E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Cutaneous T-cell lymphoma: Mycosis Fungoides, Stage IIB to IV or Sézary Syndrome |
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E.1.1.1 | Medical condition in easily understood language |
Cutaneous T-cell lymphoma |
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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 | 14.1 |
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 | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The overall objective is to determine if maintenance treatment with lenalidomide prolongs response after debulking in patients with advanced stage CTCL who have not been previously treated with intravenous chemotherapy except the chemotherapy received in the preceeding debulking stage. Patients will be randomized to either receive the maintenance therapy or not, and these two study arms will be compared in terms of the difference in progression free survival (PFS). |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives assess: -overall survival; -progression free survival as assessed by hematogenous disease criteria (see chapter 7); -acute and late toxicity; -conversion rate; - and, rate of occurrence of second cancers at any site.
Additional secondary objectives are translational research-related and include: -to advance understanding of cutaneous T-cell lymphoma itself, as well as its response to treatment with maintenance lenalidomide; -to allow collection and storage of biological material from patients enrolled in this study for use in future translational research studies |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
♦ Advanced stage mycosis fungoides (stage IIB-IV), or Sézary Syndrome. ♦ Prior debulking therapy with either mono-chemotherapy, Poly-chemotherapy/combination chemo and radiotherapy or radiotherapy alone (e.g. Total Skin Electron Beam body radiation [TSEB]) (according to local institutional guidelines) resulting in complete or partial response as defined in this protocol's "Evaluation criteria" chapter. At the time of registration, patients provide consent for the collection of this pre/post debulking assessment information. ♦ For patients with Sézary syndrome, Sézary cell burden has to be decreased by at least 50 percent after debulking. ♦ Local low-dose/energy ionizing radiation therapy may be used as part of the debulking process in combination with chemotherapy. ♦ High dose steroids may be used as part of the debulking regimen as per local institution protocols, but must have been discontinued by the end of debulking and at the time of disease response assessment. ♦ Disease not appropriate for skin-directed therapy, per local institution standards. ♦ Disease not previously treated with intravenous anti-neoplastic agents (except for the debulking agents, used for that purpose immediately prior to this protocol). ♦ Age > 18 years. ♦ WHO performance status 0-2. ♦ Life expectance greater than 12 months. ♦ Patients with high risk for or history of a thromboembolic event must agree to receive prophylactic anti-coagulation therapy to keep the International normalized ratio (INR) in the range of 2-3. ♦ No second malignancies in the 3 years prior to study entry with the exception of surgically cured carcinoma in situ of the cervix, in situ breast cancer, incidental finding of stage T1a or T1b prostate cancer, and basal/squamous cell carcinoma of the skin. ♦ Female subjects of childbearing potential (as defined in the protocol) must agree to use an appropriate form of contraception, as defined in chapter 3 'Patient seclection criteria'. ♦ Male subjects must agree to use condoms throughout study drug therapy and follow guidelines, as described in chapter 3 'Patient seclection criteria'. ♦ Written informed consent must be given according to the International Conference on Harmonisation (ICH) Harmonized Tripartite Guideline on Good Clinical Practice (ICH/GCP), and national/local regulations. |
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E.4 | Principal exclusion criteria |
♦ Central nervous system involvement. ♦ Uncontrolled infectious disease, autoimmune disease, immunodeficiency, or history of either splenectomy or splenic irradiation. ♦ No pregnant or breast feeding subjects. ♦ No Lapp lactase deficiency or history of glucose-galactose malabsorption. ♦ Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression free (PF) survival (PFS) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Timepoint(s) of evaluation of the primary end point: "Progression-free survival (PFS)" Futility analysis based on PFS will take place at approximately 30 months after the first patient randomized. The final analysis will take place at approximately 62 months after the first patient randomized. The interim analysis (IA) will be conducted when 33.7% of information is available (30 events). Assuming the above accrual rate (2 pts/per month), the IA is expected to take place 27 months after the first patient randomized or around 51 patients accrued. The IA Report is confidential and will be reviewed by the IDMC which will make a recommendation to continue or stop the study based on the IA.
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E.5.2 | Secondary end point(s) |
Secondary endpoints include overall survival, PFS, acute and late toxicity, conversion rate, and rate of occurrence of second cancers at any site. Additionally, translational research objectives are: - To advance the understanding of cutaneous T-cell lymphoma itself, as well as its response to treatment with maintenance lenalidomide. - Allow the collection and storage of biological material from patients enrolled in this study for use in future translational research studies. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary endpoints will be analyzed at the same time as the primary endpoint analyses; this will be done whenever the study is mature for the primary endpoint analysis.
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
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 | Yes |
E.8.2.3.1 | Comparator description |
standard treatment strategy |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
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 | No |
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 |
Austria |
Belgium |
Denmark |
Finland |
France |
Netherlands |
Spain |
Switzerland |
United Kingdom |
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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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End of study occurs when all of the following criteria have been satisfied: 1. Thirty days after all patients have stopped protocol treatment. 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 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 | 7 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 7 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |