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

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

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.

Study Overview

• Status: Completed
• Conditions: Cutaneous T Cell Lymphoma
• Intervention / Treatment: Drug: Dimethyl fumarate

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jan P Nicolay, MD; Phone Number: 00496213832280; Email: jan.nicolay@umm.de
• Study Contact Backup: Name: Jochen Utikal, MD; Phone Number: 00496213832280; Email: jochen.utikal@umm.de

Study Locations

• Germany
  • Mannheim, Germany, 68167
    • University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: treatment arm; 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; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Universitätsmedizin Mannheim
• Collaborators: Klinikum Ludwigshafen; Wuerzburg University Hospital; KKS Netzwerk; Klinikum Minden; Klinikum Krefeld; Universitätsklinikum Kiel

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2015
• Primary Completion (Actual): September 1, 2021
• Study Completion (Actual): September 1, 2022

Study Registration Dates

• First Submitted: September 6, 2015
• First Submitted That Met QC Criteria: September 9, 2015
• First Posted (Estimate): September 10, 2015

Study Record Updates

• Last Update Posted (Actual): March 31, 2023
• Last Update Submitted That Met QC Criteria: March 28, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Lymphoma, T-Cell, Cutaneous; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Dimethyl Fumarate
• Other Study ID Numbers: EudraCT-Number: 2014-000924-11