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

Cutaneous T Cell Lymphoma Clinical Trial

— DMF-CTCL  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02546440
• Other study ID #: EudraCT-Number: 2014-000924-11
• Status: Completed
• Phase: Phase 2
• Start date: September 2015
• Est. completion date: September 2022

Study information

• Verified date: March 2023
• Source: Universitätsmedizin Mannheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: September 2022
• Est. primary completion date: September 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cutaneous T Cell Lymphoma
• Lymphoma
• Lymphoma, T-Cell
• Lymphoma, T-Cell, Cutaneous
• Lymphoma, T-Cell, Peripheral

Intervention

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

Locations

Country	Name	City	State
Germany	University Medical Center	Mannheim

Sponsors (7)

Lead Sponsor	Collaborator
Universitätsmedizin Mannheim	KKS Netzwerk, Klinikum Krefeld, Klinikum Ludwigshafen, Klinikum Minden, Universitätsklinikum Kiel, Wuerzburg University Hospital

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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