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

Multi-Center, Open-Label, Randomized Study of Anti-CCR4 Monoclonal Antibody KW-0761 or Investigator's Choice in Subjects With Previously Treated Adult T-cell Leukemia-Lymphoma (ATL)

The purpose of this study is to estimate the overall response rate of subjects with relapsed or refractory 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.