		3/29 (10.3%)
Nausea	1/30 (3.3%)		2/29 (6.9%)
Constipation	0/30 (0%)		2/29 (6.9%)
General disorders
Oedema peripheral	2/30 (6.7%)		4/29 (13.8%)
Fatigue	2/30 (6.7%)		2/29 (6.9%)
Infections and infestations
Urinary tract infection	3/30 (10%)		1/29 (3.4%)
Sinusitis	2/30 (6.7%)		1/29 (3.4%)
Upper respiratory tract infection	2/30 (6.7%)		1/29 (3.4%)
Nasopharyngitis	2/30 (6.7%)		0/29 (0%)
Pnemonia	0/30 (0%)		2/29 (6.9%)
Investigations
Blood triglycerides increased	3/30 (10%)		4/29 (13.8%)
Thyroxine free decreased	4/30 (13.3%)		4/29 (13.8%)
Alanine aminotransferase increased	3/30 (10%)		4/29 (13.8%)
Bacterial test positive	4/30 (13.3%)		1/29 (3.4%)
White blood cell count decreased	2/30 (6.7%)		2/29 (6.9%)
Neutrophil count decreased	3/30 (10%)		0/29 (0%)
Aspartate aminotransferase increased	3/30 (10%)		4/29 (13.8%)
Metabolism and nutrition disorders
Hypertriglyceridemia	17/30 (56.7%)		14/29 (48.3%)
Hypercholesterolemia	7/30 (23.3%)		7/29 (24.1%)
Dehydration	0/30 (0%)		2/29 (6.9%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/30 (6.7%)		3/29 (10.3%)
Muscle spasms	1/30 (3.3%)		2/29 (6.9%)
Hypercreatinaemia	2/30 (6.7%)		0/29 (0%)
Osteopenia	0/30 (0%)		2/29 (6.9%)
Osteoporosis	2/30 (6.7%)		0/29 (0%)
Pain in extremity	0/30 (0%)		2/29 (6.9%)
Musculoskeletal pain	0/30 (0%)		2/29 (6.9%)
Nervous system disorders
Headache	7/30 (23.3%)		9/29 (31%)
Lethargy	2/30 (6.7%)		0/29 (0%)
Psychiatric disorders
Insomnia	0/30 (0%)		2/29 (6.9%)
Renal and urinary disorders
Pollakiuria	0/30 (0%)		2/29 (6.9%)
Proteinuria	2/30 (6.7%)		0/29 (0%)
Skin and subcutaneous tissue disorders
Skin exfoliation	5/30 (16.7%)		5/29 (17.2%)
Vascular disorders
Hypertension	2/30 (6.7%)		1/29 (3.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Please contact Sponsor directly for additional information.