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 overall response rate of patients with refractory CTCL treated with LBH589 using the modified Severity-Weighted Assessment Tool (mSWAT) to assess skin disease and the evaluation of disease in the viscera, and lymph nodes. |
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E.2.2 | Secondary objectives of the trial |
To determine in patients with refractory CTCL, the: 1. Response rate using modified Severity Weighted Assessment (mSWAT) skin score 2. 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) 3. Response rate using the Physicians Global Assessment of Clinical Condition (PGA) 4. Responses in index lesions by lesion measurements with photographic supporting documentation 5. 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 evaluatin of disease in the viscera, lymph nodes and blood (circulating SS cells) 6. Improvement in CTCL-related symptoms and patient-reported outcomes 7. Duration of response 8. Time to response 9. Progression-free survival 10. Safety and tolerability 11. Pharmacokinetic (PK) profile of LBH589 |
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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. 4. Patients must have received at least two prior systemic therapy regimens. Systemic regimens include oral bexarotene, PUVA, photophoresis, oral corticosteroids, total skin electron bean therapy, immunotherapy, chemotherapy such as methotrexate, and biological response modifiers such as 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 or following treatment with 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 to 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. 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 |
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E.4 | Principal exclusion criteria |
1. Prior treatment with an HDAC inhibitor for CTCL. 2. Patients who have been previously treated with LBH589. 3. Patients with any history of visceral disease including CNS involvement (i.e. history of stage IVB CTCL even if the IVB disease has been down-staged at the time of study enrollment). Note: Patients who have SS with bone marrow involvement are eligible. 4. Impaired cardiac function (details see protocol) 5. Uncontrolled hypertension 6. Concomitant use of any anti-cancer therapy or radiation therapy. Low potency topical steroid use is permitted. Topical bexarotene use is prohibited during the trial 7. Concomitant use of drugs with a risk of causing torsades des pointes 8. Concomitant us of CYP3A4/5 inhibitors 9. Patients with unresolved diarrhea > CTCAE grade 1 10. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption or oral LBH589 11. Other concurrent severe and/or uncontrolled medical conditions 12. Patients who would need to receive valproic acid for any reason during the study or ≥5 days prior to starting study drug 12. 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 14. Less than 3 months since prior electron beam therapy 15. Patients who have received wide field radiotherapy ≤4 weeks or limited field radiation for palliation ≤2 weeks prior to starting study drug or who have not recovered from side effects of such therapy Patients who have received biologic therapy, target therapy, vaccine, steroids or immunotherapy ≤2 weeks prior to starting study drug or who have not recovered from side effects of such therapy 16. Women who are pregnant or breast feeding or women of childbearing potnetial (WOCBP) not willing to use a double barrier 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. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test at baseline. 17. 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 must be a condom. |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Efficacy - Response rate
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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.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
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 |
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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 |