A Phase I/II Study of the Efficacy and Toxicity of Humanized Anti-Tac (Zenapax(Trademark)) in the Therapy of Tac-Expressing Adult T-Cell Leukemia
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
It is hypothesized that daclizumab may inhibit ATL growth.
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.
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.
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.
Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Duration of Response
Duration of response was defined as the interval from the time response is first achieved to the time progression from the best response is detected. Responses are assessed by a modified World Health Organization (WHO) criteria. Partial response is a reduction of >=50% saturation in the circulating leukemic cell count; complete response is disappearance of all measurable and non-measurable disease lasting more than 1 month; stable disease is patients who did not meet the criteria; and progressive disease is a >=25% increase in leukemic cell count.
Thomas Waldmann, M.D.
National Cancer Institute, National Institutes of Health
United States: Federal Government
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