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

Inclusion Criteria:

• Diagnosis of MF stage IB, IIA or IIB at registration, and MF stage should have nevermet criteria for stage IIIA or higher.
• Subjects who have failed (refractory or relapsed) at least one prior course ofsystemic therapy.
• All clinically significant toxic effects of prior cancer therapy to grade ≤ 1according to the National Cancer Institute Common Terminology Criteria for AdverseEvents version 5.0 (NCI-CTCAE, v.5.0), excluding the specifications required in thecriteria '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'ssyndrome;
• aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 × ULN
• serum creatinine ≤ 1.5 × ULN or calculated creatinine clearance > 50 mL/min using theCockcroft-Gault formula
• Subjects previously treated with anti-CD4 antibody or alemtuzumab are eligibleprovided a washout period ≥ 3 months and CD4+ cell counts ≥ 200/mm3
• Clinically normal cardiac function based on 12-lead ECG and above the institutionallower limit of normal for left ventricular ejection fraction assessed either bymulti-gated acquisition scan or cardiac ultrasound
• Women of child bearing potential (WOCBP) must have a negative serum pregnancy testwithin 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) orpractice through abstinence from sexual intercourse during the study and for 6 monthsafter the last dose.
• Male subjects and their female partners of child bearing potential must be willing touse an appropriate method of contraception defined as oral contraceptives, doublebarrier method (condom plus spermicide or diaphragm plus spermicide) or practicethrough abstinence from sexual intercourse (periodic abstinence, e.g., calendar,ovulation, symptothermal, post-ovulation methods and withdrawal are not acceptablemethods 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 firstdose of study treatment and until 6 months after the last study treatment
• Before patient registration, written informed consent must be given according toICH/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 toregistration. Note: In case of rapid progression, if patient has recovered from all toxicities AND lastdose occurred more than 5 half lives of the drug/treatment used, patient could be allowedto start earlier after consultation with medical monitor
• History of other malignancy in the past 5 years with the exception of treatedcarcinoma in situ of the cervix, localized prostate cancer with PSA <0.1, in-situmelanoma, and non-melanoma skin cancer
• History of severe allergic anaphylactic reactions to chimeric, human or humanizedantibodies, or fusion proteins
• Known hypersensitivity to CHO cell products or any component of the mogamulizumabformulation (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 HeartAssociation [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 thyroidreplacement hormone are eligible for the study.
• Patients with eczema, psoriasis, lichen simplex chronicus, with dermatologicmanifestations only (e.g., patients with psoriatic arthritis are excluded) areeligible 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 potencytopical corticosteroids for at least 4 weeks.
• No occurrence of acute exacerbations of the underlying condition requiring psoralenplus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oralcalcineurin inhibitors, or high potency or oral corticosteroids within the previous 4months.
• Immunomodulatory drugs or high-dose systemic steroids for concomitant or intercurrentconditions other than T-cell lymphoma within 7 days of registration. However, stable dose of a low dose systemic systemic corticosteroid (≤10 mg prednisoneequivalent per day) or stable dose of a low potency topical corticosteroid for at least 4weeks prior to the registration is permitted. Subjects may receive intra-articular,intraocular, inhalation or nasal corticosteroids. Initiation of treatment withcorticosteroids or increase in dose while on study is not permitted except for thetreatment 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 humanimmunodeficiency virus (HIV) (test to be performed within 21 days of registration ifallowed 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 totalHBcAb test followed by a negative hepatitis B virus (HBV) DNA test at screening . TheHBV 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 abnormalitythat might confound the results of the trial, interfere with the subject'sparticipation
• Any psychological, familial, sociological or geographical condition potentiallyhampering compliance with the study protocol and follow-up schedule; those conditionsshould be discussed with the patient before registration in the trial