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

• ClinicalTrials.gov Identifier: NCT04128072
• Recruitment Status: Recruiting
• First Posted: October 16, 2019
• Last Update Posted: April 5, 2024
• Sponsor: European Organisation for Research and Treatment of Cancer - EORTC
• Information provided by (Responsible Party): European Organisation for Research and Treatment of Cancer - EORTC

Tracking Information

• First Submitted Date: October 14, 2019
• First Posted Date: October 16, 2019
• Last Update Posted Date: April 5, 2024
• Actual Study Start Date: March 7, 2023
• Estimated Primary Completion Date: October 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 29, 2020)

Progression Free Survival Rate at 48 weeks [ Time Frame: Up to 48 weeks after start of mogamulizumab for each patient ]

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

• Original Primary Outcome Measures (submitted: October 14, 2019): Progression Free Survival Rate [ Time Frame: 48 months after last patient in ]

Current Secondary Outcome Measures (submitted: September 1, 2020)

• Occurrence of Adverse Events [ Time Frame: 48 months after last patient in ]
• Response rate to both mogamulizumab and TSEB [ Time Frame: From the first patient treatment start till 48 weeks as of last patient in ]
  Proportion of patients achieving partial response or complete response according to EORTC-ISCL-USCLC criteria
• Progression-free survival [ Time Frame: From the first patient treatment start till 48 weeks as of last patient in ]
  From start of mogamulizumab to the first date of progressive disease or death from any cause
• Overall survival [ Time Frame: From the first patient treatment start till 5 years after last patient treatment ]
  Start of mogamulizumab till the date of death from any cause
• Time to progression [ Time Frame: From the first patient treatment start till 48 weeks as of last patient in ]
  From start of mogamulizumab to the date of first documentation of progressive disease or death due to progressive disease, whichever occurs first
• Duration of response [ Time Frame: From the first patient treatment start till 48 weeks as of last patient in ]
  Duration of response will be measured for patients achieving a partial response or complete response are first met until the first date that recurrent or progressive disease
• Time to next treatment [ Time Frame: From the first patient treatment start till 48 weeks as of last patient in ]
  From time from initiation of mogamulizumab until the time the initiation of any total skin-equivalent treatment (topical treatment to >50% of body surface, phototherapy, second TSEB) or systemic treatment is recorded

• Original Secondary Outcome Measures (submitted: October 14, 2019): Occurrence of Adverse Events [ Time Frame: 48 months after last patient in ]

Current Other Pre-specified Outcome Measures (submitted: June 29, 2020)

• Quality of life using the Skindex-29 questionnaire [ Time Frame: 48 months after last patient in ]
  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 [ Time Frame: 48 months after last patient in ]
  Quality of Life will be assessed by using the EORTC-QLQ-C30 questionnaire

Original Other Pre-specified Outcome Measures (submitted: October 14, 2019)

• Response rate [ Time Frame: 48 months after last patient in ]
• Progression-free survival [ Time Frame: 48 months after last patient in ]
• Overall survival [ Time Frame: 48 months after last patient in ]
• Time to progression [ Time Frame: 48 months after last patient in ]
• Duration of response [ Time Frame: 48 months after last patient in ]
• Duration of clinical benefit [ Time Frame: 48 months after last patient in ]
• Quality of life using the Skindex-29 questionnaire [ Time Frame: 48 months after last patient in ]
  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 [ Time Frame: 48 months after last patient in ]
  Quality of Life will be assessed by using the EORTC-QLQ-C30 questionnaire

Descriptive Information

• Brief Title: Anti-CCR4 Monoclonal Antibody (Mogamulizumab) and Total Skin Electron Beam Therapy (TSEB) in Patients With Stage IB-IIB Cutaneous T-Cell Lymphoma
• Official Title: MOGAT: Open-Label, Phase II, Multi-Centre, Study of Anti-CCR4 Monoclonal Antibody (Mogamulizumab) and Total Skin Electron Beam Therapy (TSEB) in Patients With Stage IB-IIB Cutaneous T-Cell Lymphoma

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Stage IB-IIB Cutaneous T-Cell Lymphoma

Intervention

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

  • 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.

Study Arms

Experimental: Mogamulizumab + Total Skin Electron Beam Therapy (TSEB)

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).

Interventions:

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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 14, 2019): 43
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: January 2027
• Estimated Primary Completion Date: October 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• 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.
• Male subjects and their female partners of child bearing potential must be willing to use an appropriate method of contraception defined as oral contraceptives, double barrier method (condom plus spermicide or diaphragm plus spermicide) or practice through abstinence from sexual intercourse (periodic abstinence, e.g., calendar, ovulation, symptothermal, post-ovulation methods and withdrawal are not acceptable methods of contraception) during the study and for 6 months after the last dose.
• Female subjects who are breast feeding should discontinue nursing prior to the first dose of study treatment and until 6 months after the last study treatment
• Before patient registration, written informed consent must be given according to ICH/GCP, and national/local regulations

Exclusion Criteria:

• 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
• Patients with a history of autoimmune-related hypothyroidism who are on thyroid replacement hormone are eligible for the study.
• Patients with eczema, psoriasis, lichen simplex chronicus, with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:
• Rash must cover <10% of body surface area
• Disease is well controlled at baseline and requires stable use of low to mild potency topical corticosteroids for at least 4 weeks.
• No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high potency or oral corticosteroids within the previous 4 months.
• Immunomodulatory drugs or high-dose systemic steroids for concomitant or intercurrent conditions other than T-cell lymphoma within 7 days of registration.

However, stable dose of a low dose systemic systemic corticosteroid (≤10 mg prednisone equivalent per day) or stable dose of a low potency topical corticosteroid for at least 4 weeks prior to the registration is permitted. Subjects may receive intra-articular, intraocular, inhalation or nasal corticosteroids. Initiation of treatment with corticosteroids or increase in dose while on study is not permitted except for the treatment of adverse events.

• Patients who are planned to receive stem cell transplantation
• Has a known history of Human T-lymphotropic virus 1 (HTLV-1), or human immunodeficiency virus (HIV) (test to be performed within 21 days of registration if allowed by local legislation)
• Has known active Hepatitis B or Hepatitis C
• Note: patient will be eligible if:
• Negative hepatitis B surface antigen (HBsAg) test at screening
• Negative total hepatitis B core antibody (HBcAb) test at screening, or positive total HBcAb test followed by a negative hepatitis B virus (HBV) DNA test at screening . The HBV DNA test will be performed only for patients who have a positive total HBcAb test.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation
• 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: EORTC EORTC HQ; +32 2 774 1611; eortc@eortc.org

• Listed Location Countries: Denmark, France, Germany, Greece, Italy, Spain, United Kingdom

Administrative Information

• NCT Number: NCT04128072
• Other Study ID Numbers: EORTC-1820-CLTF
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
• Original Responsible Party: Same as current
• Current Study Sponsor: European Organisation for Research and Treatment of Cancer - EORTC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: 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

• PRS Account: European Organisation for Research and Treatment of Cancer - EORTC
• Verification Date: April 2024