Back to resultsStudy of Oral LBH589 in Adult Participants With Refractory/Resistant Cutaneous T-Cell Lymphoma (CTCL)
Primary Purpose
Cutaneous T-Cell Lymphoma
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Panobinostat
Sponsored by
About this trial
This is an interventional treatment trial for Cutaneous T-Cell Lymphoma focused on measuring Cutaneous T-Cell Lymphoma, adults, Mycosis Fungoides, Sézary Syndrome, CTCL
Eligibility Criteria
Inclusion criteria:
- Written informed consent obtained prior to any screening procedures
- Age greater than or equal to 18 years old
- 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
- 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.
- Baseline multiple-gated acquisition scan (MUGA) or echocardiogram must have demonstrated left ventricular ejection fraction (LVEF) ≥ the lower limit of the institutional normal
- ECOG performance status ≤ 2
Exclusion criteria:
- 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
- Impaired cardiac function
- Concomitant use of drugs with a risk of causing torsades de pointes
- 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
- Less than 3 months since prior electron beam therapy
- 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/exclusion criteria may apply.
Sites / Locations
- University of Alabama at Birmingham/ The Kirklin Clinic
- UCLA Medical Center School of Medicine/ Dpt of Hematology-Oncology
- University of Colorado Health Sciences Center/Anschutz Cancer Pavillion
- Florida Academic Dermatology Centers
- Medical College of Georgia
- Rush Presbyterian Hospital/St. Luke's Medical Center
- St. Louis University Cancer Cennter
- Nebraska Medical Center
- Our Lady of Mercy Medical Center/Comprehensive Cancer Center
- Roswell Park Cancer Institute
- NYU Clinical Cancer Center
- Wake University Health Sciences
- University of Oklahoma-Tulsa
- Craig Okada
- University of Pittsburg Medical Center
- The Jones Clinic
- MD Anderson Cancer Center/University of Texas
- Seattle Cancer Care Alliance
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Panobinostat 20 mg
Arm Description
Participants received panobinostat, 20 milligrams (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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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
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.
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 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.
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.
Full Information
NCT ID
NCT00490776
First Posted
June 21, 2007
Last Updated
August 16, 2021
Sponsor
Novartis Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT00490776
Brief Title
Study of Oral LBH589 in Adult Participants With Refractory/Resistant Cutaneous T-Cell Lymphoma (CTCL)
Official Title
A Phase II Study of Oral LBH589 in Adult Patients With Cutaneous T-Cell Lymphoma Who Are Intolerant to or Have Progressed on or After Prior HDAC Inhibitor
Study Type
Interventional
2. Study Status
Record Verification Date
August 2021
Overall Recruitment Status
Terminated
Why Stopped
Recruitment was stopped on 15 June 2009 (early termination date) due to low prevalence of study population and slow accrual.
Study Start Date
July 5, 2007 (Actual)
Primary Completion Date
September 2009 (Actual)
Study Completion Date
September 22, 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cutaneous T-Cell Lymphoma
Keywords
Cutaneous T-Cell Lymphoma, adults, Mycosis Fungoides, Sézary Syndrome, CTCL
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
9 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Panobinostat 20 mg
Arm Type
Experimental
Arm Description
Participants received panobinostat, 20 milligrams (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.
Intervention Type
Drug
Intervention Name(s)
Panobinostat
Other Intervention Name(s)
LBH589
Intervention Description
Panobinostat, 20 mg, hard gelatin capsules, orally, thrice weekly.
Primary Outcome Measure Information:
Title
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)
Description
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)
Secondary Outcome Measure Information:
Title
Response Rate of Participants With Refractory CTCL Using the Physician's Global Assessment of Clinical Condition (PGA)
Description
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)
Title
Response Rate in Participants With Refractory CTCL Using Modified Skin Score
Description
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)
Title
Responses in Index Lesions in Participants With Refractory CTCL by Lesion Measurements With Photographic Supporting Documentation
Description
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)
Title
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)
Description
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)
Title
Duration of Response (DOR)
Description
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)
Title
Time to Response (TTR)
Description
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)
Title
Progression-Free Survival (PFS)
Description
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)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria:
Written informed consent obtained prior to any screening procedures
Age greater than or equal to 18 years old
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
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.
Baseline multiple-gated acquisition scan (MUGA) or echocardiogram must have demonstrated left ventricular ejection fraction (LVEF) ≥ the lower limit of the institutional normal
ECOG performance status ≤ 2
Exclusion criteria:
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
Impaired cardiac function
Concomitant use of drugs with a risk of causing torsades de pointes
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
Less than 3 months since prior electron beam therapy
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/exclusion criteria may apply.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
University of Alabama at Birmingham/ The Kirklin Clinic
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
UCLA Medical Center School of Medicine/ Dpt of Hematology-Oncology
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
University of Colorado Health Sciences Center/Anschutz Cancer Pavillion
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80010
Country
United States
Facility Name
Florida Academic Dermatology Centers
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Medical College of Georgia
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30912
Country
United States
Facility Name
Rush Presbyterian Hospital/St. Luke's Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
St. Louis University Cancer Cennter
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Nebraska Medical Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198
Country
United States
Facility Name
Our Lady of Mercy Medical Center/Comprehensive Cancer Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10466
Country
United States
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States
Facility Name
NYU Clinical Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Wake University Health Sciences
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Facility Name
University of Oklahoma-Tulsa
City
Tulsa
State/Province
Oklahoma
ZIP/Postal Code
74104
Country
United States
Facility Name
Craig Okada
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
University of Pittsburg Medical Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
The Jones Clinic
City
Germantown
State/Province
Tennessee
ZIP/Postal Code
38138
Country
United States
Facility Name
MD Anderson Cancer Center/University of Texas
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Seattle Cancer Care Alliance
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109-102
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Study of Oral LBH589 in Adult Participants With Refractory/Resistant Cutaneous T-Cell Lymphoma (CTCL)
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