E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Early stage mycosis fungoides cutaneous T cell lymphoma (MF-CTCL) |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 22.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028483 |
E.1.2 | Term | Mycosis fungoides |
E.1.2 | System Organ Class | 100000004864 |
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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 |
The objective of the trial is to determine activity of the drug as measured by response rate in patients treated with chlormethine gel (CL gel) without skin drug reaction (Group A) and in patients treated with CL gel with skin drug reactions and subsequent reduced CL gel application frequency (Group B). |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives: • To determine activity of the drug as measured by response rate in patients treated with CL gel (overall population) • To determine the number of patients developing a skin reaction to CL gel and the percentage who are subsequently patch test positive • To determine the percentage of patients with skin drug reactions remaining on CL gel whether at reduced frequency, or co-administration of corticosteroids (Group B and C) • To determine time to occurrence of skin drug reaction, time to response, and duration of response • To determine Progression free survival (PFS) • To determine Time to Next Treatment (TTNT) Exploratory objectives: • To determine activity of the drug as measured by response rate in patients treated with CL gel with skin drug reactions, with subsequent reduced CL gel application and administration of topical corticosteroids (Group C) • To determine quality of life |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Diagnosis of MF-CTCL stage IA or IB at enrolment as per ISCL/EORTC revision to the MF and Sézary syndrome classification [3] and MF stage should have never met the criteria for stage IIA or higher in the patient medical history • Age ≥ 18 • ECOG/WHO performance status 0-2 • Lesions cover less than 80% of BSA • Women of child bearing potential (WOCBP) must have a negative serum pregnancy test within 3 days prior to enrolment • WOCBP should use adequate birth control measures, during the study treatment period until 30 days after treatment. (See Appendix H). Male subjects who are partner of WOCBP should use condom during treatment. • Female subjects who are breast feeding should discontinue nursing prior to the first application of study treatment and until 30 days after the last study treatment • Before patient enrolment, written informed consent must be given according to ICH/GCP, and national/local regulations |
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E.4 | Principal exclusion criteria |
• Known hypersensitivity to any component of the Chlormethine gel formulation • Previous treatment with CL gel • Concurrent or planned local or systemic anti-CTCL therapy • Prior treatment with antihistamines or narrow band UV-B or PUVA therapy one week before enrolment, or systemic corticosteroids or radiotherapy in the last 4 weeks before enrolment • Prior treatment with topical steroids one week before enrolment • MF or other pathological skin lesions in the patch test area (upper back) • Acute flare of atopic dermatitis or other dermatosis in the last 3 weeks • Current or recent (past 6 months) history of severe or uncontrolled renal, hepatic, gastrointestinal, metabolic, endocrine, pulmonary, cardiovascular, or neurological disease. A severe disease is defined as a condition which is medically significant although not immediately life-threatening, requires urgent medical intervention, hospitalization or prolongation of hospitalization, is disabling and/or limiting self-care (bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden). All diseases classified as grade 3 or above according to CTCAE version 5.0 are severe conditions. • Prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of this investigational regimen, according to the investigator's opinion. • 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 enrolment in the trial • Protected persons, such as people with psychiatric, cognitive, or developmental disorders, and patients who are unconscious or critically ill, and in general all subjects with diminished capacity for judgment, reasoning and autonomous decision-making are not eligible for this trial. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint in this study is Overall response rate (ORR) defined as the proportion of patients who achieved a complete response (CR) or partial response (PR) within the first 56 weeks from start of treatment in in patients treated with chlormethine gel (CL gel) without skin drug reaction (Group A) and in patients treated with CL gel with skin drug reactions and subsequent reduced CL gel application frequency (Group B). The response needs to be longer than 8 weeks. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
ORR in Group A and in Group B is defined within a time frame for the response evaluation up to maximum 56 weeks starting from first use of the gel. The response should be confirmed within 8 weeks of the first date of response. |
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E.5.2 | Secondary end point(s) |
• Proportion of ORR in the overall population within the first 56 weeks from the start of the treatment • Proportion of patients with skin drug reactions remaining on CL gel whether at reduced frequency, or co-administration of corticosteroids. This endpoint is applicable to Group B and C • Frequency of occurrence of skin drug reaction •Time to occurrence of skin drug reaction • Time to response. • Duration of response. • Progression free survival (PFS) • Time to Next Treatment (TTNT) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
-ORR in the overall population defined within a time frame for response evaluation up to 56 wks starting from 1st gel use -Prop. of patients remaining on treatment (ttmt) in grp B & C defined within 56 wks from ttmt start -Freq. of occurrence of skin drug reaction defined within the first 56 wks from ttmt start -Time to occurrence of skin drug reaction, defined as time from ttmt start until time of occurrence of a skin drug reaction -Time to response defined from ttmt start to first occurrence of complete/partial response -Duration of response defined from first occurrence of complete/partial response to ttmt until disease progression -PFS defined from start of ttmt to disease progression or death from any cause -TTNT defined from start of ttmt until next one for mycosis fungoides |
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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 | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
• Biobanking • Quality of Life (QoL) |
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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
| 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 | 9 |
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 | Yes |
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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The end of trial occurs on the date of the last visit of the last patient undergoing the trial. End of study (when the trial database can be frozen for the primary data analysis) occurs when the following criteria have been satisfied: 1.Thirty days after all patients have stopped protocol treatment or reached the 56-week timepoint 2.The trial is mature for the analysis of the primary endpoint as defined in the protocol 3.The database has been fully cleaned and frozen for this analysis |
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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 | 6 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |