Study of Oral LBH589 in Adult Patients With Refractory Cutaneous T-Cell Lymphoma

A Phase II Study of Oral LBH589 in Adult Patients With Refractory Cutaneous T-Cell Lymphoma

This study will evaluate the safety and efficacy of LBH489B in adult patients with refractory Cutaneous T-Cell Lymphoma.

Study Overview

• Status: Completed
• Conditions: Cutaneous T-Cell Lymphoma
• Intervention / Treatment: Drug: Panobinostat

• Study Type: Interventional
• Enrollment (Actual): 139
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1425AUM
    • Novartis Investigative Site
  • Buenos Aires
    • Caba, Buenos Aires, Argentina, C1221ADC
      • Novartis Investigative Site
• Australia
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Novartis Investigative Site
  • Victoria
    • Parkville, Victoria, Australia, 3050
      • Novartis Investigative Site
• Belgium
  • Gent, Belgium, 9000
    • Novartis Investigative Site
  • Leuven, Belgium, 3000
    • Novartis Investigative Site
  • Yvoir, Belgium, 5530
    • Novartis Investigative Site
• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • Novartis Investigative Site
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Novartis Investigative Site
• Finland
  • Helsinki, Finland, 00250 HUS
    • Novartis Investigative Site
• France
  • Creteil, France, 94010
    • Novartis Investigative Site
  • Paris, France, 75010
    • Novartis Investigative Site
  • Cedex 02
    • Lyon, Cedex 02, France, 69288
      • Novartis Investigative Site
• Germany
  • Berlin, Germany, 13353
    • Novartis Investigative Site
  • Minden, Germany, 32423
    • Novartis Investigative Site
  • Würzburg, Germany, 97080
    • Novartis Investigative Site
• Hungary
  • Budapest, Hungary, H-1085
    • Novartis Investigative Site
• Italy
  • Napoli, Italy, 80131
    • Novartis Investigative Site
  • AN
    • Ancona, AN, Italy, 60126
      • Novartis Investigative Site
  • BO
    • Bologna, BO, Italy, 40138
      • Novartis Investigative Site
  • FI
    • Firenze, FI, Italy, 50129
      • Novartis Investigative Site
  • TO
    • Torino, TO, Italy, 10126
      • Novartis Investigative Site
• Spain
  • Madrid, Spain, 28041
    • Novartis Investigative Site
  • Madrid, Spain, 28006
    • Novartis Investigative Site
  • Catalunya
    • Barcelona, Catalunya, Spain, 08036
      • Novartis Investigative Site
• Switzerland
  • Zürich, Switzerland, 8091
    • Novartis Investigative Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-0006
      • University of Alabama at Birmingham/ Kirklin Clinic Kirklin Clinic
  • California
    • Duarte, California, United States, 91010-3000
      • City of Hope National Medical Center
    • Los Angeles, California, United States, 90095
      • University of California at Los Angeles Dept. of Hematology-Oncology
  • Florida
    • Miami, Florida, United States, 33136
      • Florida Academic Dermatology Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University School of Medicine/Winship Cancer Institute Dept. of Hematology (2)
    • Augusta, Georgia, United States, 30912
      • Georgia Health Sciences University Dept.ofMedicalCollegeOfGeorgia
  • Illinois
    • Chicago, Illinois, United States, 60611
      • NorthwesternUniv.Med.School/Robert H. Lurie Comp.Cancer Ctr Dept. of NorthwesterUMed
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Dept. of IU Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center StudyCoordinator:CLBH589B2201
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute Deptof DanaFarberCancerInst(3)
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Health System Michigan HouseClinTrialsOffice
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Baptist Medical Center OutpatientCmprehensivCancerCtr
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University Dermatology Consultants
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University Dept. of OHSU Cancer Institute
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center Department of Dermatology
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center/University of Texas StudyCoordinator:CLBH589B2201

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Previously treated with oral bexarotene; Participants received Panobinostat 20 milligrams per day (mg/day) capsule orally, once a day (OD) on 3 days per week. (Monday, Wednesday and Friday or alternative Day 1, 3 and 5).	Drug: Panobinostat; Other Names: LBH589
Experimental: No prior oral bexarotene treatment; Participants received Panobinostat 20 milligrams per day (mg/day) capsule orally, once a day (OD) on 3 days per week. (Monday, Wednesday and Friday or alternative Day 1, 3 and 5).	Drug: Panobinostat; Other Names: LBH589

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline up to 6 Months of Follow up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline up to Cycle 12, an average of 12 months
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.	Baseline up to Cycle 12, an average of 12 months
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.	Baseline up to Cycle 12, an average of 12 months
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	Baseline up to Cycle 12, an average of 12 months
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.	Baseline up to Cycle 12, an average of 12 months
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.	Baseline up to Cycle 12, an average of 12 months
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.	Baseline up to Cycle 12, an average of 12 months
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.	Pre-dose, 0.25, 1-2, and 3-4 hours post dose on Day 1 and Day 8
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.	Pre-dose, 0.25, 1-2, and 3-4 hours post dose on Day 1 and Day 8
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.	Pre-dose, 0.25, 1-2, and 3-4 hours post dose on Day 1 and Day 8
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.	Pre-dose, 0.25, 1-2, and 3-4 hours post dose on Day 1 and Day 8
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.	Pre-dose, 0.25, 1-2, and 3-4 hours post dose on Day 1 and Day 8

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Duvic M, Dummer R, Becker JC, Poulalhon N, Ortiz Romero P, Grazia Bernengo M, Lebbe C, Assaf C, Squier M, Williams D, Marshood M, Tai F, Prince HM. Panobinostat activity in both bexarotene-exposed and -naive patients with refractory cutaneous T-cell lymphoma: results of a phase II trial. Eur J Cancer. 2013 Jan;49(2):386-94. doi: 10.1016/j.ejca.2012.08.017. Epub 2012 Sep 13.

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Actual): June 1, 2013
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: January 22, 2007
• First Submitted That Met QC Criteria: January 22, 2007
• First Posted (Estimate): January 23, 2007

Study Record Updates

• Last Update Posted (Actual): August 20, 2021
• Last Update Submitted That Met QC Criteria: August 19, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: CTCL; Mycosis Fungoides; Sézary Syndrome; Cutaneous T-Cell Lymphoma, adults
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Lymphoma, T-Cell, Cutaneous; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Histone Deacetylase Inhibitors; Panobinostat
• Other Study ID Numbers: CLBH589B2201; 2006-000880-27 (EudraCT Number)