E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Adult patients with stages IB to IVA mycosis fungoides (MF) or Sézary syndrome (SS). All patients must have received at least two prior treatment regimens for their MF or SS, at least one of which was a systemic regimen. |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10011679 |
E.1.2 | Term | Cutaneous T-cell lymphoma refractory |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine the response rate of patients with refractory CTCL treated with oral LBH589 as determined by using a modified Severity-Weighted Assessment Tool (mSWAT). |
|
E.2.2 | Secondary objectives of the trial |
To determine in patients with refractory CTCL, the: 1. Response rate using the Physicians Global Assessment of Clinical Condition (PGA) 2. Responses in index lesions by lesion measurements with photographic supporting documentation 3. Improvement in CTCL-related symptoms and patient-reported outcomes 4. Duration of response 5. Time to response 6. Progression-free survival 7. Safety and tolerability 8. Pharmacokinetic (PK) profile of LBH589 9. Potential biological factors that might correlate with efficacy and response.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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, 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. Patients are also eligible if they had an inadequate response to their most recent treatment regimen defined as stable disease as the best response after at least 3 months of therapy. 6. Patients will be accrued to one of two groups: • Group 1: Patients previously treated with oral bexarotene. This group includes patients who had: 1. Disease progression on following treatment oral bexarotene, OR 2. An inadequate response to oral bexarotene treatment defined as stable disease as the best response after at least 3 months of treatment, OR 3. Intolerance of oral bexoratene defined as patients who discontinued oral bexoratene treatment due to adverse events. • Group 2: Patients who have not had prior oral bexarotene treatment. 7. Patients must have specific laboratory values (see protocol) 8. Baseline MUGA or ECHO must demonstrate LVEF ≥ the lower limit of the institutional normal 9. ECOG Performance Status ≤ 2 |
|
E.4 | Principal 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 (details see protocol) 4. Concomitant use of drugs with a risk of causing torsades des 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. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days prior to administration of oral LBH589 8. Male patients whose sexual partners are WOCBP not using effective birth control |
|
E.5 End points |
E.5.1 | Primary end point(s) |
- Efficacy - Response rate
|
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
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 | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
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 | 22 |
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 | Information not present in EudraCT |
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 |
|
E.8.7 | Trial has a data monitoring committee | No |
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
|
Patients may continue treatment with oral LBH589 until they experience e.g. unacceptable toxicity that precludes further treatment, disease progression, and/or at the discretion of the investigator (for details see study protocol). |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |