A Study of the Histone Deacetylase Inhibitor (HDACi) JNJ-26481585 in Patients With Previously Treated Stage Ib-IVa Cutaneous T-cell Lymphoma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01486277
First received: November 29, 2011
Last updated: March 16, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Lymphoma, T-Cell, Cutaneous
Drug: JNJ 26481585, 12 mg
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Janssen Research & Development, LLC:

Primary Outcome Measures:
  • Number of participants who will achieve overall cutaneous Response Rate (RR) based on modified Severity Weighted Assessment Tool (mSWAT) criteria [ Time Frame: 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 ] [ Designated as safety issue: No ]
    The RR is defined as the number of participants who will achieve a complete response (CR) or partial response (PR). mSWAT criteria is used to evaluate the skin tumor burden. The investigator will determine the percentage of total body surface area (TBSA) affected by patches, plaques or tumors in 12 body regions, using the participant's palm and fingers representing 1% of TBSA. CR is defined as 100% clearance of skin lesions and PR is defined as 50% to 99 % clearance of skin lesions from baseline without occurrence of a new tumor.


Secondary Outcome Measures:
  • Number of participants who will achieve global Response Rate (RR) based on based on consensus global response score [ Time Frame: 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 ] [ Designated as safety issue: No ]
    The RR is defined as the number of participants who will achieve a complete response (CR) or partial response (PR). Global response score provides uniformity in the assessment of response and utilizes all component of the tumor-node-metastasis-blood staging (ie, skin, nodes, viscera and blood). Complete response is defined as complete disappearance of all clinical evidence of disease (all categories have CR/ non-involved [NI]) and PR is defined as regression of measurable disease (all categories do not have a CR/NI and no category has a PD and if any other category involved at baseline, at least one has a CR or PR).

  • Progression-Free Survival (PFS) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    PFS is defined as the interval between the date of administration of the first dose of study medication and the date of disease progression or death from any cause, whichever occurs first.

  • Kaplan-MeierEstimates of 1-year overall survival (OS) rate [ Time Frame: 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 ] [ Designated as safety issue: No ]
    1-year OS rate is defined as the number of participants surviving at 1 year after the date of administration of the first dose of study medication.

  • Duration of response (DOR) for participants achieving Complete Response (CR) or Partial Response (PR) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    DOR for participants achieving a CR or PR is defined as the date from the first documentation of CR or PR until the date of first documentation of progressive disease, or death from any cause.

  • The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    EORTC QLQ-C30 is a questionnaire to assess quality of life of cancer patients. It is composed of 30 items, multi-item measure (28 items) and 2 single-item measures. For the multiple item measure, 4-point scale is used and the score for each item range from "1 = not at all" to "4 = very much". Higher scores indicate worsening. The 2 single-item measure involves question about the overall health and overall quality of life which will be rated on a 7-point scale ranging from "1 = very poor" to "7 = excellent". Lower scores indicate worsening.

  • Pruritus Intensity Assessment Questionnaire scale scores [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Pruritus Intensity Assessment Questionnaire is an 11-point scale that requires the participant to rate the intensity of their pruritus. The scores range from '0= no pruritus; 10 = worst imaginable'. Pruritus relief will be defined as a 3 or more point decrease in participant who have a baseline pruritus score of 3 or more points or complete resolution of pruritus for 3 or more continuous weeks without an increase in the use of antipruritic medications. Higher score indicates worsening.

  • Number of participants with adverse events [ Time Frame: Up to 2 years after 6 months enrollment of the last participant ] [ Designated as safety issue: Yes ]

Enrollment: 26
Study Start Date: November 2011
Estimated Study Completion Date: November 2014
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: JNJ-26481585 Drug: JNJ 26481585, 12 mg
Participants will receive JNJ 26481585 12 mg capsule orally (by mouth) on Days 1, 3, and 5 of each week in a 21-day treatment cycle, 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).

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 JNJ-26481585) 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01486277

Locations
United States, Pennsylvania
Pittsburgh, Pennsylvania, United States
France
Nantes Cedex 1, France
Paris, France
Pessac, France
Germany
Kiel, Germany
Minden, Germany
Portugal
Lisboa, Portugal
Porto, Portugal
Spain
Madrid N/A, Spain
Málaga, Spain
Valencia, Spain
United Kingdom
London, United Kingdom
Manchester, United Kingdom
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
  More Information

No publications provided

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT01486277     History of Changes
Obsolete Identifiers: NCT01389960
Other Study ID Numbers: CR018640, 2011-001076-18, 26481585LYM2001
Study First Received: November 29, 2011
Last Updated: March 16, 2014
Health Authority: United States: Food and Drug Administration
Germany: Ethics Commission

Keywords provided by Janssen Research & Development, LLC:
Lymphoma, T-Cell, Cutaneous
T-cell lymphoma
Lymphoma
Histone Deacetylase Inhibitor
JNJ-26481585

Additional relevant MeSH terms:
Lymphoma
Lymphoma, T-Cell
Lymphoma, T-Cell, Cutaneous
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 16, 2014