Cutaneous T-Cell Lymphoma (CTCL) has a chronic, relapsing course with patients undergoing multiple, consecutive therapies. Treatment aims at the clearance of skin disease, minimization of recurrence, prevention of disease progression and preservation of quality of life.
The treatment of CTCL is primarily determined by the disease extent. Prolonged complete remissions have been obtained with skin-directed therapies in early stage Mycosis fungoides (MF) (IA-IIA), whereas advanced stages CTCL (IIB-IVB) are often refractory to treatment and, thus, have an unfavorable prognosis.
Currently, there is no standard treatment option for CTCL, especially for advanced stages, and the optimal treatment sequence is still debated with a large variability in the therapeutic approach across countries. Patients with advanced-stage disease or refractory cutaneous CTCL should be treated with systemic therapies and, whenever possible, should be offered to participate in clinical trials. Currently, there is a urgent call for new treatments in CTCL with higher response rate and prolonged time to progression;
In this study, we propose a very innovative treatment schedule in which mogamulizumab is used before Total Skin Electron Beam therapy (TSEB) for systemic disease control and as a maintenance treatment after skin-directed therapy. We hypothesize that our regimen will show a more manageable toxicity profile than a combination treatment and allow for a long-term mogamulizumab administration.
Diagnosis of MF stage IB, IIA or IIB at registration, and MF stage should have never met criteria for stage IIIA or higher.
Subjects who have failed (refractory or relapsed) at least one prior course of systemic therapy.
All clinically significant toxic effects of prior cancer therapy to grade ≤ 1 according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE, v.5.0), excluding the specifications required in the criteria 'Adequate haematological and organ function' below
Males and female subjects ≥ 18 years
Prior treatment with mogamulizumab, or any other anti-CCR4
Prior TSEB
Patients who received localised radiotherapy within 2 weeks prior to registration
Patients who received any systemic therapy for MF within 4 weeks prior to registration.
Single group
Mogamulizumab
Drug• Patients will receive mogamulizumab 1.0 mg/kg IV over at least 1 hour on Days 1, 8, 15 and 22 of the first 28 day treatment cycle (C1) and on Days 1 and 15 of subsequent 28 day cycle (C2).
Total Skin Electron Beam Therapy (TSEB)
Radiation* After completion of C2, patients will be administered TSEB at a dose of 12 Gy in 8 fractions (4 fractions per week). TSEB will start 28 days (window of + 7 days) after mogamulizumab (C2 D1). * In case of toxicity from mogamulizumab, the maximum delay permitted for the start of TSEB is 2 weeks. * If recovery to at least grade 1 from toxicity exceeds the 2 weeks interval, please contact the medical monitor. * Mogamulizumab is stopped during TSEB administration.
Mogamulizumab (subsequent cycles post TSEB)
Drug• Mogamulizumab will be restarted at a dose of 1.0 mg/kg IV on Days 1, 8, 15 and 22 for cycle 3. Subsequent cycles will be administered as for C2. Treatment with mogamulizumab will be continued until disease progression (PD) or the occurrence of another withdrawal criterion.
Progression Free Survival Rate at 48 weeks
The primary endpoint is the progression free survival rate, assessed at 48 weeks after start of mogamulizumab
Occurrence of Adverse Events
Response rate to both mogamulizumab and TSEB
Proportion of patients achieving partial response or complete response according to EORTC-ISCL-USCLC criteria
Progression-free survival
From start of mogamulizumab to the first date of progressive disease or death from any cause
Overall survival
Start of mogamulizumab till the date of death from any cause
Quality of life using the Skindex-29 questionnaire
The Skindex-29 is a skin disease-specific questionnaire that comprehensively assesses the effects of skin diseases on patient's quality of life
Quality of life using the EORTC-QLQ-C30 questionnaire
Quality of Life will be assessed by using the EORTC-QLQ-C30 questionnaire
Click on the lead sponsor to view all of their trials.
