E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary cutaneous lymphomas are non-Hodgkin lymphomas that present to the skin without evidence of extracutaneous disease at the time of diagnosis. It refers to either to cutaneous T-cell lymphoma (CTCL) or cutaneous B-cell lymphoma (CBCL). The primary cutaneous lymphomas are classified according to the WHO-EORTC classification. CTCL constitutes about 65% of all primary cutaneous lymphomas, of which mycosis fungoides is the most prevalent clinical presentation. |
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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 | PT |
E.1.2 | Classification code | 10028483 |
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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 anti-tumor activity of APO866 in ppatients with relapsed or refractory CTCL |
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E.2.2 | Secondary objectives of the trial |
To determine the safety and tolerability of APO866 in this population To determine the effect of APO866 on the time to response, response duration and time to treatment failure.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
To be eligible for inclusion into this study, the patients must fulfil all of the following criteria: Histologically confirmed diagnosis of CTCL including mycosis fungoides and Sézary syndrome or others according the WHO/EORTC classification18 Stage Ib to IVb disease (AJCC TNM staging) Relapsed or refractory disease or intolerant to ≥ 2 prior systemic therapy. PUVA, topical nitrogen mustard, spot or total skin electron beam therapy or other radiotherapy, oral retinoids, immunotherapy (e.g. interferon-a, denileukin difitox, alemtuzumab) or mono- or poly-chemotherapy regimen will be considered systemic therapy. ECOG performance status < 2 Age > 18 years, of either sex. Have given written informed consent, prior to any study related procedure not part of the patient’s normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
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E.4 | Principal exclusion criteria |
To be eligible for inclusion in this study the patients must not meet any of the following criteria: Have participated in any other investigational study or received an experimental therapeutic procedure considered to interfere with the study in the 2 months preceding SD1 Have had PUVA, topical nitrogen mustard, spot or total skin electron beam therapy, oral retinoids, or any, immunotherapy (e.g. interferon-a, denileukin difitox, alemtuzumab) or chemotherapy regimen within 2 weeks of SD1. Patients must have recovered of all acute toxicities. Evidence of CNS lymphoma Use of concomitant prohibited medication due to CYP3A4 metabolism of APO866 Use of bisphosphonate drugs during the 30 days preceding the APO866 perfusion Uncontrolled medical conditions, requiring surgical or pharmacological treatment (exceptions must be approved by the Study Director). Serious concomitant disease (e.g. significant cardiac disease) are not eligible Primary or acquired thrombocytopenia Inadequate bone marrow reserve: WBC < 3.5x109/L, neutrophils < 1.0x109/L, thrombocytes < 100x109/L, Hb < 8.5 g/dL or coagulation abnormalities Inadequate liver function: total bilirubin > 1.5 x upper limit of normal values (ULN), AST, ALT, or alkaline phosphatase > 2.5 x ULN Have inadequate renal function, defined by serum creatinine > 250 mmol/L Retinopathy, history of retinal laser surgery, or in the case of abnormal results on either of the corrected visual acuity color vision, threshold visual field, Amsler grid and fundus oculi tests, an ERG < 50% of normal Pregnant or breastfeeding. Female patients with child-bearing potential must be using a hormonal contraceptive, intra-uterine device, diaphragm with spermicide or condom with spermicide for the duration of the study. Women of childbearing potential must have a negative serum or urinary hCG pregnancy test. Females whom are surgically sterile or post-menopausal are eligible for the study.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is defined as the proportion of patients with refractory or relapsed CTCL whom meet the following conditions: fullfil all eligibility criteria have had at least 1 cycle of APO866 have a complete clinical response (CCR) or partial response (PR) as defined by the response criteria in the protocol
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
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 | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
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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For administrative and safety reporting purposes the end of the study will be defined as the date of the final clinical database lock. This provides for a single and conservative definition across all study sites. |
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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 | |
E.8.9.1 | In the Member State concerned months | 18 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 18 |