Stage Ib-IVa Cutaneous T-cell Lymphoma MedDRA version: 14.1 Level: LLT Classification code 10011677 Term: Cutaneous T-cell lymphoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Code: JNJ-26481585
Pharmaceutical Form: Capsule
Current Sponsor code: JNJ-26481585
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1 -
Product Code: JNJ-26
Sponsors
Janssen-Cilag International NV
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. At least 18 years of age, or the legal age of consent in the jurisdiction in which the study is taking place 2. Eastern Cooperative Oncology Group (ECOG) performance status score 0 to 2 3. Histopathologically confirmed CTCL, either mycosis fungoides or Sézary syndrome Stage Ib-IVa 4. Relapsed or refractory disease following at least 1 prior systemic therapy for CTCL. PUVA is considered skin-directed therapy and not systemic therapy. Subjects must have recovered from toxicity related to prior systemic therapy after at least a 2 week wash-out period. 5. Stable anti-pruritus regimen (topical corticosteroids or antihistamine) in the preceding 28 days. 6. Measurable disease with at least 1 skin lesion (patch, plaque, or tumor) = 1 cm in the longest diameter 7. Adequate liver function as determined by serum total bilirubin levels =1.5 x upper limit of normal (ULN), and serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels =2.5 x ULN 8. Adequate bone marrow function, as determined by an absolute neutrophil count (ANC)=1200/mm3 (or =1.2x10 to the 9th/L); a platelet count =100,000/mm3 (or =100x10 to the 9th/L) and a hemoglobin level greater than 9 g/dL (or=90 g/L), in the absence of transfusion requirements or cytokine support for 7 days prior to enrolling on the study 9. Serum potassium, calcium (corrected for albumin level), magnesium must be within institutional normal limits.Electrolyte supplementation is recommended to maintain electrolyte levels toward the high end of the normal limits (see Section 8.2). 10. LVEF within institutional normal limits, as determined by MUGA or echocardiography 11. Adequate renal function as determined by serum creatinine levels =1.5xULN 12. If a woman, before study entry she must be * postmenopausal (> 45 years of age with amenorrhea for at least 18 months) * surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy) * if heterosexually active, practicing an effective method of birth control (eg, prescription oral contraceptives, contraceptive injections, contraceptive patch, intrauterine device, double-barrier method, male partner sterilization) before enrollment, throughout the study, and up to 6 months after stopping study drug 13. Negative pregnancy test (urine or serum ß-hCG) at Screening (applicable to women of child bearing potential who are sexually active) at most 7 days prior to starting treatment 14. Men must agree to use a double barrier method of birth control and to not donate sperm during the study and for 6 months after receiving the last dose of study drug 15. Subjects must have signed an informed consent document indicating that they understand the purpose and procedures required, and are willing to participate in the study 16. To participate in the optional pharmacogenomic component of this study, subjects must have signed the informed consent form for pharmacogenomic research indicating willingness to participate in the pharmacogenomic component of the study (where local regulations permit). Refusal to give consent for this component does not exclude a subject from participation in the clinical study Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 13 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: 1. Prior histone-deacetylase inhibitor therapy for CTCL 2. Concurrent systemic corticosteroid dose > 10 mg/day of prednisone or equivalent (stable use of =10 mg/day of prednisone for =1 month before study entry is allowed) 3. Major surgery or radiotherapy within 3 weeks before study drug administration. Focal radiotherapy for local disease control is allowed. Subjects must have recovered from prior radiotherapy or surgery related toxicity 4. Other malignancy within past 5 years. Exceptions include: basal or non-metastatic squamous cell carcinoma of the skin, cervical carcinoma in situ, or Fédération Internationale de Gynécologie et d’Obstétrique Stage 1 carcinoma of the cervix, prostate intraepithelial neoplasia and biochemical relapse free = 3 years 5. Unstable angina or myocardial infarction within the preceding 12 months; congestive heart failure New York Heart Association Class II-IV; known presence of dilated, hypertrophic, or restrictive cardiomyopathy; or any other cardiac abnormality that, in the opinion of the investigator, medical monitor, or consultant cardiologist, may place the subject at an unacceptably increased risk with study drug 6. History of any of the following: sustained ventricular tachycardia, ventricular fibrillation, Torsades de Pointes, atrial fibrillation, cardiac arrest, Mobitz II second degree heart block, or third degree heart block; QTc at Screening > 450 ms in males / > 470 ms in females; family history of short QT syndrome, long QT syndrome; obligate use of a cardiac pacemaker. Use of medications that may cause Torsades de Pointes; any of these medications must be discontinued for at least 5 half-lives prior to the first dose of JNJ-26481585. 7. Use of potent inhibitors of CYP3A4/A5 8. Known HIV/AIDS 9. Uncontrolled concurrent illness including, but not limited to, poorly controlled hypertension or diabetes, ongoing clinically significant active infection requiring systemic antibiotics, or psychiatric illness/social situation that may potentially impair subject’s compliance with study procedures 10. Planned major surgery during study period 11. Inadequate gastrointestinal absorption status (status post-gastrectomy, upper gastrointestinal tract obstruction, inability to swallow) 12. Requires hematopoietic growth factors or transfusion of blood products to meet eligibility criteria 13. Any condition that, in the opinion of the investigator, would compromise the well-being of the subject or the study, or prevent the subject from meeting or performing study requirements 14. Pregnant or breast-feeding NOTE: Investigators should ensure that all study enrollment criteria have been met at Screening. If a subject's status changes (including laboratory results) after Screening but before first dose of study drug is given such that they now meet an exclusion criterion, they should be excluded from participation in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to determine the overall cutaneous response rate (RR) based on the modified Severity Weighted Assessment Tool (mSWAT) criteria.;Secondary Objective: * To determine the overall global RR based on consensus global response score for mycosis fungoides (MF) / Sézary Syndrome (SS) (mSWAT + nodes/viscera + blood) * To evaluate the safety profile of JNJ-26481585 * To determine the duration of response (DOR) * To estimate progression free survival (PFS) * To estimate 1-year overall survival rate * To explore the effect of JNJ-26481585 on symptoms and capacity to function [patient reported outcomes (PROs)] * To assess pharmacodynamic markers of JNJ-26481585 activity in tumor biopsies and surrogate tissues * To explore biomarkers predictive of response to JNJ-26481585 * To explore the population pharmacokinetics of JNJ-26481585;Primary end point(s): To determine overall cutaneous response (RR) rate, based on modified Severity Weighted Assessment Tool (mSWAT) criteria;Timepoint(s) of evaluation of this end point: Up to two years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. To determine overall global RR based on consensus global response score for mycosis fungoides (MF) / Sézary Syndrome (SS) (mSWAT + nodes/viscera + blood) 2. To evaluate adverse events 3. To determine the duration ofresponse (DOR) 4. To estimate progression-free survival (PFS) 5. To estimate 1-year overall survival (OS) rate 6.To assess pharmacodynamic markers of JNJ-26481585 activity in tumor biopsies and surrogate tissues 7. To explore biomarkers predictive of response to JNJ-26481585 8. To explore the population pharmacokinetics (PK) of JNJ-26481585 9. The European Organization for Research and Treatment (EORTC QLQC30) and the Pruritus Intensity Assessment Questionnaire scale scores;Timepoint(s) of evaluation of this end point: 1. Up to two years 2. Up to two years 3.First documentation of CR or PR until the date of first documentation of progressive disease (PD), or death 4.First dose of study drug and the date of disease progression or death 5.First dose of study drug until death (up to 2 years) 6. No timepoint of evaluation 7. No timpoint of evaluation 8. No timepoint of evauation 9. No timepoint of evaluation | — |
Countries
France, Germany, Italy, Portugal, Spain, United Kingdom, United States
Contacts
Public ContactClinical Registry Group
Janssen-Cilag International NV
Outcome results
None listed