Anti-CCR4 Monoclonal Antibody (Mogamulizumab) and Total Skin Electron Beam Therapy (TSEB) in Patients With Stage IB-IIB Cutaneous T-Cell Lymphoma

NCT04128072 | Recruiting Phase 2 DMC

• 1 other identifier: EORTC-1820-CLTF
• Study Type: interventional
• Target: 43
• Locations: 7 countries
• Sites: 13

Brief Summary

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.

Conditions

Stage IB-IIB Cutaneous T-Cell Lymphoma

Keywords

Cutaneous T-Cell Lymphoma; Mogamulizumab; Total Skin Electron Beam therapy

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival Rate at 48 weeks

  The primary endpoint is the progression free survival rate, assessed at 48 weeks after start of mogamulizumab

  Up to 48 weeks after start of mogamulizumab for each patient

Secondary Outcomes (7)

• Occurrence of Adverse Events

  48 months after last patient in

• Response rate to both mogamulizumab and TSEB

  From the first patient treatment start till 48 weeks as of last patient in

• Progression-free survival

  From the first patient treatment start till 48 weeks as of last patient in

• Overall survival

  From the first patient treatment start till 5 years after last patient treatment

• Time to progression

  From the first patient treatment start till 48 weeks as of last patient in

Other Outcomes (2)

• Quality of life using the Skindex-29 questionnaire

  48 months after last patient in

• Quality of life using the EORTC-QLQ-C30 questionnaire

  48 months after last patient in

Study Arms (1)

Mogamulizumab + Total Skin Electron Beam Therapy (TSEB)

EXPERIMENTAL

Treatment with mogamulizumab will be continued until disease progression or the occurrence of another withdrawal criterion as specified in the protocol. TSEB will start 28 days after mogamulizumab cycle 2 day 1 at a dose of 12 Gy in 8 fractions over two weeks (4 fractions per week).

Drug: Mogamulizumab; Radiation: Total Skin Electron Beam Therapy (TSEB); Drug: Mogamulizumab (subsequent cycles post TSEB)

Interventions

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).

Mogamulizumab + Total Skin Electron Beam Therapy (TSEB)

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 + Total Skin Electron Beam Therapy (TSEB)

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.

Mogamulizumab + Total Skin Electron Beam Therapy (TSEB)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• WHO performance status 0-1
• Adequate haematological and organ function:
• absolute neutrophil count (ANC) ≥ 1.0 × 109/L
• platelets ≥ 75 × 109/L (≥ 75,000/mm3)
• bilirubin ≤ 1.5 × upper limit of normal (ULN) except for subjects with Gilbert's syndrome;
• aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 × ULN
• serum creatinine ≤ 1.5 × ULN or calculated creatinine clearance \> 50 mL/min using the Cockcroft-Gault formula
• Subjects previously treated with anti-CD4 antibody or alemtuzumab are eligible provided a washout period ≥ 3 months and CD4+ cell counts ≥ 200/mm3
• Clinically normal cardiac function based on 12-lead ECG and above the institutional lower limit of normal for left ventricular ejection fraction assessed either by multi-gated acquisition scan or cardiac ultrasound
• Women of child bearing potential (WOCBP) must have a negative serum pregnancy test within 3 days prior to the first dose of study treatment
• WOCBP must agree to use effective contraception, defined as oral contraceptives, double barrier method (condom plus spermicide or diaphragm plus spermicide) or practice through abstinence from sexual intercourse during the study and for 6 months after the last dose.

You may not qualify if:

• 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.
• Note: In case of rapid progression, if patient has recovered from all toxicities AND last dose occurred more than 5 half lives of the drug/treatment used, patient could be allowed to start earlier after consultation with medical monitor
• History of other malignancy in the past 5 years with the exception of treated carcinoma in situ of the cervix, localized prostate cancer with PSA \<0.1, in-situ melanoma, and non-melanoma skin cancer
• History of severe allergic anaphylactic reactions to chimeric, human or humanized antibodies, or fusion proteins
• Known hypersensitivity to CHO cell products or any component of the mogamulizumab formulation (see section 6.1.1)
• Significant uncontrolled intercurrent illness including, but not limited to:
• uncontrolled infection requiring antibiotics;
• clinically significant cardiac disease (class III or IV of the New York Heart Association \[NYHA\] classification);
• unstable angina pectoris;
• angioplasty, stenting, or myocardial infarction within 6 months;
• clinically significant cardiac arrhythmia
• Have active sign of herpes zoster

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead

Study Sites (13)

University Hospitals Copenhagen - Rigshospitalet

Copenhagen, 2100, Denmark

RECRUITING

CHU de Bordeaux - Groupe Hospitalier Saint-Andre - Hopital Saint-Andre

Bordeaux, 33075, France

RECRUITING

Assistance Publique Hopitaux Paris- APHP Nord - Univ De Paris Cite - Hop. Saint Louis

Paris, 75010, France

RECRUITING

UniversitaetsMedizin Mannheim

Mannheim, 68167, Germany

RECRUITING

Muehlenkreiskliniken Johannes Wesling Klinikum Minden

Minden, 32429, Germany

RECRUITING

Athens University - Attikon University General Hospital

Athens, 12462, Greece

RECRUITING

Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia

Brescia, 25123, Italy

RECRUITING

Azienda Ospedaliera Città della Salute e della Scienza di Torino - Ospedale San Lazzaro

Torino, 10126, Italy

RECRUITING

Hospital De La Santa Creu I Sant Pau

Barcelona, 08041, Spain

RECRUITING

Hospital Universitario 12 De Octubre

Madrid, 28041, Spain

RECRUITING

Hospital Universitario Puerta De Hierro

Madrid, 28222, Spain

RECRUITING

University Hospitals Birmingham NHS Foundation Trust (UHB) -Queen Elizabeth Medical Centre

Birmingham, B15 2TH, United Kingdom

RECRUITING

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

RECRUITING

MeSH Terms

Conditions

Lymphoma, T-Cell, Cutaneous

Interventions

mogamulizumab

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Pablo Luis Ortiz Romero

  Hospital Universitario 12 De Octubre,Madrid, Spain

  PRINCIPAL INVESTIGATOR

• Richard Cowan

  The Christie NHS Foundation Trust Manchester, UK

  PRINCIPAL INVESTIGATOR

• Jan Nicolay

  UniversitaetsMedizin Mannheim, Mannheim, Germany

  PRINCIPAL INVESTIGATOR

Central Study Contacts

EORTC EORTC HQ

CONTACT

+32 2 774 1611; eortc@eortc.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 14, 2019
• First Posted: October 16, 2019
• Study Start: March 7, 2023
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): January 1, 2027
• Last Updated: April 5, 2024

Record last verified: 2024-04

Locations

ES (3); DK (1); FR (2); GR (1); IT (2); GB (2); DE (2)