Clinical trial NCT00425555: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cutaneous T-Cell Lymphoma
Keywords: Cutaneous T-Cell Lymphoma, adults
Mycosis Fungoides
Sézary Syndrome
CTCL
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2007-01-23
Enrollment: 139
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Overall Response Rate of Participants Using the Modified Severity-Weighted Assessment Tool (mSWAT)
timeFrame: Baseline up to 6 Months of Follow up
Secondary outcomes:
measure: The Overall Response Rate Using mSWAT Skin Score
timeFrame: Baseline up to Cycle 12, an average of 12 months
measure: Time to Response for Responders
timeFrame: Baseline up to Cycle 12, an average of 12 months
measure: Duration of Response (DOS)
timeFrame: Baseline up to Cycle 12, an average of 12 months
measure: Progression-free Survival (PFS)
timeFrame: Baseline up to Cycle 12, an average of 12 months
measure: Skindex-29 Measurements of Average Sub-scores for Emotions From Baseline up to Cycle 12
timeFrame: Baseline up to Cycle 12, an average of 12 months
measure: Skindex-29 Measurements of Average Sub-scores for Functioning From Baseline up to Cycle 12
timeFrame: Baseline up to Cycle 12, an average of 12 months
measure: Skindex-29 Measurements of Average Sub-scores for Physical Symptoms From Baseline up to Cycle 12
timeFrame: Baseline up to Cycle 12, an average of 12 months
measure: Maximum Plasma Concentration (Cmax) of Panobinostat
timeFrame: Pre-dose, 0.25, 1-2, and 3-4 hours post dose on Day 1 and Day 8
measure: Time to Peak Concentration (Tmax) of Panobinostat
timeFrame: Pre-dose, 0.25, 1-2, and 3-4 hours post dose on Day 1 and Day 8
measure: Area Under the Plasma Concentration AUC0-24, AUC0-48 and AUC 0-infinity of Panobinostat
timeFrame: Pre-dose, 0.25, 1-2, and 3-4 hours post dose on Day 1 and Day 8
measure: Time of Clast (Tlast) of Panobinostat
timeFrame: Pre-dose, 0.25, 1-2, and 3-4 hours post dose on Day 1 and Day 8
measure: Last Observed Plasma Concentration (Clast) of Panobinostat
timeFrame: Pre-dose, 0.25, 1-2, and 3-4 hours post dose on Day 1 and Day 8
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham/ Kirklin Clinic Kirklin Clinic
state: Alabama
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Los Angeles
country: United States
facility: University of California at Los Angeles Dept. of Hematology-Oncology
state: California
city: Miami
country: United States
facility: Florida Academic Dermatology Center
state: Florida
city: Atlanta
country: United States
facility: Emory University School of Medicine/Winship Cancer Institute Dept. of Hematology (2)
state: Georgia
city: Augusta
country: United States
facility: Georgia Health Sciences University Dept.ofMedicalCollegeOfGeorgia
state: Georgia
city: Chicago
country: United States
facility: NorthwesternUniv.Med.School/Robert H. Lurie Comp.Cancer Ctr Dept. of NorthwesterUMed
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Dept. of IU Cancer Center
state: Indiana
city: Boston
country: United States
facility: Boston Medical Center StudyCoordinator:CLBH589B2201
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute Deptof DanaFarberCancerInst(3)
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Health System Michigan HouseClinTrialsOffice
state: Michigan
city: Winston-Salem
country: United States
facility: Wake Forest University Baptist Medical Center OutpatientCmprehensivCancerCtr
state: North Carolina
city: Cincinnati
country: United States
facility: University Dermatology Consultants
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University Dept. of OHSU Cancer Institute
state: Oregon
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center Department of Dermatology
state: Pennsylvania
city: Houston
country: United States
facility: MD Anderson Cancer Center/University of Texas StudyCoordinator:CLBH589B2201
state: Texas
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: South Brisbane
country: Australia
facility: Novartis Investigative Site
state: Queensland
city: Parkville
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Gent
country: Belgium
facility: Novartis Investigative Site
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: Yvoir
country: Belgium
facility: Novartis Investigative Site
city: Ottawa
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Helsinki
country: Finland
facility: Novartis Investigative Site
city: Lyon
country: France
facility: Novartis Investigative Site
state: Cedex 02
city: Creteil
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Minden
country: Germany
facility: Novartis Investigative Site
city: Würzburg
country: Germany
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Ancona
country: Italy
facility: Novartis Investigative Site
state: AN
city: Bologna
country: Italy
facility: Novartis Investigative Site
state: BO
city: Firenze
country: Italy
facility: Novartis Investigative Site
state: FI
city: Torino
country: Italy
facility: Novartis Investigative Site
state: TO
city: Napoli
country: Italy
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Zürich
country: Switzerland
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: 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.