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. |
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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 |
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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 the modified Severity-Weighted Assessment Tool (mSWAT) to assess skin disease and the evaluation of disease in the viscera, lymph nodes and blood (circulating SS cells) |
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E.2.2 | Secondary objectives of the trial |
To determine in patients with refractory CTCL, the: • Response rate using the modified Severity-Weighted Assessment Tool (mSWAT) • Response rate using a composite of mSWAT to assess skin disease and the combined evaluation of disease in the viscera, lymph nodes and blood (circulating SS cells) • Response rate using the Physician’s Global Assessment of Clinical Condition (PGA) • Responses in index lesions by lesion measurements and with photographic supporting documentation • To determine the overall response rate of patients with resistant CTCL treated with oral LBH589 by using the Physician’s Global Assessment (PGA) to assess skin disease and the evaluation of disease in the viscera, lymph nodes and blood (circulating SS cells) • Improvement in CTCL-related symptoms and patient-reported outcomes • Duration of response • Time to response • Progression-free survival • Safety and tolerability • Pharmacokinetic (PK) profile
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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. Patients with transformed CTCL are eligible. Disease stage for eligibility is based on the stage at time of study enrollment. NOTE: patients with any history of visceral involvement due to CTCL (i.e. stage IVB disease) are not eligible for this study. 4. Patients must have received at least two prior systemic therapy regimens. 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: • Disease progression on following treatment oral bexarotene, OR • An inadequate response to oral bexarotene treatment defined as stable disease as the best response after at least 3 months of treatment, OR • Intolerance of oral bexarotene defined as patients who discontinued oral bexarotene treatment due to adverse events. • Group 2: Patients who have not had prior oral bexarotene treatment
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E.4 | Principal exclusion criteria |
1. Prior treatment with an HDAC inhibitor for CTCL. 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. Patients who have been previously treated with LBH589. 4. Impaired cardiac function 5. Concomitant use of drugs with a risk of causing torsades de pointes 6. Patients who have received chemotherapy or any investigational drug or undergone major surgery ≤ 3 weeks prior to starting study drug or who have not recovered from side effects of such therapy 7. Less than 3 months since prior electron beam therapy 8. Women who are pregnant or breast feeding, or women of childbearing potential (WOCBP) not willing to use a double method of contraception during the study and 3 months after the end of treatment. One of these methods of contraception must be a barrier method. WOCBP are defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months). Women of childbearing potential (WOCBP) must have a negative serum pregnancy test at baseline. 9. Male patients whose sexual partners are WOCBP not using a double method of contraception during the study and 3 months after the end of treatment. One of these methods of contraception must be a condom.
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E.5 End points |
E.5.1 | Primary end point(s) |
- mSWAT to assess skin disease - The evaluation of disease in the viscera or lymph nodes can CT scan - Blood analysis for Sézary cells - Patient reported outcomes
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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 | 26 |
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 |
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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
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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). |
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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 |