Cutaneous T-Cell Lymphoma
Conditions
Keywords
Cutaneous T-Cell Lymphoma, adults, Mycosis Fungoides, Sézary Syndrome, CTCL
Brief summary
This study will evaluate the safety and efficacy of LBH489B in adult patients with refractory Cutaneous T-Cell Lymphoma.
Interventions
DRUGPanobinostat
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Written informed consent obtained prior to any screening procedures 2. Age ≥ 18 years old 3. Patients with biopsy-confirmed stages IB-IVA mycosis fungoides or Sézary syndrome. Patients with SS who have bone marrow involvement are also eligible. 4. Patients must have received at least two prior treatment regimens at least one of which was a systemic therapy regimen. Systemic regimens include oral bexarotene, PUVA, photophoresis, oral corticosteroids, total skin electron bean therapy, chemotherapy such as methotrexate, and interferon. Topical steroids alone are not considered as a treatment regimen. 5. Patients must have had disease progression on or following their most recent treatment regimen or an inadequate response to their most recent treatment regimen. 6. Patients will be accrued to one of two groups: Patients previously treated with oral bexarotene and patients who have not had prior oral bexarotene treatment.
Exclusion criteria
1. Prior treatment with an HDAC inhibitor. 2. Patients with visceral disease including CNS involvement (i.e. stage IVB CTCL). Note; Patients with SS who have bone marrow involvement are eligible. 3. Impaired cardiac function 4. Concomitant use of drugs with a risk of causing torsades de pointes 5. Patients who have received chemotherapy or any investigational drug or undergone major surgery \< 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy 6. Less than 3 months since prior electron beam therapy 7. Female patients who are pregnant or breast feeding, or patients of reproductive potential not using an effective method of birth control, and male patients whose sexual partners are women of childbearing potential not using effective birth control 8. Uncontrolled hypertension 9. Concomitant use of any anti-cancer therapy or radiation therapy. Low potency topical steroid use is permitted. Topical bexarotene use is prohibited during the trial 10. Concomitant use of CYP3A4/5 inhibitors. 11. Patients with unresolved diarrhea \> CTCAE grade 1 12. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral LBH589 13. Other concurrent severe and/or uncontrolled medical conditions 14. Patients who would need to receive valproic acid for any reason during the study or ≤ 5 days prior to starting study drug. Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate of Participants Using the Modified Severity-Weighted Assessment Tool (mSWAT) | Baseline up to 6 Months of Follow up | Skin response was primarily classified based on an assessment using mSWAT, provided there was documented evidence of stable disease or better in lymph node/viscera.The mSWAT is a tool specifically developed to evaluate the extent of skin disease in CTCL (Olsen et al 2007). Responses in the skin based on SWAT are defined as: * Complete Response (CR): no evidence of skin disease * Partial Response (PR): ≥ 50% decrease of the modified SWAT score compared with baseline * Stable Disease (SD): Neither CR, PR, or PD as compared with baseline, i.e. change from baseline is less than a 50% decrease but also less than a 25 % increase in the modified SWAT score * Progressive Disease (PD): ≥ 25% increase in the modified SWAT score compared with baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Response for Responders | Baseline up to Cycle 12, an average of 12 months | Time to response were summarized. A Kaplan-Meier analysis of time to progression was performed, including estimation and 95% confidence interval of the median time to progression and progression-free survival. |
| Duration of Response (DOS) | Baseline up to Cycle 12, an average of 12 months | Duration of response and time to response were summarized. A Kaplan-Meier analysis of time to progression was performed, including estimation and 95% confidence interval of the median time to progression and progression-free survival. |
| Progression-free Survival (PFS) | Baseline up to Cycle 12, an average of 12 months | PFS is defined as time from first dose of study treatment to progression or death due to any cause, based on modified European Society for Bone and Marrow Transplantation (EBMT) criteria per Investigator's assessment |
| Skindex-29 Measurements of Average Sub-scores for Emotions From Baseline up to Cycle 12 | Baseline up to Cycle 12, an average of 12 months | Skin index measurement (Skindex-29) was a self-administered 29-item dermatology patient-reported outcome measure that explores the domains of Functioning, Emotions and Symptoms. Data from the Skindex-29 came from the Dermatology Survey page. Scoring of the Skindex-29 was performed as per the developers' scoring algorithms. The score for each dimension was found by adding responses of 1 to 5 for each question, with higher scores indicating worse quality of life. The Skindex-29 yields three scale scores that assess emotions scores range from 29 to 116, with higher scores indicating worse health-related quality of life. Average sub-scores for emotions, physical symptoms, and functioning was displayed. |
| Skindex-29 Measurements of Average Sub-scores for Functioning From Baseline up to Cycle 12 | Baseline up to Cycle 12, an average of 12 months | Skindex-29 was a self-administered 29-item dermatology patient-reported outcome measure that explores the domains of Functioning, Emotions and Symptoms. Data from the Skindex-29 came from the Dermatology Survey page. Scoring of the Skindex-29 was performed as per the developers' scoring algorithms. The score for each dimension was found by adding responses of 1 to 5 for each question, with higher scores indicating worse quality of life. The Skindex-29 yields three scale scores that assess functioning scores range from 29 to 116, with higher scores indicating worse health-related quality of life. Average sub-scores for emotions, physical symptoms, and functioning was displayed. |
| The Overall Response Rate Using mSWAT Skin Score | Baseline up to Cycle 12, an average of 12 months | Estimate of the response rate of participants with resistant cutaneous T-cell lymphoma (CTCL) treated with Panobinostat using the mSWAT skin scores and 95% CI will be analyzed. |
| Maximum Plasma Concentration (Cmax) of Panobinostat | Pre-dose, 0.25, 1-2, and 3-4 hours post dose on Day 1 and Day 8 | Cmax is defined as the maximum observed drug concentration observed in plasma over all PK sample concentrations. It will be obtained from the Cmax parameter calculated by WinNonlin®. If there is no measurable concentration in the subject's PK profile, then Cmax will be missing for that subject. Cmax will be reported in units of ng/mL. |
| Time to Peak Concentration (Tmax) of Panobinostat | Pre-dose, 0.25, 1-2, and 3-4 hours post dose on Day 1 and Day 8 | Tmax is defined as the time at which the Cmax occurs. It will be obtained from the Tmax parameter calculated by WinNonlin®. If there is no measurable Cmax in the subject's PK profile, then Tmax will be missing for that subject. Tmax will be reported in units of h. |
| Area Under the Plasma Concentration AUC0-24, AUC0-48 and AUC 0-infinity of Panobinostat | Pre-dose, 0.25, 1-2, and 3-4 hours post dose on Day 1 and Day 8 | AUC is defined as the area under concentration-time curve as a measure of drug exposure. The area under the plasma concentration-time curve from time zero to 24 hours. The area under the plasma concentration-time curve from time zero to 48 hours. AUC (0-inf) is defined as the area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time. |
| Time of Clast (Tlast) of Panobinostat | Pre-dose, 0.25, 1-2, and 3-4 hours post dose on Day 1 and Day 8 | Time of Clast (Tlast) will be obtained from the Tlast parameter calculated by WinNonlin®. If there is no measurable concentration in the subject's PK profile, then Tlast will be missing for that participants. Tlast will be reported in units of h. |
| Last Observed Plasma Concentration (Clast) of Panobinostat | Pre-dose, 0.25, 1-2, and 3-4 hours post dose on Day 1 and Day 8 | Clast is defined as the Last observed (quantifiable) plasma concentration (Clast), in units of ng/mL. Blood samples were collected to assess Clast. |
| Skindex-29 Measurements of Average Sub-scores for Physical Symptoms From Baseline up to Cycle 12 | Baseline up to Cycle 12, an average of 12 months | Skindex-29 was a self-administered 29-item dermatology patient-reported outcome measure that explores the domains of Functioning, Emotions and Symptoms. Data from the Skindex-29 came from the Dermatology Survey page. Scoring of the Skindex-29 was performed as per the developers' scoring algorithms. The score for each dimension was found by adding responses of 1 to 5 for each question, with higher scores indicating worse quality of life. The Skindex-29 yields three scale scores that assess physical symptoms scores range from 29 to 116, with higher scores indicating worse health-related quality of life. Average sub-scores for emotions, physical symptoms, and functioning was displayed. |
Countries
Argentina, Australia, Belgium, Canada, Finland, France, Germany, Hungary, Italy, Spain, Switzerland, United States
Participant flow
Recruitment details
The study was conducted at 41 centers in 12 countries.
Pre-assignment details
A total 139 Participants were enrolled in the Study. No Patients completed treatment. All patients discontinued the treatment on this study and 136 patients discontinued the study (97.8%). The remaining three patients discontinued the study treatment were immediately transferred to another program.
Participants by arm
| Arm | Count |
|---|---|
| Bexarotene Exposed Participants received Panobinostat 20 mg/day capsule orally, OD on 3 days per week. (Monday, Wednesday and Friday or alternative Day 1, 3 and 5). The treatment duration was not fixed. Participants continued treatment until disease progression or unacceptable toxicity occurred. | 79 |
| Bexarotene Naive Participants received Panobinostat 20 mg/day capsule orally, OD on 3 days per week. (Monday, Wednesday and Friday or alternative Day 1, 3 and 5). The treatment duration was not fixed. Participants continued treatment until disease progression or unacceptable toxicity occurred. | 60 |
| Total | 139 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative problems | 3 | 0 |
| Overall Study | Adverse Event | 25 | 15 |
| Overall Study | Death | 1 | 2 |
| Overall Study | Disease progression | 36 | 33 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | New cancer therapy | 2 | 1 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 11 | 8 |
Baseline characteristics
| Characteristic | Bexarotene Naive | Bexarotene Exposed | Total |
|---|---|---|---|
| Age, Continuous | 62.1 years STANDARD_DEVIATION 11.51 | 57.9 years STANDARD_DEVIATION 14.7 | 59.7 years STANDARD_DEVIATION 13.53 |
| Race/Ethnicity, Customized Asian | 1 Participants | 3 Participants | 4 Participants |
| Race/Ethnicity, Customized Black | 3 Participants | 3 Participants | 6 Participants |
| Race/Ethnicity, Customized Caucasian | 54 Participants | 68 Participants | 122 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 5 Participants | 7 Participants |
| Sex: Female, Male Female | 19 Participants | 32 Participants | 51 Participants |
| Sex: Female, Male Male | 41 Participants | 47 Participants | 88 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 79 | 3 / 60 |
| other Total, other adverse events | 77 / 79 | 59 / 60 |
| serious Total, serious adverse events | 33 / 79 | 23 / 60 |
Outcome results
Primary
Overall Response Rate of Participants Using the Modified Severity-Weighted Assessment Tool (mSWAT)
Skin response was primarily classified based on an assessment using mSWAT, provided there was documented evidence of stable disease or better in lymph node/viscera.The mSWAT is a tool specifically developed to evaluate the extent of skin disease in CTCL (Olsen et al 2007). Responses in the skin based on SWAT are defined as: * Complete Response (CR): no evidence of skin disease * Partial Response (PR): ≥ 50% decrease of the modified SWAT score compared with baseline * Stable Disease (SD): Neither CR, PR, or PD as compared with baseline, i.e. change from baseline is less than a 50% decrease but also less than a 25 % increase in the modified SWAT score * Progressive Disease (PD): ≥ 25% increase in the modified SWAT score compared with baseline.
Time frame: Baseline up to 6 Months of Follow up
Population: The analysis was performed in Full Analysis Set (FAS) population was defined according to the intention-to-treat principle. This population will include all participants enrolled into the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bexarotene Exposed | Overall Response Rate of Participants Using the Modified Severity-Weighted Assessment Tool (mSWAT) | 16.7 percentage |
| Bexarotene Naive | Overall Response Rate of Participants Using the Modified Severity-Weighted Assessment Tool (mSWAT) | 20.3 percentage |
| All Participants | Overall Response Rate of Participants Using the Modified Severity-Weighted Assessment Tool (mSWAT) | 18.5 percentage |
Secondary
Area Under the Plasma Concentration AUC0-24, AUC0-48 and AUC 0-infinity of Panobinostat
AUC is defined as the area under concentration-time curve as a measure of drug exposure. The area under the plasma concentration-time curve from time zero to 24 hours. The area under the plasma concentration-time curve from time zero to 48 hours. AUC (0-inf) is defined as the area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time.
Time frame: Pre-dose, 0.25, 1-2, and 3-4 hours post dose on Day 1 and Day 8
Population: The analysis was performed in PAS population, defined as all participants who provide at least one post-dose PK plasma sample. Here, number of participants analyzed refer to the number of participants evaluable for this outcome at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bexarotene Exposed | Area Under the Plasma Concentration AUC0-24, AUC0-48 and AUC 0-infinity of Panobinostat | Day 8 - AUC (0-inf) | 162.673 ng*hr/ml | Standard Deviation 65.0664 |
| Bexarotene Exposed | Area Under the Plasma Concentration AUC0-24, AUC0-48 and AUC 0-infinity of Panobinostat | Day 1 - AUC0-24 | 110.138 ng*hr/ml | Standard Deviation 58.0235 |
| Bexarotene Exposed | Area Under the Plasma Concentration AUC0-24, AUC0-48 and AUC 0-infinity of Panobinostat | Day 8 - AUC0-24 | 134.033 ng*hr/ml | Standard Deviation 61.5203 |
| Bexarotene Exposed | Area Under the Plasma Concentration AUC0-24, AUC0-48 and AUC 0-infinity of Panobinostat | Day 1 - AUC0-48 | 132.019 ng*hr/ml | Standard Deviation 69.3453 |
| Bexarotene Exposed | Area Under the Plasma Concentration AUC0-24, AUC0-48 and AUC 0-infinity of Panobinostat | Day 8 - AUC0-48 | 159.750 ng*hr/ml | Standard Deviation 64.2278 |
| Bexarotene Exposed | Area Under the Plasma Concentration AUC0-24, AUC0-48 and AUC 0-infinity of Panobinostat | Day 1- AUC (0-inf) | 134.828 ng*hr/ml | Standard Deviation 64.9389 |
Secondary
Duration of Response (DOS)
Duration of response and time to response were summarized. A Kaplan-Meier analysis of time to progression was performed, including estimation and 95% confidence interval of the median time to progression and progression-free survival.
Time frame: Baseline up to Cycle 12, an average of 12 months
Population: The analysis was performed in FAS population was defined according to the intention-to-treat principle. This population will include all participants enrolled into the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bexarotene Exposed | Duration of Response (DOS) | 170.0 Days |
| Bexarotene Naive | Duration of Response (DOS) | NA Days |
| All Participants | Duration of Response (DOS) | 280.0 Days |
Secondary
Last Observed Plasma Concentration (Clast) of Panobinostat
Clast is defined as the Last observed (quantifiable) plasma concentration (Clast), in units of ng/mL. Blood samples were collected to assess Clast.
Time frame: Pre-dose, 0.25, 1-2, and 3-4 hours post dose on Day 1 and Day 8
Population: The analysis was performed in PAS population, defined as all participants who provide at least one post-dose PK plasma sample. Here, number of participants analyzed refer to the number of participants evaluable for this outcome at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bexarotene Exposed | Last Observed Plasma Concentration (Clast) of Panobinostat | Day 1 | 0.632 ng/mL | Standard Deviation 0.9737 |
| Bexarotene Exposed | Last Observed Plasma Concentration (Clast) of Panobinostat | Day 8 | 1.524 ng/mL | Standard Deviation 0.9076 |
Secondary
Maximum Plasma Concentration (Cmax) of Panobinostat
Cmax is defined as the maximum observed drug concentration observed in plasma over all PK sample concentrations. It will be obtained from the Cmax parameter calculated by WinNonlin®. If there is no measurable concentration in the subject's PK profile, then Cmax will be missing for that subject. Cmax will be reported in units of ng/mL.
Time frame: Pre-dose, 0.25, 1-2, and 3-4 hours post dose on Day 1 and Day 8
Population: The analysis was performed in PK population, defined as all participants who provide at least one post-dose PK plasma sample. Here, number of participants analyzed refer to the number of participants evaluable for this outcome at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bexarotene Exposed | Maximum Plasma Concentration (Cmax) of Panobinostat | Day 1 | 11.379 ng/mL | Standard Deviation 6.6608 |
| Bexarotene Exposed | Maximum Plasma Concentration (Cmax) of Panobinostat | Day 8 | 13.490 ng/mL | Standard Deviation 6.4529 |
Secondary
Progression-free Survival (PFS)
PFS is defined as time from first dose of study treatment to progression or death due to any cause, based on modified European Society for Bone and Marrow Transplantation (EBMT) criteria per Investigator's assessment
Time frame: Baseline up to Cycle 12, an average of 12 months
Population: The analysis was performed in FAS population was defined according to the intention-to-treat principle. This population will include all participants enrolled into the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bexarotene Exposed | Progression-free Survival (PFS) | 127.0 months |
| Bexarotene Naive | Progression-free Survival (PFS) | 113.0 months |
| All Participants | Progression-free Survival (PFS) | 114.0 months |
Secondary
Skindex-29 Measurements of Average Sub-scores for Emotions From Baseline up to Cycle 12
Skin index measurement (Skindex-29) was a self-administered 29-item dermatology patient-reported outcome measure that explores the domains of Functioning, Emotions and Symptoms. Data from the Skindex-29 came from the Dermatology Survey page. Scoring of the Skindex-29 was performed as per the developers' scoring algorithms. The score for each dimension was found by adding responses of 1 to 5 for each question, with higher scores indicating worse quality of life. The Skindex-29 yields three scale scores that assess emotions scores range from 29 to 116, with higher scores indicating worse health-related quality of life. Average sub-scores for emotions, physical symptoms, and functioning was displayed.
Time frame: Baseline up to Cycle 12, an average of 12 months
Population: The analysis was performed in FAS population was defined according to the intention-to-treat principle. This population will include all participants enrolled into the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bexarotene Exposed | Skindex-29 Measurements of Average Sub-scores for Emotions From Baseline up to Cycle 12 | Baseline | 52.2 score on a scale | Standard Deviation 22.66 |
| Bexarotene Exposed | Skindex-29 Measurements of Average Sub-scores for Emotions From Baseline up to Cycle 12 | Cycle 3 | 45.9 score on a scale | Standard Deviation 21.53 |
| Bexarotene Exposed | Skindex-29 Measurements of Average Sub-scores for Emotions From Baseline up to Cycle 12 | Cycle 4 | 40.8 score on a scale | Standard Deviation 23.87 |
| Bexarotene Exposed | Skindex-29 Measurements of Average Sub-scores for Emotions From Baseline up to Cycle 12 | Cycle 5 | 35.8 score on a scale | Standard Deviation 22.19 |
| Bexarotene Exposed | Skindex-29 Measurements of Average Sub-scores for Emotions From Baseline up to Cycle 12 | Cycle 6 | 34.5 score on a scale | Standard Deviation 22.72 |
| Bexarotene Exposed | Skindex-29 Measurements of Average Sub-scores for Emotions From Baseline up to Cycle 12 | Cycle 7 | 39.3 score on a scale | Standard Deviation 24.98 |
| Bexarotene Exposed | Skindex-29 Measurements of Average Sub-scores for Emotions From Baseline up to Cycle 12 | Cycle 8 | 39.4 score on a scale | Standard Deviation 20.03 |
| Bexarotene Exposed | Skindex-29 Measurements of Average Sub-scores for Emotions From Baseline up to Cycle 12 | Cycle 9 | 44.6 score on a scale | Standard Deviation 23.09 |
| Bexarotene Exposed | Skindex-29 Measurements of Average Sub-scores for Emotions From Baseline up to Cycle 12 | Cycle 10 | 43.6 score on a scale | Standard Deviation 20.48 |
| Bexarotene Exposed | Skindex-29 Measurements of Average Sub-scores for Emotions From Baseline up to Cycle 12 | Cycle 11 | 48.3 score on a scale | Standard Deviation 20.92 |
| Bexarotene Exposed | Skindex-29 Measurements of Average Sub-scores for Emotions From Baseline up to Cycle 12 | Cycle 12 | 42.0 score on a scale | Standard Deviation 16.8 |
| Bexarotene Exposed | Skindex-29 Measurements of Average Sub-scores for Emotions From Baseline up to Cycle 12 | Cycle 2 | 48.6 score on a scale | Standard Deviation 23.79 |
| Bexarotene Naive | Skindex-29 Measurements of Average Sub-scores for Emotions From Baseline up to Cycle 12 | Cycle 12 | 43.1 score on a scale | Standard Deviation 21.29 |
| Bexarotene Naive | Skindex-29 Measurements of Average Sub-scores for Emotions From Baseline up to Cycle 12 | Baseline | 50.6 score on a scale | Standard Deviation 22.26 |
| Bexarotene Naive | Skindex-29 Measurements of Average Sub-scores for Emotions From Baseline up to Cycle 12 | Cycle 2 | 46.6 score on a scale | Standard Deviation 24.18 |
| Bexarotene Naive | Skindex-29 Measurements of Average Sub-scores for Emotions From Baseline up to Cycle 12 | Cycle 9 | 32.8 score on a scale | Standard Deviation 18.36 |
| Bexarotene Naive | Skindex-29 Measurements of Average Sub-scores for Emotions From Baseline up to Cycle 12 | Cycle 3 | 44.1 score on a scale | Standard Deviation 24.37 |
| Bexarotene Naive | Skindex-29 Measurements of Average Sub-scores for Emotions From Baseline up to Cycle 12 | Cycle 7 | 36.8 score on a scale | Standard Deviation 22.61 |
| Bexarotene Naive | Skindex-29 Measurements of Average Sub-scores for Emotions From Baseline up to Cycle 12 | Cycle 10 | 43.5 score on a scale | Standard Deviation 24.1 |
| Bexarotene Naive | Skindex-29 Measurements of Average Sub-scores for Emotions From Baseline up to Cycle 12 | Cycle 4 | 34.7 score on a scale | Standard Deviation 21.59 |
| Bexarotene Naive | Skindex-29 Measurements of Average Sub-scores for Emotions From Baseline up to Cycle 12 | Cycle 6 | 35.4 score on a scale | Standard Deviation 20.74 |
| Bexarotene Naive | Skindex-29 Measurements of Average Sub-scores for Emotions From Baseline up to Cycle 12 | Cycle 11 | 43.5 score on a scale | Standard Deviation 22.86 |
| Bexarotene Naive | Skindex-29 Measurements of Average Sub-scores for Emotions From Baseline up to Cycle 12 | Cycle 5 | 34.4 score on a scale | Standard Deviation 20.53 |
| Bexarotene Naive | Skindex-29 Measurements of Average Sub-scores for Emotions From Baseline up to Cycle 12 | Cycle 8 | 35.8 score on a scale | Standard Deviation 22.39 |
Secondary
Skindex-29 Measurements of Average Sub-scores for Functioning From Baseline up to Cycle 12
Skindex-29 was a self-administered 29-item dermatology patient-reported outcome measure that explores the domains of Functioning, Emotions and Symptoms. Data from the Skindex-29 came from the Dermatology Survey page. Scoring of the Skindex-29 was performed as per the developers' scoring algorithms. The score for each dimension was found by adding responses of 1 to 5 for each question, with higher scores indicating worse quality of life. The Skindex-29 yields three scale scores that assess functioning scores range from 29 to 116, with higher scores indicating worse health-related quality of life. Average sub-scores for emotions, physical symptoms, and functioning was displayed.
Time frame: Baseline up to Cycle 12, an average of 12 months
Population: The analysis was performed in FAS population was defined according to the intention-to-treat principle. This population will include all participants enrolled into the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bexarotene Exposed | Skindex-29 Measurements of Average Sub-scores for Functioning From Baseline up to Cycle 12 | Baseline | 46.7 score on a scale | Standard Deviation 24.44 |
| Bexarotene Exposed | Skindex-29 Measurements of Average Sub-scores for Functioning From Baseline up to Cycle 12 | Cycle 2 | 43.5 score on a scale | Standard Deviation 26.27 |
| Bexarotene Exposed | Skindex-29 Measurements of Average Sub-scores for Functioning From Baseline up to Cycle 12 | Cycle 3 | 42.6 score on a scale | Standard Deviation 25.58 |
| Bexarotene Exposed | Skindex-29 Measurements of Average Sub-scores for Functioning From Baseline up to Cycle 12 | Cycle 4 | 38.8 score on a scale | Standard Deviation 25.91 |
| Bexarotene Exposed | Skindex-29 Measurements of Average Sub-scores for Functioning From Baseline up to Cycle 12 | Cycle 5 | 32.8 score on a scale | Standard Deviation 23.35 |
| Bexarotene Exposed | Skindex-29 Measurements of Average Sub-scores for Functioning From Baseline up to Cycle 12 | Cycle 6 | 33.0 score on a scale | Standard Deviation 27.79 |
| Bexarotene Exposed | Skindex-29 Measurements of Average Sub-scores for Functioning From Baseline up to Cycle 12 | Cycle 7 | 33.1 score on a scale | Standard Deviation 26.04 |
| Bexarotene Exposed | Skindex-29 Measurements of Average Sub-scores for Functioning From Baseline up to Cycle 12 | Cycle 8 | 34.4 score on a scale | Standard Deviation 22.73 |
| Bexarotene Exposed | Skindex-29 Measurements of Average Sub-scores for Functioning From Baseline up to Cycle 12 | Cycle 9 | 37.2 score on a scale | Standard Deviation 25.28 |
| Bexarotene Exposed | Skindex-29 Measurements of Average Sub-scores for Functioning From Baseline up to Cycle 12 | Cycle 10 | 35.2 score on a scale | Standard Deviation 25.21 |
| Bexarotene Exposed | Skindex-29 Measurements of Average Sub-scores for Functioning From Baseline up to Cycle 12 | Cycle 11 | 40.0 score on a scale | Standard Deviation 24.47 |
| Bexarotene Exposed | Skindex-29 Measurements of Average Sub-scores for Functioning From Baseline up to Cycle 12 | Cycle 12 | 26.3 score on a scale | Standard Deviation 12.79 |
| Bexarotene Naive | Skindex-29 Measurements of Average Sub-scores for Functioning From Baseline up to Cycle 12 | Cycle 11 | 38.1 score on a scale | Standard Deviation 25.46 |
| Bexarotene Naive | Skindex-29 Measurements of Average Sub-scores for Functioning From Baseline up to Cycle 12 | Baseline | 44.7 score on a scale | Standard Deviation 25.33 |
| Bexarotene Naive | Skindex-29 Measurements of Average Sub-scores for Functioning From Baseline up to Cycle 12 | Cycle 7 | 28.3 score on a scale | Standard Deviation 22.98 |
| Bexarotene Naive | Skindex-29 Measurements of Average Sub-scores for Functioning From Baseline up to Cycle 12 | Cycle 2 | 43.3 score on a scale | Standard Deviation 24.53 |
| Bexarotene Naive | Skindex-29 Measurements of Average Sub-scores for Functioning From Baseline up to Cycle 12 | Cycle 10 | 41.5 score on a scale | Standard Deviation 27.22 |
| Bexarotene Naive | Skindex-29 Measurements of Average Sub-scores for Functioning From Baseline up to Cycle 12 | Cycle 3 | 39.2 score on a scale | Standard Deviation 26.38 |
| Bexarotene Naive | Skindex-29 Measurements of Average Sub-scores for Functioning From Baseline up to Cycle 12 | Cycle 8 | 30.5 score on a scale | Standard Deviation 25.16 |
| Bexarotene Naive | Skindex-29 Measurements of Average Sub-scores for Functioning From Baseline up to Cycle 12 | Cycle 4 | 30.7 score on a scale | Standard Deviation 22.91 |
| Bexarotene Naive | Skindex-29 Measurements of Average Sub-scores for Functioning From Baseline up to Cycle 12 | Cycle 12 | 36.2 score on a scale | Standard Deviation 20.95 |
| Bexarotene Naive | Skindex-29 Measurements of Average Sub-scores for Functioning From Baseline up to Cycle 12 | Cycle 5 | 31.4 score on a scale | Standard Deviation 21.38 |
| Bexarotene Naive | Skindex-29 Measurements of Average Sub-scores for Functioning From Baseline up to Cycle 12 | Cycle 9 | 28.7 score on a scale | Standard Deviation 19.54 |
| Bexarotene Naive | Skindex-29 Measurements of Average Sub-scores for Functioning From Baseline up to Cycle 12 | Cycle 6 | 29.5 score on a scale | Standard Deviation 21.25 |
Secondary
Skindex-29 Measurements of Average Sub-scores for Physical Symptoms From Baseline up to Cycle 12
Skindex-29 was a self-administered 29-item dermatology patient-reported outcome measure that explores the domains of Functioning, Emotions and Symptoms. Data from the Skindex-29 came from the Dermatology Survey page. Scoring of the Skindex-29 was performed as per the developers' scoring algorithms. The score for each dimension was found by adding responses of 1 to 5 for each question, with higher scores indicating worse quality of life. The Skindex-29 yields three scale scores that assess physical symptoms scores range from 29 to 116, with higher scores indicating worse health-related quality of life. Average sub-scores for emotions, physical symptoms, and functioning was displayed.
Time frame: Baseline up to Cycle 12, an average of 12 months
Population: The analysis was performed in FAS population was defined according to the intention-to-treat principle. This population included all participants enrolled into the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bexarotene Exposed | Skindex-29 Measurements of Average Sub-scores for Physical Symptoms From Baseline up to Cycle 12 | Baseline | 60.1 score on a scale | Standard Deviation 19.03 |
| Bexarotene Exposed | Skindex-29 Measurements of Average Sub-scores for Physical Symptoms From Baseline up to Cycle 12 | Cycle 2 | 51.4 score on a scale | Standard Deviation 23.1 |
| Bexarotene Exposed | Skindex-29 Measurements of Average Sub-scores for Physical Symptoms From Baseline up to Cycle 12 | Cycle 3 | 51.1 score on a scale | Standard Deviation 21.92 |
| Bexarotene Exposed | Skindex-29 Measurements of Average Sub-scores for Physical Symptoms From Baseline up to Cycle 12 | Cycle 4 | 47.3 score on a scale | Standard Deviation 22.16 |
| Bexarotene Exposed | Skindex-29 Measurements of Average Sub-scores for Physical Symptoms From Baseline up to Cycle 12 | Cycle 5 | 43.2 score on a scale | Standard Deviation 23.96 |
| Bexarotene Exposed | Skindex-29 Measurements of Average Sub-scores for Physical Symptoms From Baseline up to Cycle 12 | Cycle 6 | 43.5 score on a scale | Standard Deviation 24.72 |
| Bexarotene Exposed | Skindex-29 Measurements of Average Sub-scores for Physical Symptoms From Baseline up to Cycle 12 | Cycle 7 | 45.5 score on a scale | Standard Deviation 23.67 |
| Bexarotene Exposed | Skindex-29 Measurements of Average Sub-scores for Physical Symptoms From Baseline up to Cycle 12 | Cycle 8 | 42.7 score on a scale | Standard Deviation 21.45 |
| Bexarotene Exposed | Skindex-29 Measurements of Average Sub-scores for Physical Symptoms From Baseline up to Cycle 12 | Cycle 9 | 47.1 score on a scale | Standard Deviation 23.42 |
| Bexarotene Exposed | Skindex-29 Measurements of Average Sub-scores for Physical Symptoms From Baseline up to Cycle 12 | Cycle 10 | 46.8 score on a scale | Standard Deviation 23.11 |
| Bexarotene Exposed | Skindex-29 Measurements of Average Sub-scores for Physical Symptoms From Baseline up to Cycle 12 | Cycle 11 | 46.7 score on a scale | Standard Deviation 22.04 |
| Bexarotene Exposed | Skindex-29 Measurements of Average Sub-scores for Physical Symptoms From Baseline up to Cycle 12 | Cycle 12 | 37.7 score on a scale | Standard Deviation 15.52 |
| Bexarotene Naive | Skindex-29 Measurements of Average Sub-scores for Physical Symptoms From Baseline up to Cycle 12 | Cycle 11 | 48.3 score on a scale | Standard Deviation 19.44 |
| Bexarotene Naive | Skindex-29 Measurements of Average Sub-scores for Physical Symptoms From Baseline up to Cycle 12 | Baseline | 55.3 score on a scale | Standard Deviation 20.35 |
| Bexarotene Naive | Skindex-29 Measurements of Average Sub-scores for Physical Symptoms From Baseline up to Cycle 12 | Cycle 7 | 37.7 score on a scale | Standard Deviation 18.66 |
| Bexarotene Naive | Skindex-29 Measurements of Average Sub-scores for Physical Symptoms From Baseline up to Cycle 12 | Cycle 2 | 47.7 score on a scale | Standard Deviation 20.28 |
| Bexarotene Naive | Skindex-29 Measurements of Average Sub-scores for Physical Symptoms From Baseline up to Cycle 12 | Cycle 10 | 47.0 score on a scale | Standard Deviation 21.17 |
| Bexarotene Naive | Skindex-29 Measurements of Average Sub-scores for Physical Symptoms From Baseline up to Cycle 12 | Cycle 3 | 42.9 score on a scale | Standard Deviation 21.72 |
| Bexarotene Naive | Skindex-29 Measurements of Average Sub-scores for Physical Symptoms From Baseline up to Cycle 12 | Cycle 8 | 36.5 score on a scale | Standard Deviation 19.29 |
| Bexarotene Naive | Skindex-29 Measurements of Average Sub-scores for Physical Symptoms From Baseline up to Cycle 12 | Cycle 4 | 35.2 score on a scale | Standard Deviation 16.66 |
| Bexarotene Naive | Skindex-29 Measurements of Average Sub-scores for Physical Symptoms From Baseline up to Cycle 12 | Cycle 12 | 45.1 score on a scale | Standard Deviation 21.93 |
| Bexarotene Naive | Skindex-29 Measurements of Average Sub-scores for Physical Symptoms From Baseline up to Cycle 12 | Cycle 5 | 35.6 score on a scale | Standard Deviation 18.81 |
| Bexarotene Naive | Skindex-29 Measurements of Average Sub-scores for Physical Symptoms From Baseline up to Cycle 12 | Cycle 9 | 35.9 score on a scale | Standard Deviation 15.79 |
| Bexarotene Naive | Skindex-29 Measurements of Average Sub-scores for Physical Symptoms From Baseline up to Cycle 12 | Cycle 6 | 36.2 score on a scale | Standard Deviation 19.02 |
Secondary
The Overall Response Rate Using mSWAT Skin Score
Estimate of the response rate of participants with resistant cutaneous T-cell lymphoma (CTCL) treated with Panobinostat using the mSWAT skin scores and 95% CI will be analyzed.
Time frame: Baseline up to Cycle 12, an average of 12 months
Population: The analysis was performed in FAS population was defined according to the intention-to-treat principle. This population will include all participants enrolled into the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Bexarotene Exposed | The Overall Response Rate Using mSWAT Skin Score | mSWAT skin response (CR/PR)flare considered as disease progression ( f.i.p ) - Number of responders | 12 Participants |
| Bexarotene Exposed | The Overall Response Rate Using mSWAT Skin Score | Physician's Global Assessment- Responder (CR/PR) | 15 Participants |
| Bexarotene Naive | The Overall Response Rate Using mSWAT Skin Score | mSWAT skin response (CR/PR)flare considered as disease progression ( f.i.p ) - Number of responders | 14 Participants |
| Bexarotene Naive | The Overall Response Rate Using mSWAT Skin Score | Physician's Global Assessment- Responder (CR/PR) | 18 Participants |
| All Participants | The Overall Response Rate Using mSWAT Skin Score | mSWAT skin response (CR/PR)flare considered as disease progression ( f.i.p ) - Number of responders | 26 Participants |
| All Participants | The Overall Response Rate Using mSWAT Skin Score | Physician's Global Assessment- Responder (CR/PR) | 33 Participants |
Secondary
Time of Clast (Tlast) of Panobinostat
Time of Clast (Tlast) will be obtained from the Tlast parameter calculated by WinNonlin®. If there is no measurable concentration in the subject's PK profile, then Tlast will be missing for that participants. Tlast will be reported in units of h.
Time frame: Pre-dose, 0.25, 1-2, and 3-4 hours post dose on Day 1 and Day 8
Population: The analysis was performed in PAS population, defined as all participants who provide at least one post-dose PK plasma sample. Here, number of participants analyzed refer to the number of participants evaluable for this outcome at specified time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Bexarotene Exposed | Time of Clast (Tlast) of Panobinostat | Day 1 | 47.9 Hours |
| Bexarotene Exposed | Time of Clast (Tlast) of Panobinostat | Day 8 | NA Hours |
Secondary
Time to Peak Concentration (Tmax) of Panobinostat
Tmax is defined as the time at which the Cmax occurs. It will be obtained from the Tmax parameter calculated by WinNonlin®. If there is no measurable Cmax in the subject's PK profile, then Tmax will be missing for that subject. Tmax will be reported in units of h.
Time frame: Pre-dose, 0.25, 1-2, and 3-4 hours post dose on Day 1 and Day 8
Population: The analysis was performed in PAS population, defined as all participants who provide at least one post-dose PK plasma sample. Here, number of participants analyzed refer to the number of participants evaluable for this outcome at specified time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Bexarotene Exposed | Time to Peak Concentration (Tmax) of Panobinostat | Day 1 | 1.5 h (hours) |
| Bexarotene Exposed | Time to Peak Concentration (Tmax) of Panobinostat | Day 8 | 1.5 h (hours) |
Secondary
Time to Response for Responders
Time to response were summarized. A Kaplan-Meier analysis of time to progression was performed, including estimation and 95% confidence interval of the median time to progression and progression-free survival.
Time frame: Baseline up to Cycle 12, an average of 12 months
Population: The analysis was performed in FAS population was defined according to the intention-to-treat principle. This population will include all participants enrolled into the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bexarotene Exposed | Time to Response for Responders | 69.5 Days |
| Bexarotene Naive | Time to Response for Responders | 85.5 Days |
| All Participants | Time to Response for Responders | 82.0 Days |