Overview

The purpose of the study is to evaluate the efficacy and safety of mogamulizumab (KW-0761) in chinese subjects with mycosis fungoides or sézary syndrome previously treated with systemic therapy

Eligibility

Inclusion Criteria:

1. Voluntarily signed and dated ethics committee (EC) approved informed consent form in accordance with regulatory and institutional guidelines. Written informed consent must be obtained prior to performing any study-related procedure.
2. Male and female Chinese subjects ≥18 years of age at the time that written informed consent is obtained.
3. Histologically confirmed diagnosis of MF or SS;
4. Stage IB, IIA, IIB, III, and IV.
5. Patients who have failed at least one prior systemic therapy. Systemic therapy includes, for example, interferon, denileukin diftitox, retinoid, photopheresis, anti-neoplastic chemotherapy, methotrexate, and Histone deacetylase (HDAC) inhibitor.
   • Ultraviolet light therapy (Psoralen plus ultraviolet A [PUVA], ultraviolet B [UVB] etc), systemic steroid monotherapy, topical steroid or other topical agents, and any radiation are not considered to be a systemic therapy.
6. Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 1.
7. The subject has resolution of all clinically significant toxic effects of prior cancer therapy to Grade ≤ 1 by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI-CTCAE, ver. 5.0) excluding the specifications required in 8, 9, and 10 below.
8. Adequate hematological function:
   • absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L;
   • platelets ≥ 100.0 × 10^9/L;
   • in subjects with known bone marrow involvement, ANC must be ≥ 1.0 × 10^9/L and platelets ≥ 75.0 × 10^9/L.
9. Adequate hepatic function:
   • Total bilirubin ≤ 1.5 times the specific institutional upper limit of normal (ULN);
   • aspartate transaminase (AST) and alanine transaminase (ALT) each ≤ 2.5 × ULN or ≤ 5.0 × ULN in the presence of known hepatic involvement by CTCL.
10. Adequate renal function:
    • serum creatinine (SCr) ≤ 1.5 × ULN, or calculated creatinine clearance (CCr)> 50 mL/min using the Cockcroft-Gault formula.

(CCr={((140-age) × body weight)/(72 × SCr)} × 0.85 (if female))

         11. Patients with MF and a known history of non-complicated staphylococcus
             infection/colonization are eligible provided they continue to receive stable doses of
             prophylactic antibiotics.
         12. Women of childbearing potential must have a negative pregnancy test within 7 days
             prior to receiving study medication.
         13. Women of childbearing potential (WOCBP)* and fertile men who consent to practice
             contraception using highly effective methods during a period from the day providing
             her consent to the end of the study (for women) or from the start of IP administration
             to the end of the study (for men). WOCBP shall have a negative pregnancy test result
             in the screening examination and a negative pregnancy test result in the pre-dose
             examination at Day 1.
               -  WOCBP do not include women who underwent permanent contraception, postmenopausal
                  women (in the case of the absence of menstruation for 12 months or more
                  regardless of other medical reasons and serum follicle stimulating hormone (FSH)
                  level >40 mIU/mL) and women who are anatomically incapable of becoming pregnant.
        Exclusion Criteria:
          1. Current evidence of large cell transformation (LCT). Patients with clinical features
             suggestive of LCT are recommended to have a biopsy performed within 4 months prior to
             Cycle 1 Day 1 to rule out transformed disease. Patients with a history of LCT but
             without current aggressive disease and no current evidence of LCT on pathology in skin
             or lymph nodes are eligible.
          2. Diagnosed with a malignancy other than MF/SS in the past 2 years from the time that
             written informed consent is obtained. However, subjects with non-melanoma skin
             cancers, melanoma in situ, localized cancer of the prostate with current
             prostate-specific antigen of < 0.1 ng/mL, treated thyroid cancer or cervical carcinoma
             in situ, or ductal/lobular carcinoma in situ of the breast within the past 2 years may
             be enrolled as long as there is no current evidence of disease.
          3. Clinical evidence of central nervous system metastasis.
          4. Psychiatric illness, disability or social situation that would compromise the
             subject's safety or ability to provide consent, or limit compliance with study
             requirements.
          5. 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;
               -  uncontrolled hypertension (systolic blood pressure [BP] > 160 mmHg or diastolic
                  BP>100 mmHg, found on 2 consecutive measurements separated by a 1-week period)
                  despite 2 antihypertensive medications;
               -  clinically significant cardiac arrhythmia;
               -  uncontrolled diabetes.
          6. Known or tests positive for human immunodeficiency virus (HIV) or history of HIV
             infection, or hepatitis C disease or history of hepatitis C infection.
          7. Tests positive for hepatitis B virus surface (HBs) antigen or both HBc antibody and
             hepatitis B virus (HBV)-DNA positive (over the lower limit of quantification);
             - Patients with HBs antibody positive due to a hepatitis B vaccine will be allowed to
             participate in this trial.
          8. Active herpes simplex or herpes zoster. Patients on prophylaxis for herpes who started
             taking medication at least 30 days prior to the pretreatment visit, have no signs of
             active infection, and whose last active infection was more than 6 months ago may enter
             the study, and should continue to take the prescribed medication for the duration of
             the study.
          9. Experienced allergic reactions to monoclonal antibodies or other therapeutic proteins.
         10. Known active autoimmune disease (e.g., Graves' disease; systemic lupus erythematosus;
             rheumatoid arthritis; Crohn's disease; psoriasis).
         11. Is pregnant (confirmed by beta human chorionic gonadotrophin [β-HCG]) or lactating.
         12. Prior treatment with mogamulizumab.
         13. Have had any therapy directed against the subject's underlying cancer or any
             investigational medications within 4 weeks of registration (skin directed treatments,
             including topicals and radiation within 2 weeks of registration treatment).
         14. Subjects on a stable dose of a low dose systemic corticosteroid (≤ 20 mg prednisone
             equivalent) for at least 4 weeks prior to the registration may continue use although
             the investigator should attempt to taper the use to the lowest dosage tolerable while
             on study.
         15. Subjects on a stable dose of medium or low potency topical corticosteroids for at
             least 4 weeks prior to the registration may continue use at the same dose, although
             the investigator should attempt to taper the use to the lowest dosage tolerable while
             on study.
         16. History of allogeneic transplant.
         17. Autologous hematopoietic stem cell transplant within 90 days of the screening.
         18. Patients on any immunomodulatory drug for concomitant or intercurrent conditions or
             who have received any of these agents within 4 weeks of registration, including but
             not limited to the following, will be excluded: low-dose or oral methotrexate,
             azathioprine, iv immunoglobulin, low-dose or oral cyclophosphamide, cyclosporine,
             mycophenolate, infliximab, etanercept, leflunomide, adalimumab, lenalidomide,
             abatacept, rituximab, anakinra, interferon-β, interleukin-2, and natalizumab.
         19. Anyone otherwise considered unsuitable participation in the study by the investigator
             or subinvestigator.