Cutaneous T-Cell Lymphoma
Conditions
Keywords
Cutaneous T-Cell Lymphoma, adults, Mycosis Fungoides, Sézary Syndrome, CTCL
Brief summary
This study evaluated the safety and efficacy of LBH589B in adult participants with refractory/resistant Cutaneous T-Cell Lymphoma and prior Histone Deacetylase (HDAC) inhibitor therapy.
Interventions
DRUGPanobinostat
Panobinostat, 20 mg, hard gelatin capsules, orally, thrice weekly.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
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 greater than or equal to 18 years old 3. Participants with biopsy-confirmed stages IB-IVA mycosis fungoides or Sézary syndrome (SS). Participants with SS who have bone marrow involvement are also eligible. Participants with transformed CTCL are eligible 4. Participants must have been treated with an HDAC inhibitor given for the treatment of CTCL. Participants must have had disease progression on or following treatment with an HDAC inhibitor. Participants are also eligible if they had an inadequate response to an HDAC inhibitor defined as stable disease as the best response after at least 3 months of therapy. Participants previously treated with an HDAC inhibitor are also eligible if they experienced intolerance due to adverse events. 5. Baseline multiple-gated acquisition scan (MUGA) or echocardiogram must have demonstrated left ventricular ejection fraction (LVEF) ≥ the lower limit of the institutional normal 6. ECOG performance status ≤ 2
Exclusion criteria
1. Participants with a history of visceral disease including central nervous system (CNS) involvement (i.e. stage IVB CTCL). Note, participants who have SS with bone marrow involvement are eligible 2. Impaired cardiac function 3. Concomitant use of drugs with a risk of causing torsades de pointes 4. Participants who have received chemotherapy or any investigational drug or undergone major surgery ≤ 3 weeks prior to starting study drug or who have not recovered from side effects of such therapy 5. Less than 3 months since prior electron beam therapy 6. Women who are pregnant or breast feeding, or women of childbearing potential (WOCBP) not willing to use a double method of contraception during the study and 3 months after the end of treatment. Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) in Participants With Resistant Cutaneous T-Cell Lymphoma (CTCL) Treated With Oral Panobinostat by Using the Modified Severity-Weighted Assessment Tool (mSWAT) | From first dose of study drug up to disease progression or death, (up to approximately 2 years) | ORR was defined as the percentage of participants with best overall response (OR) of complete response (CR) or partial response (PR) based on mSWAT score, (OR = CR + PR). mSWAT score represents the product of the percentage total body surface area (%TBSA) involvement of each lesion type (patch, plaque, and tumor or ulceration), multiplied by a weighting factor: modified SWAT score = (patch %TBSA x 1) + (plaque %TBSA x 2) + (tumor or ulcer %TBSA x 4). The sum of these 3 numbers gave the modified SWAT score, on a 0 (no lesions) to 400 (lesions covering all areas) scale. CR based on mSWAT score was defined as the absence of skin disease. PR was defined as ≥ 50% decrease of the modified SWAT score compared to the Baseline score. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate in Participants With Refractory CTCL Using Modified Skin Score | From first dose of study drug up to disease progression or death, (up to approximately 2 years) | Response rate was defined as the percentage of participants with CR or PR based on mSWAT skin score. mSWAT score represents the product of the %TBSA involvement of each lesion type (patch, plaque, and tumor or ulceration), multiplied by a weighting factor: mSWAT score = (patch %TBSA x 1) + (plaque %TBSA x 2) + (tumor or ulcer %TBSA x 4). The sum of these 3 numbers gave the modified SWAT score, on a 0 (no lesions) to 400 (lesions covering all areas) scale. CR based on mSWAT score was defined as the absence of skin disease. PR was defined as ≥ 50% decrease of the modified SWAT score compared to the Baseline score. |
| Responses in Index Lesions in Participants With Refractory CTCL by Lesion Measurements With Photographic Supporting Documentation | From first dose of study drug up to disease progression or death (up to approximately 2 years) | Index lesions in each participant were selected as four to six of the prominent lesions amenable to bi-dimensional measurements. The longest diameter and its perpendicular measurement were used to determine the surface area and a weighted sum was determined as: Lesion 1 + lesion 2 + … + lesions 6 = Total sum of weighted score where Lesion 1: cm\^2 x \[1 (for patch); 2 (for plaque); 4 (for tumor or ulcer)\]; Lesion 2: cm\^2 x \[1 (for patch); 2 (for plaque); 4 (for tumor or ulcer)\]; Lesion 6: cm\^2 x \[1 (for patch); 2 (for plaque); 4 (for tumor or ulcer)\]. These lesions were photographed at Baseline and at the time of response determined by either mSWAT or PGA |
| ORR of Participants With Resistant CTCL Treated With Oral Panobinostat by Using the Modified PGA to Assess Skin Disease and the Evaluation of Disease in the Viscera, Lymph Nodes and Blood (Circulating Sézary Syndrome Cells) | From first dose of study drug up to disease progression or death, (up to approximately 2 years) | ORR was defined as the percentage of participants with best OR of CR or PR based on PGA scale (OR = CR + PR). The PGA is a 7-point grading scale for the investigator's assessment of the overall extent of improvement or worsening of the participant's disease as compared to Baseline. CR corresponds to Grade 0 (completely clear) of PGA scale and was defined as no evidence of disease; 100% improvement. PR corresponds to Grade 2 (marked improvement) of PGA scale and was defined as significant improvement (≥75%-\<90%); some evidence of disease remains. |
| Response Rate of Participants With Refractory CTCL Using the Physician's Global Assessment of Clinical Condition (PGA) | From first dose of study drug up to disease progression or death, (up to approximately 2 years) | Response rate was defined as the percentage of participants with CR or PR based on PGA scale. PGA is a 7-point grading scale for the investigator's assessment of the overall extent of improvement or worsening of the participant's disease as compared to Baseline. CR corresponds to Grade 0 (Completely clear) on PGA scale and was defined as no evidence of disease; 100% improvement. PR corresponds to Grade 2 (marked improvement) on PGA scale and was defined as significant improvement (≥75% - \<90%); some evidence of disease remains. |
| Time to Response (TTR) | From first dose of study drug up to study completion (approximately 2 years) | TTR was defined as the time from the start of treatment until the first documented evidence of CR or PR among participants who achieved a confirmed CR or PR. |
| Progression-Free Survival (PFS) | From first dose of study drug up to disease progression or death, (up to approximately 2 years) | PFS was defined as the time from the start of treatment until the earliest date of disease progression or death due to any cause, if sooner. |
| Duration of Response (DOR) | From first dose of study drug up to disease progression or death, (up to approximately 2 years) | DOR was defined as the time from first documented evidence of CR or PR until the earliest date of documented progression or death due to any cause among participants who achieved a confirmed CR or PR. The DOR was calculated in two ways. The DOR among responders only included participants who responded to the drug. The overall DOR included non-responders as having a DOR of zero days. |
Countries
United States
Participant flow
Recruitment details
A total of 9 participants were enrolled in the study at 8 investigative sites in the USA from 5 July 2007 to 15 June 2009. Recruitment was stopped on 15 June 2009 (early termination date) due to low prevalence of study population and slow accrual.
Participants by arm
| Arm | Count |
|---|---|
| Panobinostat 20 mg Participants received panobinostat, 20 mg, capsules, orally, thrice weekly on alternate Days 1, 3 and 5 per week of a 28-day treatment cycle until unacceptable toxicity, disease progression and/or physician's discretion to discontinue the treatment. | 9 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Administrative Problems | 1 |
| Overall Study | Death | 1 |
| Overall Study | Disease Progression | 5 |
| Overall Study | New Cancer Therapy | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Panobinostat 20 mg |
|---|---|
| Age, Continuous | 54.8 years STANDARD_DEVIATION 13.29 |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 9 |
| other Total, other adverse events | 9 / 9 |
| serious Total, serious adverse events | 4 / 9 |
Outcome results
Primary
Overall Response Rate (ORR) in Participants With Resistant Cutaneous T-Cell Lymphoma (CTCL) Treated With Oral Panobinostat by Using the Modified Severity-Weighted Assessment Tool (mSWAT)
ORR was defined as the percentage of participants with best overall response (OR) of complete response (CR) or partial response (PR) based on mSWAT score, (OR = CR + PR). mSWAT score represents the product of the percentage total body surface area (%TBSA) involvement of each lesion type (patch, plaque, and tumor or ulceration), multiplied by a weighting factor: modified SWAT score = (patch %TBSA x 1) + (plaque %TBSA x 2) + (tumor or ulcer %TBSA x 4). The sum of these 3 numbers gave the modified SWAT score, on a 0 (no lesions) to 400 (lesions covering all areas) scale. CR based on mSWAT score was defined as the absence of skin disease. PR was defined as ≥ 50% decrease of the modified SWAT score compared to the Baseline score.
Time frame: From first dose of study drug up to disease progression or death, (up to approximately 2 years)
Population: Since the study was terminated early due to low prevalence of study population and slow accrual Since the study was terminated early due to low accrual, no analyses were conducted for this study.
Secondary
Duration of Response (DOR)
DOR was defined as the time from first documented evidence of CR or PR until the earliest date of documented progression or death due to any cause among participants who achieved a confirmed CR or PR. The DOR was calculated in two ways. The DOR among responders only included participants who responded to the drug. The overall DOR included non-responders as having a DOR of zero days.
Time frame: From first dose of study drug up to disease progression or death, (up to approximately 2 years)
Population: Since the study was terminated early due to low prevalence of study population and slow accrual Since the study was terminated early due to low accrual, no analyses were conducted for this study.
Secondary
ORR of Participants With Resistant CTCL Treated With Oral Panobinostat by Using the Modified PGA to Assess Skin Disease and the Evaluation of Disease in the Viscera, Lymph Nodes and Blood (Circulating Sézary Syndrome Cells)
ORR was defined as the percentage of participants with best OR of CR or PR based on PGA scale (OR = CR + PR). The PGA is a 7-point grading scale for the investigator's assessment of the overall extent of improvement or worsening of the participant's disease as compared to Baseline. CR corresponds to Grade 0 (completely clear) of PGA scale and was defined as no evidence of disease; 100% improvement. PR corresponds to Grade 2 (marked improvement) of PGA scale and was defined as significant improvement (≥75%-\<90%); some evidence of disease remains.
Time frame: From first dose of study drug up to disease progression or death, (up to approximately 2 years)
Population: Since the study was terminated early due to low prevalence of study population and slow accrual Since the study was terminated early due to low accrual, no analyses were conducted for this study.
Secondary
Progression-Free Survival (PFS)
PFS was defined as the time from the start of treatment until the earliest date of disease progression or death due to any cause, if sooner.
Time frame: From first dose of study drug up to disease progression or death, (up to approximately 2 years)
Population: Since the study was terminated early due to low prevalence of study population and slow accrual Since the study was terminated early due to low accrual, no analyses were conducted for this study.
Secondary
Response Rate in Participants With Refractory CTCL Using Modified Skin Score
Response rate was defined as the percentage of participants with CR or PR based on mSWAT skin score. mSWAT score represents the product of the %TBSA involvement of each lesion type (patch, plaque, and tumor or ulceration), multiplied by a weighting factor: mSWAT score = (patch %TBSA x 1) + (plaque %TBSA x 2) + (tumor or ulcer %TBSA x 4). The sum of these 3 numbers gave the modified SWAT score, on a 0 (no lesions) to 400 (lesions covering all areas) scale. CR based on mSWAT score was defined as the absence of skin disease. PR was defined as ≥ 50% decrease of the modified SWAT score compared to the Baseline score.
Time frame: From first dose of study drug up to disease progression or death, (up to approximately 2 years)
Population: Since the study was terminated early due to low prevalence of study population and slow accrual Since the study was terminated early due to low accrual, no analyses were conducted for this study.
Secondary
Response Rate of Participants With Refractory CTCL Using the Physician's Global Assessment of Clinical Condition (PGA)
Response rate was defined as the percentage of participants with CR or PR based on PGA scale. PGA is a 7-point grading scale for the investigator's assessment of the overall extent of improvement or worsening of the participant's disease as compared to Baseline. CR corresponds to Grade 0 (Completely clear) on PGA scale and was defined as no evidence of disease; 100% improvement. PR corresponds to Grade 2 (marked improvement) on PGA scale and was defined as significant improvement (≥75% - \<90%); some evidence of disease remains.
Time frame: From first dose of study drug up to disease progression or death, (up to approximately 2 years)
Population: Since the study was terminated early due to low prevalence of study population and slow accrual Since the study was terminated early due to low accrual, no analyses were conducted for this study.
Secondary
Responses in Index Lesions in Participants With Refractory CTCL by Lesion Measurements With Photographic Supporting Documentation
Index lesions in each participant were selected as four to six of the prominent lesions amenable to bi-dimensional measurements. The longest diameter and its perpendicular measurement were used to determine the surface area and a weighted sum was determined as: Lesion 1 + lesion 2 + … + lesions 6 = Total sum of weighted score where Lesion 1: cm\^2 x \[1 (for patch); 2 (for plaque); 4 (for tumor or ulcer)\]; Lesion 2: cm\^2 x \[1 (for patch); 2 (for plaque); 4 (for tumor or ulcer)\]; Lesion 6: cm\^2 x \[1 (for patch); 2 (for plaque); 4 (for tumor or ulcer)\]. These lesions were photographed at Baseline and at the time of response determined by either mSWAT or PGA
Time frame: From first dose of study drug up to disease progression or death (up to approximately 2 years)
Population: Since the study was terminated early due to low prevalence of study population and slow accrual Since the study was terminated early due to low accrual, no analyses were conducted for this study.
Secondary
Time to Response (TTR)
TTR was defined as the time from the start of treatment until the first documented evidence of CR or PR among participants who achieved a confirmed CR or PR.
Time frame: From first dose of study drug up to study completion (approximately 2 years)
Population: Since the study was terminated early due to low prevalence of study population and slow accrual Since the study was terminated early due to low accrual, no analyses were conducted for this study.