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

Primary Purpose

Cutaneous T-Cell Lymphoma

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Panobinostat

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

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria:

Written informed consent obtained prior to any screening procedures
Age ≥ 18 years old
Patients with biopsy-confirmed stages IB-IVA mycosis fungoides or Sézary syndrome. Patients with SS who have bone marrow involvement are also eligible.
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.
Patients must have had disease progression on or following their most recent treatment regimen or an inadequate response to their most recent treatment regimen.
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:

Prior treatment with an HDAC inhibitor.
Patients with visceral disease including CNS involvement (i.e. stage IVB CTCL). Note; Patients with SS who have bone marrow involvement are eligible.
Impaired cardiac function
Concomitant use of drugs with a risk of causing torsades de pointes
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
Less than 3 months since prior electron beam therapy
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
Uncontrolled hypertension
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
Concomitant use of CYP3A4/5 inhibitors.
Patients with unresolved diarrhea > CTCAE grade 1
Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral LBH589
Other concurrent severe and/or uncontrolled medical conditions
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

Sites / Locations

University of Alabama at Birmingham/ Kirklin Clinic Kirklin Clinic
City of Hope National Medical Center
University of California at Los Angeles Dept. of Hematology-Oncology
Florida Academic Dermatology Center
Emory University School of Medicine/Winship Cancer Institute Dept. of Hematology (2)
Georgia Health Sciences University Dept.ofMedicalCollegeOfGeorgia
NorthwesternUniv.Med.School/Robert H. Lurie Comp.Cancer Ctr Dept. of NorthwesterUMed
Indiana University Dept. of IU Cancer Center
Boston Medical Center StudyCoordinator:CLBH589B2201
Dana Farber Cancer Institute Deptof DanaFarberCancerInst(3)
University of Michigan Health System Michigan HouseClinTrialsOffice
Wake Forest University Baptist Medical Center OutpatientCmprehensivCancerCtr
University Dermatology Consultants
Oregon Health & Science University Dept. of OHSU Cancer Institute
University of Pittsburgh Medical Center Department of Dermatology
MD Anderson Cancer Center/University of Texas StudyCoordinator:CLBH589B2201
Novartis Investigative Site
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Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Previously treated with oral bexarotene

No prior oral bexarotene treatment

Arm Description

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).

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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 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.

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.

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

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.

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.

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.

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 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.

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 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.

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.

Full Information

NCT ID

NCT00425555

First Posted

January 22, 2007

Last Updated

August 19, 2021

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT00425555

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2021

Overall Recruitment Status

Completed

Study Start Date

January 2007 (undefined)

Primary Completion Date

June 2013 (Actual)

Study Completion Date

June 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

5. Study Description

Brief Summary

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

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

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

139 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Previously treated with oral bexarotene

Arm Type

Experimental

Arm Description

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).

Arm Title

No prior oral bexarotene treatment

Arm Type

Experimental

Arm Description

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).

Intervention Type

Drug

Intervention Name(s)

Panobinostat

Other Intervention Name(s)

LBH589

Primary Outcome Measure Information:

Title

Overall Response Rate of Participants Using the Modified Severity-Weighted Assessment Tool (mSWAT)

Description

Time Frame

Baseline up to 6 Months of Follow up

Secondary Outcome Measure Information:

Title

The Overall Response Rate Using mSWAT Skin Score

Description

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