Study on Therapy With Dimethylfumarate (DMF) in Patients With Cutaneous T Cell Lymphoma (CTCL)

Study Overview
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Brief Summary
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The main objective of the trial is to investigate whether oral treatment of patients suffering from cutaneous T cell lymphoma with dimethylfumarate is leading to a significant improvement of modified severity assessment tool (mSWAT) values in the skin after 24 weeks of treatment (primary endpoint). Secondary endpoints are dermatologic life quality index, itching and pain measured by a NRS and the blood involvement if applicable. Primary: safety and efficacy of DMF treatment in CTCL Secondary: Dermatologic Life Quality index, NRS for itching and pain, blood involvement if appl.

Official Title
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Phase IIA Study on Therapy With the NF-κB Inhibiting and Apoptosis Inducing Drug Dimethylfumarate (DMF) in Patients With Cutaneous T Cell Lymphoma (CTCL)

Conditions
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Cutaneous T Cell Lymphoma

Intervention / Treatment
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* Drug: Dimethyl fumarate


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Histopathologically confirmed Mycosis fungoides or Sézary syndrome (CTCL stage ≥ Ib according to EORTC-ISCL consensus classification) at study entry with progressive, persistant or recurrent disease Pretreatment with at least one topical or systemic CTCL therapy or UV therapy, if the prior therapy is not possible anymore or if there is new contraindication or unsatisfactory response 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. 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: treatment arm<br>patients are treated with dimethylfumarate over 24 weeks. Dosage will be escalated weekly from 30 mg/d to 720 mg/d over 9 weeks. The dose escalation scheme is the same as approved for psoriasis treatment in Germany | Drug: Dimethyl fumarate<br>* dose escalation from 30 mg/d to maximally 720 mg/d over 9 weeks, then continuing with the highest tolerated dose following a preset design in psoriasis treatment in Germany, oral medication in tablet form. Treatment will last 24 weeks or until either progression or unacceptable side effects occur<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safety (via occurrence of AE/SAE) of DMF treatment in CTCL | Number of patients with Treatment-related Adverse Events as assessed by CTCAE v4.0 | every 2 weeks until 24 weeks of treatment are finished | 
| efficacy (via improvement of Skin involvement measured by the standardized modified severity weighted assessment tool (mSWAT))of DMF treatment in CTCL | Changes in the mSWAT scores range from 0 [no patches, Plaques or tumors on the Skin ] to 400 [complete Body covered by Tumors] | every 2 weeks until 24 weeks of treatment are finished | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| changes in dermatologic life quality index | Scores range from 0 [no restriction of life Quality] to 30 [maximal restriction of life Quality] | every 2 weeks until 24 weeks of treatment are finished | 
| changes in pruritus intensity measured by a visual analog scale | Scores range from 0 [no Pruritus] to 10 [worst possible Pruritus] | every 2 weeks until 24 weeks of treatment are finished | 
| changes in blood involvement measured by Sezary cell count (if applicable, only in stage IV patients) |  | every 2 weeks until 24 weeks of treatment are finished |