Study of Oral LBH589 in Adult Participants With Refractory/Resistant Cutaneous T-Cell Lymphoma (CTCL)

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

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.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham/ The Kirklin Clinic
  • California
    • Los Angeles, California, United States, 90095
      • UCLA Medical Center School of Medicine/ Dpt of Hematology-Oncology
  • Colorado
    • Aurora, Colorado, United States, 80010
      • University of Colorado Health Sciences Center/Anschutz Cancer Pavillion
  • Florida
    • Miami, Florida, United States, 33136
      • Florida Academic Dermatology Centers
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Medical College of Georgia
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush Presbyterian Hospital/St. Luke's Medical Center
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • St. Louis University Cancer Cennter
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • Nebraska Medical Center
  • New York
    • Bronx, New York, United States, 10466
      • Our Lady of Mercy Medical Center/Comprehensive Cancer Center
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • New York, New York, United States, 10016
      • Nyu Clinical Cancer Center
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake University Health Sciences
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74104
      • University of Oklahoma-Tulsa
  • Oregon
    • Portland, Oregon, United States, 97239
      • Craig Okada
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburg Medical Center
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • The Jones Clinic
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center/University of Texas
  • Washington
    • Seattle, Washington, United States, 98109-102
      • Seattle Cancer Care Alliance

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 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 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/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Panobinostat 20 mg; 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.	Drug: Panobinostat; Panobinostat, 20 mg, hard gelatin capsules, orally, thrice weekly.; Other Names: LBH589

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From first dose of study drug up to disease progression or death, (up to approximately 2 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From first dose of study drug up to disease progression or death, (up to approximately 2 years)
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.	From first dose of study drug up to disease progression or death, (up to approximately 2 years)
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	From first dose of study drug up to disease progression or death (up to approximately 2 years)
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.	From first dose of study drug up to disease progression or death, (up to approximately 2 years)
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.	From first dose of study drug up to disease progression or death, (up to approximately 2 years)
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.	From first dose of study drug up to study completion (approximately 2 years)
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.	From first dose of study drug up to disease progression or death, (up to approximately 2 years)

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): July 5, 2007
• Primary Completion (Actual): September 1, 2009
• Study Completion (Actual): September 22, 2009

Study Registration Dates

• First Submitted: June 21, 2007
• First Submitted That Met QC Criteria: June 21, 2007
• First Posted (Estimate): June 25, 2007

Study Record Updates

• Last Update Posted (Actual): August 18, 2021
• Last Update Submitted That Met QC Criteria: August 16, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: adults; CTCL; Mycosis Fungoides; Sézary Syndrome; Cutaneous T-Cell Lymphoma
• 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: CLBH589B2212

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No