Clinical trial NCT01486277: A Study of the Histone Deacetylase Inhibitor (HDACi) Quisinostat (JNJ-26481585) in Patients With Previously Treated Stage Ib-IVa Cutaneous T-cell Lymphoma
Official title: A Phase 2, Single-arm, Open-label, Multicenter Study of the Histone Deacetylase Inhibitor (HDACi) JNJ-26481585 in Subjects With Previously Treated Stage Ib-IVa Cutaneous T-cell Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lymphoma, T-Cell, Cutaneous
Keywords: Lymphoma, T-Cell, Cutaneous
T-cell lymphoma
Lymphoma
Histone Deacetylase Inhibitor
JNJ-26481585
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2011-12-06
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the overall cutaneous response rate (participants who achieve a complete response or partial response) based on the modified severity weighted assessment tool criteria.

Detailed description: This is a single-arm (group), open-label (all people know the identity of the intervention), and multicenter study. The study consists of 3 phases including, the screening phase (within 28 days prior to the start of study medication), treatment phase (participants will receive quisinostat) and follow-up phase (30 days after the last dose of study medication until death or clinical cutoff). Clinical cut-off is defined as when the last participant will be assessed with progressive disease or died, or 6 months after the last participant enrolled, whichever occurs first. However, if any participants are still receiving study treatment at the time of clinical cut-off, these participants will enter a long-term extension phase and will continue to receive study medication until a reason for discontinuation is met (ie, disease progression, toxicity, availability of other effective medications that the participant may receive, or treating physician advice). The long-term extension phase will continue for a maximum of 2 years beyond the clinical cut-off for primary analysis. Safety will be evaluated by the assessment of adverse events, vital signs, physical examination, 12-lead electrocardiogram, and clinical laboratory tests which will be monitored in this study. Any participants responding to treatment at the end of the 2-year long-term extension phase will be able to continue to receive quisinostat as long as they are assessed by the investigator as not meeting treatment discontinuation criteria; during this time, only information related to serious adverse events will be collected.

Eligibility criteria: Inclusion Criteria:

* Histopathologically confirmed cutaneous T-cell lymphoma (CTCL), either mycosis fungoides or sezary syndrome Stage Ib-IVa
* Relapsed or refractory (unresponsive) disease following at least 1 prior systemic therapy for CTCL, except psoralen and long-wave ultraviolet radiation (it is considered skin-directed therapy and not systemic therapy)
* Stable anti-pruritus regimen (topical corticosteroids or antihistamine) in the preceding 28 days
* Measurable disease with at least 1 skin lesion (patch, plaque, or tumor) 1 cm or greater than 1 cm in the longest diameter laboratory function tests and bone marrow test
* Agrees to protocol defined use of effective contraception
* Adequate laboratory function tests and bone marrow test

Exclusion Criteria:

* Prior histone-deacetylase inhibitor therapy for CTCL
* Concurrent systemic corticosteroid dose greater than 10 mg per day of prednisone or equivalent (stable use of 10 mg or less than 10 mg per day of prednisone for 1 month or more before study entry is allowed)
* Major surgery or radiotherapy within 3 weeks before the start of the study medication
* Unstable angina or heart attack within the preceding 12 months, congestive heart failure New York Heart Association Class II-IV, known presence of dilated, hypertrophic, or restrictive cardiomyopathy
* Inadequate gastrointestinal absorption status
* Use of potent inhibitors of CYP3A4/A5
* Positive human immunodeficiency virus

Primary outcomes:
measure: Number of participants who will achieve overall cutaneous Response Rate (RR) based on modified Severity Weighted Assessment Tool (mSWAT) criteria
timeFrame: From screening until progressive disease or confirmed lost to follow-up or death or start of alternate therapy, or withdrawal from the study; as assessed for approximately 6 months after the enrollment of the last participant
Secondary outcomes:
measure: Number of participants who will achieve global Response Rate (RR) based on based on consensus global response score
timeFrame: From screening until progressive disease or confirmed lost to follow-up or death from any cause or start of alternate therapy, or withdrawal from the study; as assessed for approximately 6 months after the enrollment of the last participant
measure: Progression-Free Survival (PFS)
timeFrame: From the date of administration of the first dose of study medication until progressive disease or death from any cause, whichever occurs first; as assessed for approximately 6 months after the enrollment of the last participant
measure: Kaplan-Meier Estimates of 1-year overall survival (OS) rate
timeFrame: From the date of administration of the first dose of study medication up to the date of progressive disease or death, whichever occurs first; as assessed up to 1 year
measure: Duration of response (DOR) for participants achieving Complete Response (CR) or Partial Response (PR)
timeFrame: First documentation of CR or PR until the date of first documentation of progressive disease, or death from any cause; as assessed for approximately 6 months after the enrollment of the last participant
measure: The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)
timeFrame: From screening until progressive disease or confirmed lost to follow-up or death from any cause or start of alternate therapy, or withdrawal from the study; as assessed for approximately 6 months after the enrollment of the last participant
measure: Pruritus Intensity Assessment Questionnaire scale scores
timeFrame: From screening until progressive disease or confirmed lost to follow-up or death from any cause or start of alternate therapy, or withdrawal from the study; as assessed for approximately 6 months after the enrollment of the last participant
measure: Number of participants with adverse events
timeFrame: Up to 2 years after 6 months enrollment of the last participant
Other outcomes:
Locations:
city: Pittsburgh
country: United States
state: Pennsylvania
city: Nantes Cedex 1
country: France
city: Paris
country: France
city: Pessac
country: France
city: Kiel
country: Germany
city: Minden
country: Germany
city: Lisboa
country: Portugal
city: Porto
country: Portugal
city: Madrid N/A
country: Spain
city: Málaga
country: Spain
city: Valencia
country: Spain
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: