Study of KW-0761 Versus Vorinostat in Relapsed/Refractory CTCL
Condition: Cutaneous T-Cell Lymphoma
MeSH terms: Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Lymphoma, T-Cell, Cutaneous
Intervention: KW-0761; Vorinostat
Intervention description: 1.0 mg/kg weekly x 4 in cycle 1 then every other week until progression
Intervention MeSH terms: Vorinostat; Mogamulizumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 372.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Cutaneous T-Cell Lymphoma (CTCL); myocis fungoides (MF); Sezary Syndrome (SS)

Summary:

      The purpose of this study is to compare the progression free survival of KW-0761 versus
      vorinostat for subjects with relapsed or refractory CTCL.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male and female subjects ≥ 18 years of age at the time of enrollment, except in Japan
             where subjects must be ≥ 20 years of age at the time of enrollment

          -  Histologically confirmed diagnosis of mycosis fungoides (MF) or Sezary Syndrome (SS)

          -  Stage IB, II-A, II-B, III and IV

          -  Subjects who had failed at least one prior course of systemic therapy. Psoralen plus
             ultraviolet light therapy (PUVA) is not considered to be a systemic therapy

          -  Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 1 at study
             entry

          -  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 4.0 (NCI-CTCAE, v.4.0)

          -  Adequate hematological, renal and hepatic function

          -  Subjects previously treated with anti-CD4 antibody or alemtuzumab were eligible
             provided their CD4+ cell counts were ≥ 200/mm3

          -  Subjects with mycosis fungoides (MF) and a known history of non-complicated
             staphylococcus infection/colonization were eligible provided they continued to receive
             stable doses of prophylactic antibiotics

          -  Women of childbearing potential (WOCBP) must have had a negative pregnancy test within
             7 days of receiving study medication

          -  WOCBP and male subjects as well as their female partners of childbearing potential
             must have agreed to use effective contraception throughout the study and for 3 months
             after the last dose of KW-0761

        Exclusion Criteria:

          -  Prior treatment with KW-0761 or vorinostat.

          -  Large cell transformation. However, subjects with a history of LCT but without current
             aggressive disease and no current evidence of LCT on pathology in skin and lymph nodes
             would be eligible.

          -  Diagnosed with a malignancy in the past two years. However, subjects with non-melanoma
             skin cancers, melanoma in situ, localized cancer of the prostate with current PSA 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 two years could enroll as long as
             there was no current evidence of disease.

          -  Clinical evidence of central nervous system (CNS) metastasis.

          -  Psychiatric illness, disability or social situation that would have compromised the
             subject's safety or ability to provide consent, or limited compliance with study
             requirements.

          -  Significant uncontrolled intercurrent illness

          -  Known or tested positive for human immunodeficiency virus (HIV), human T-cell leukemia
             virus (HTLV-1), hepatitis B or hepatitis C.

          -  Active herpes simplex or herpes zoster. Subjects on prophylaxis for herpes who started
             taking medication at least 30 days prior to study entry, and had no active signs of
             active infection, and whose last active infection was more than 6 months ago, could
             enter the study, and should have continued to take the prescribed medication for the
             duration of the study.

          -  Experienced allergic reactions to monoclonal antibodies or other therapeutic proteins.

          -  Known active autoimmune disease were excluded. (For example, Grave's disease; systemic
             lupus erythematosus; rheumatoid arthritis; Crohn's disease; psoriasis).

          -  Was pregnant (confirmed by beta human chorionic gonadotrophin [β-HCG]) or lactating.

          -  History of allogeneic transplant.