Clinical Trials Register

Summary
EudraCT Number:	2011-001076-18
Sponsor's Protocol Code Number:	26481585LYM2001
National Competent Authority:	Portugal - INFARMED
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-07-28
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Portugal - INFARMED

A.2

EudraCT number

2011-001076-18

A.3

Full title of the trial

A Phase 2, Randomized, Open-label, Multicenter Study of the Histone Deacetylase Inhibitor (HDACi) JNJ-26481585 at Two Dose Levels in Subjects With Previously Treated Stage Ib-IVa Cutaneous T-cell Lymphoma

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

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

A.4.1

Sponsor's protocol code number

26481585LYM2001

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Janssen-Cilag International NV
B.1.3.4	Country	Belgium
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Janssen Research & Development
B.4.2	Country	Belgium
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Janssen-Cilag International NV
B.5.2	Functional name of contact point	Clinical Registry Group
B.5.3	Address:
B.5.3.1	Street Address	Janssen Biologics BV- Archimdesweg 29
B.5.3.2	Town/ city	Leiden
B.5.3.3	Post code	2333CM
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	+ 31(0)715242166
B.5.5	Fax number	+ 31(0)715242110
B.5.6	E-mail	ClinicalTrialsEU@its.jnj.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.2	Product code	JNJ-26481585
D.3.4	Pharmaceutical form	Capsule
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.2	Current sponsor code	JNJ-26481585
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.2	Product code	JNJ-26481585
D.3.4	Pharmaceutical form	Capsule
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.2	Current sponsor code	JNJ-26481585
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Stage Ib-IVa Cutaneous T-cell Lymphoma

E.1.1.1

Medical condition in easily understood language

Cutaneous T-cell Lymphoma (CTCL)

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.0
E.1.2	Level	LLT
E.1.2	Classification code	10011677
E.1.2	Term	Cutaneous T-cell lymphoma
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective is to determine the overall cutaneous response rate (RR) based on the modified Severity Weighted Assessment Tool (mSWAT) criteria.

E.2.2

Secondary objectives of the trial

* 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

E.2.3

Trial contains a sub-study

E.3

Principal 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 3 weeks wash-out period.
5. Stable anti-pruritus regimen (topical corticosteroids or antihistamine) in the preceding 4 weeks
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
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 β-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

E.4

Principal 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.

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint is the overall cutaneous RR (as determined by mSWAT criteria), defined as the proportion of evaluable subjects who achieve a CCR (complete disappearance of all cutaneous disease) or PR (≥ 50% reduction in mSWAT score compared to baseline).

E.5.1.1

Timepoint(s) of evaluation of this end point

every 6 weeks

E.5.2

Secondary end point(s)

* Overall global RR, defined as the proportion of subjects who achieve CR or PR based on the consensus global response score for MF/SS [defined as the total score of tumor, lymph nodes, metastasis, blood (TNMB) staging, ie, cutaneous disease, lymph nodes, viscera and
blood]
* PFS, defined as the interval between the date of randomization and the date of disease progression or death from any cause, whichever occurs first
* 1-year overall survival rate, defined as the Kaplan-Meier (KM) estimate of the proportion of subjects surviving at 1 year post-randomization
* DOR for subjects achieving a CR or PR, defined as the date from the first documentation of CR or PR until the date of first documentation of PD, or death from any cause
* The EORTC QLC C30 and the Pruritus Intensity Assessment Questionnaire scale scores
* Pharmacodynamic markers of JNJ-26481585 response in tumor biopsies and surrogate tissues
* Biomarkers predictive of response to JNJ-26481585 through comparison of expression of tumor; specific markers in responders and non-responders
* Population pharmacokinetics of JNJ-26481585

E.5.2.1

Timepoint(s) of evaluation of this end point

every 12 weeks

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Exploratory Biomarkers Evaluations

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

2 dose levels study

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

France

Germany

Italy

Portugal

Spain

United Kingdom

United States

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

The Study is considered completed with the last study assessment for the last subject participating in the study.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.1.1