Daclizumab (Zenapax) Treatment for Tac-Expressing Adult T-Cell Leukemia

Background: Human T-lymphotropic virus type 1 (HTLV-1)-associated adult T cell leukemia/lymphoma (ATL) is an aggressive lymphoproliferative disorder. Chemotherapy has had limited impact on survival. The interleukin 2 receptor alpha (IL-2R alpha) (CD25) is over expressed on ATL cells and the smoldering and chronic stages of ATL are often interleukin 2 (IL-2) dependent. The monoclonal antibody daclizumab (Zenapax) inhibits interleukin 2 (IL-2) binding to its receptor. It is hypothesized that daclizumab may inhibit ATL growth. Objectives: To determine the toxicity and maximum tolerated dose (MTD) of humanized anti-Tac (daclizumab, Zenapax) in patients with ATL. To define the dose of Zenapax required to saturate IL-2R alpha in patients with ATL. To determine the clinical response to humanized (Hu) anti-Tac (Zenapax) of patients with Tac-expressing smoldering and chronic stage adult T cell leukemia. To determine the serum dieaway curve (pharmacokinetics) of infused humanized (Hu) - anti - Tac in patients who have ATL. Eligibility: Smoldering and chronic stage HTLV-1-associated adult T cell leukemia. At least 5 percent of malignant cells in the peripheral blood or lymph nodes must react with the anti-Tac (CD25) antibody. Age greater than or equal to 10-years-old. Patients must have measurable disease. Patients with and without prior treatment. Patients must have a granulocyte count of greater than or equal to 500/micro L, platelets greater than or equal to 25,000/micro L, and creatinine less than 3.0 gm/dL. Design: Phase I patients on cohorts 1-4 received the following: cohort 1: 2 mg/kg over 60 minutes intravenously on days 1 and 2; cohort 2: 4 mg/kg over 90 minutes intravenously on day 1, single dose; cohort 3: 6 mg/kg over 90 minutes intravenously on day 1, single dose; and cohort 4: 8 mg/kg over 90 minutes intravenously on day 1, single dose. Patients with smoldering or chronic stage ATL will be treated with intravenous daclizumab 8 mg/kg on day 0 and weeks 2, 5, 8, 11 and 14. Patients achieving a response will continue on treatment with daclizumab 8 mg/kg every 3 weeks for up to 24 months. Patients achieving a complete response (CR) will continue on treatment with daclizumab 8mg/kg every 3 weeks for up to 24 months. Patients achieving a partial response (PR) will be maintained on daclizumab 8 mg/kg administered every 3 weeks provided the PR is maintained and no serious adverse event or toxicity related to daclizumab therapy is observed.