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

Cutaneous T-Cell Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00425555
• Other study ID #: CLBH589B2201
• Secondary ID: 2006-000880-27
• Status: Completed
• Phase: Phase 2
• Start date: January 2007
• Est. completion date: June 2013

Study information

• Verified date: August 2021
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 139
• Est. completion date: June 2013
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cutaneous T-Cell Lymphoma
• Lymphoma
• Lymphoma, T-Cell
• Lymphoma, T-Cell, Cutaneous

Intervention

Drug:
• Panobinostat

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Australia	Novartis Investigative Site	Parkville	Victoria
Australia	Novartis Investigative Site	South Brisbane	Queensland
Belgium	Novartis Investigative Site	Gent
Belgium	Novartis Investigative Site	Leuven
Belgium	Novartis Investigative Site	Yvoir
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Ottawa	Ontario
Finland	Novartis Investigative Site	Helsinki
France	Novartis Investigative Site	Creteil
France	Novartis Investigative Site	Lyon	Cedex 02
France	Novartis Investigative Site	Paris
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Minden
Germany	Novartis Investigative Site	Würzburg
Hungary	Novartis Investigative Site	Budapest
Italy	Novartis Investigative Site	Ancona	AN
Italy	Novartis Investigative Site	Bologna	BO
Italy	Novartis Investigative Site	Firenze	FI
Italy	Novartis Investigative Site	Napoli
Italy	Novartis Investigative Site	Torino	TO
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Switzerland	Novartis Investigative Site	Zürich
United States	University of Michigan Health System Michigan HouseClinTrialsOffice	Ann Arbor	Michigan
United States	Emory University School of Medicine/Winship Cancer Institute Dept. of Hematology (2)	Atlanta	Georgia
United States	Georgia Health Sciences University Dept.ofMedicalCollegeOfGeorgia	Augusta	Georgia
United States	University of Alabama at Birmingham/ Kirklin Clinic Kirklin Clinic	Birmingham	Alabama
United States	Boston Medical Center StudyCoordinator:CLBH589B2201	Boston	Massachusetts
United States	Dana Farber Cancer Institute Deptof DanaFarberCancerInst(3)	Boston	Massachusetts
United States	NorthwesternUniv.Med.School/Robert H. Lurie Comp.Cancer Ctr Dept. of NorthwesterUMed	Chicago	Illinois
United States	University Dermatology Consultants	Cincinnati	Ohio
United States	City of Hope National Medical Center	Duarte	California
United States	MD Anderson Cancer Center/University of Texas StudyCoordinator:CLBH589B2201	Houston	Texas
United States	Indiana University Dept. of IU Cancer Center	Indianapolis	Indiana
United States	University of California at Los Angeles Dept. of Hematology-Oncology	Los Angeles	California
United States	Florida Academic Dermatology Center	Miami	Florida
United States	University of Pittsburgh Medical Center Department of Dermatology	Pittsburgh	Pennsylvania
United States	Oregon Health & Science University Dept. of OHSU Cancer Institute	Portland	Oregon
United States	Wake Forest University Baptist Medical Center OutpatientCmprehensivCancerCtr	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Canada,  Finland,  France,  Germany,  Hungary,  Italy,  Spain,  Switzerland, 

References & Publications (1)

Duvic M, Dummer R, Becker JC, Poulalhon N, Ortiz Romero P, Grazia Bernengo M, Lebbé C, Assaf C, Squier M, Williams D, Marshood M, Tai F, Prince HM. Panobinostat activity in both bexarotene-exposed and -naïve patients with refractory cutaneous T-cell lymph — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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