Safety Study to Evaluate Monoclonal Antibody KW-0761 in Subjects With Peripheral T-cell Lymphoma

Inclusion Criteria:

1. histologically/cytologically confirmed diagnosis of PTCL including CTCL (including MF and SS) but excluding ATLL.
2. failed at least one prior systemic therapy for PTCL or CTCL.
3. ECOG PS of \<=2 at study entry.
4. \>=18 years of age.
5. completed any prior therapy at least four weeks prior to entry; however, patients with rapidly progressive malignant disease may be enrolled prior to this period after discussion with the medical monitor.
6. resolution of all clinically significant toxic effects of prior cancer therapy to grade ≤1 by the NCI-CTCAE, v.3.0 excluding the specifications required in 7 and 8 below.
7. adequate hematological function: absolute neutrophil count\>=1,500 cells/uL and platelets \>=100,000 cells/uL except in patients with known bone marrow involvement where absolute neutrophil count must be \>=1,000 cells/uL and platelets \>=75,000 cells/uL.
8. adequate hepatic function: bilirubin ≤ 1.5 times the specific institutional ULN; aspartate transaminase and alanine transaminase each ≤ 2.5 x ULN or ≤ 5.0 x ULN in the presence of known hepatic malignancy.
9. serum creatinine ≤1.5 x ULN or a calculated creatinine clearance \>60 mL/min.
10. CTCL subjects previously treated with zanolimumab are eligible provided their CD4+ cell counts have recovered to pre-treatment levels.
11. Subjects with MF and a history of staphylococcus colonization are eligible provided they continue to receive stable doses of prophylactic antibiotics.
12. provided signed informed consent.
13. WOCBP must have a negative pregnancy test within 7 days of receiving study medication.
14. WOCBP must agree to use effective contraception
15. Male subjects must be willing to use an appropriate method of contraception (e.g., condoms) or abstain from sexual intercourse and inform any sexual partners that they must also use a reliable method of contraception during the study.

Exclusion Criteria:

1. has a 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 \>160 mm Hg, diastolic BP \>100 mmHg, found on two consecutive measurements separated by a 1-week period) despite two anti-hypertensive medications; clinically significant cardiac arrhythmia; or uncontrolled diabetes.
2. has known or tests positive for human immunodeficiency virus (HIV), human T-cell leukemia virus (HTLV-1), hepatitis B or hepatitis C.
3. has evidence of central nervous system (CNS) metastasis.
4. has received monoclonal antibodies within 6 weeks of study entry.
5. is pregnant (confirmed by beta human chorionic gonadotrophin \[β-HCG\]) or lactating.
6. Subjects on any immunomodulatory drug, (other than low dose corticosteroids equivalent to a daily dose of 10 mg of prednisone). Subjects on any immunomodulatory drug within 4 weeks of their first dose of KW-0761 are also excluded.
7. has a psychiatric illness, disability or social situation that would compromise the subject's safety or ability to provide consent, or limit his or her compliance with study requirements.
8. has experienced allergic reactions to monoclonal antibodies or other therapeutic proteins.
9. Subjects with active herpes simplex or herpes zoster. Subjects with a history of herpes zoster who have had an outbreak within the last year will also be excluded. Subjects on prophylaxis for herpes who started taking medication at least 30 days prior to study entry, should continue to take the prescribed medication for the duration of the study.
10. Subjects with known autoimmune diseases. Subjects with Hashimoto's thyroiditis controlled with medication are eligible for enrollment.