KW-0761 or Investigator's Choice in Subjects With Previously Treated Adult T-cell Leukemia-Lymphoma (ATL)

CCR4 expression in ATL patients has been demonstrated to be very high and has been associated
with shorter survival compared with CCR4-negative patients. KW-0761, a monoclonal antibody
targeted to CCR4, has been shown to be safe and tolerable in several clinical trials in
subjects with a variety of T-cell malignancies, including ATL, mycosis fungoides and Sézary
syndrome. The objective of this study is to estimate the overall response rate of KW-0761 for
subjects with relapsed or refractory ATL.

Inclusion Criteria:

- Males and female subjects ≥ 18 years of age

- Confirmed diagnosis of ATL (excluding smoldering subtype)

- Subjects must currently have evidence of disease in at least one of the following:

- Lymph nodes

- Extranodal masses

- Spleen or liver

- Skin

- Peripheral blood

- Bone marrow

- Relapsed or refractory after at least one prior systemic therapy regimen for ATL;

- Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 2 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, hepatic and renal function

Exclusion Criteria:

- Smoldering subtype of ATL;

- Lymphomatous or acute subtype subject with > 2 prior systemic therapy regimens and who
has not achieved a response (CR or PR) or maintained stable disease for at least 12
weeks on last immediate prior therapy;

- History of allogeneic transplant;

- Autologous hematopoietic stem cell transplant within 90 days of study entry;

- Untreated human immunodeficiency virus (HIV)

- Has known hepatitis C. Patients who are hepatitis C antibody positive but are
hepatitis C quantitative PCR negative may be enrolled;

- Has hepatitis B based on PCR testing for hepatitis B virus DNA. Patients who are
hepatitis B core antibody positive but PCR negative may be enrolled if placed on
appropriate anti-hepatitis B virus prophylaxis prior to commencing treatment with
KW-0761. Patients who are hepatitis B core antibody positive based on prior
vaccination need not receive prophylaxis;

- Have had a malignancy in the past two years except non-melanoma skin cancers, melanoma
in situ, localized cancer of the prostate with current PSA < 0.1 µg/mL, treated
thyroid cancer or cervical carcinoma in situ or ductal/lobular carcinoma in situ of
the breast who is currently without evidence of disease;

- Clinical evidence of central nervous system (CNS) involvement or metastasis. In
subjects suspected of having CNS disease, an MRI of the brain and/or lumbar puncture
should be done to confirm;

- Psychiatric illness, disability or social situation that would compromise the
subject's safety or ability to provide consent, or limit compliance with study
requirements;

- Significant uncontrolled intercurrent illness

- Experienced allergic reactions to monoclonal antibodies or other therapeutic proteins;

- Known active autoimmune diseases will be excluded (For example; Grave's disease;
systemic lupus erythematosus; rheumatoid arthritis; Crohn's disease);

- Is pregnant (confirmed by beta human chorionic gonadotrophin [β-HCG]) or lactating.

- Prior treatment with KW-0761;

- Initiation of treatment with systemic corticosteroids while on study is only permitted
for acute and brief complications of underlying disease (e.g., hypercalcemia) or for
treatment related side effects (e.g., including pre-medication for infusion reaction,
nausea and vomiting). Subjects on systemic corticosteroids prior to enrollment must be
off for 7 days before initiation of study treatment, unless specifically indicated for
the treatment of hypercalcemia. (subjects may receive inhalation corticosteroids and
replacement doses of systemic corticosteroids as needed);

- Initiation of treatment with topical corticosteroids while on study is not permitted
except to treat an acute rash. Subjects on a stable dose of medium or low potency
topical corticosteroids for at least 4 weeks prior to Pre-treatment Visit may continue
use at the same dose, although the investigator should attempt to taper the use to
lowest dose tolerable;

- Have had interferon-α and/or zidovudine within 1 week, or anti-neoplastic
chemotherapy, radiation, immunotherapy, or investigational medications within 2 weeks
of first study treatment;

- Subjects on any immunomodulatory drug. Subjects on any immunomodulatory drug within 4
weeks of their first dose of KW-0761 are also excluded.