E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Cutaneous T cell lymphoma |
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E.1.1.1 | Medical condition in easily understood language |
Cutaneous T cell lymphoma (CTCL) is a rare malignant tumor of T lymphocytes, a subgroup of white blood cells. It can involve blood, skin and lymph nodes. So far, the disease is not yet curable. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028508 |
E.1.2 | Term | Mycosis fungoides/Sezary syndrome |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of the trial is to evaluate safety and efficacy of DMF treatment in patients with CTCL stage ≥Ib according to EORTC-ISCL consensus classification. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives of the study will be:
• To determine effects of DMF on the systemic CTCL involvement using the established CTCL severity index/modified severity assessment tool (mSWAT)19,20
• Effects of DMF on life quality of CTCL patients using the well-established dermatologic life quality index (DLQI)21
• Effects of DMF on pruritus and sensations of “burning pain” measured by a visual analog scales (VAS)
• DMF effect on immunologic and morphologic blood involvement if applicable using FACS
• changes in immunologic and cell death markers in skin samples of the patients using histologic, immune histologic and molecular biological methods
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Histopathologically confirmed Mycosis fungoides or Sézary syndrome (CTCL stage ≥ Ib according to EORTC-ISCL consensus classification2) at study entry with progressive, persistant or recurrent disease
• Pretreatment with topical steroid and/or local PUVA, if the prior therapy is not possible anymore or if there is unsatisfactory response to PUVA or local steroid respectively. Patients with history of first line systemic treatment (interferone or bexarotene) may be included in the study too
• Karnofsky index ≥70 % (according to Karnofsky DA, Burchenal JH. (1949). "The Clinical Evaluation of Chemotherapeutic Agents in Cancer." In: MacLeod CM (Ed), Evaluation of Chemotherapeutic Agents. Columbia Univ Press. Page 196)
• Life expectancy > 3 months
• Age ≥ 18 years
• Adequate organ function:
• differential blood count: hemoglobin ≥ 10 g/dl without transfusions, leukocyte count > 3000/µl, lymphocyte count > 700/µl
• liver enzymes ≤ 2 x upper limit of normal (ULN)
• serum creatinine ≤ 1.5 mg/dl or calculate creatinine clearance ≥ 50 ml/min,
• Negative Pregnancy test from blood, agreement for efficient contraception in male and female patients unless infertility is documented (DMF is not approved during pregnancy)
• Ability to understand character and individual consequences of the clinical trial and to provide written informed consent to participate in the study
• written informed consent must be given according to ICH/GCP, and national/local regulations, before patient registration and prior to any study specific procedures.
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E.4 | Principal exclusion criteria |
• Another active malignant disease with the following exceptions:
• Basal or squamous cell carcinoma of the skin
• In situ carcinoma of the cervix or the skin
• Topical chemotherapy, superficial radiotherapy, photopheresis or systemic CTCL treatment within 28 days before study therapy initiation
• Severe systemic disease or infection at study therapy initiation
• Prior treatment with DMF or simultaneous topical DMF treatment
• Contraindications for treatment with DMF (known hypersensibility to the drug, severe gastrointestinal disease (like ulcerations), Alcohol abuse, other obligately liver- or nephrotoxic medication, known clinically apparent renal or hepatic insufficiency)
• Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
• Participation in other clinical studies within 14 days before study therapy initiation
• Pregnant or lactating patients
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoint of the study will be the response rate of patients to DMF treatment. Practically this will be assessed by evaluating the eventual change in modified Severity Weighted Assessment (mSWAT) after an oral DMF treatment period of 24 weeks |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Secondary endpoints will be changes in CTCL severity index, influence of DMF therapy on DLQI, pruritus and pain as well as effects of DMF treatment on blood involvement if applicable. (In patients with stage IV disease the CD4/CD8 ratio and the number of circulating Sézary cells will be monitored.) In addition changes in immunologic and cell death markers in the skin of treated patients will be a secondary endpoint |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
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 | Yes |
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.8.2.4 | Number of treatment arms in the trial | 1 |
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 | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |