Phase II Study of the Efficacy and Toxicity of Ontak (Denileukin Diftitox) in the Therapy of Adult T-Cell Leukemia
Adult T-Cell Leukemia is a lymphoproliferative disorder characterized by the presence of
CD4/CD25 expressing T cells (IL-2R expressing) in the peripheral blood, in lymphoid and
Denileukin diftitox is a genetically engineered fusion protein combining the enzymatically
active domains of diphtheria toxin (DT) and the full length sequence of interleukin-2 (IL-2)
that targets IL-2 expressing malignancies.
Denileukin diftitox interacts with the IL-2 R on the cell surface, is internalized via
endocytosis, and inhibits cellular protein synthesis resulting in cell death within hours to
Determine the clinical response to Denileukin diftitox (Ontak) of patients with adult T-cell
Define the safety of Denileukin diftitox in patients who have ATL.
Patients with chronic, lymphomatous and acute forms of ATL.
Patients must be human T-cell lymphotropic virus type I (HTLV1) positive.
Patients will be treated with 9mcg/kg/d of Denileukin diftitox for five days, on an every
two week schedule.
Tumor response will be evaluated after two cycles of treatment. Stable or responding
patients will continue treatment with evaluations every four cycles of treatment. Patients
will be treated for two cycles beyond a complete remission.
The trial uses an optimal 2 stage design targeting for a true response proportion greater
than 30%. Nine patients will be treated initially with expansion to 29 patients if a
response is seen in one of the initial nine patients treated. If no response is seen at the
9 mcg/kg/d dose an additional 9 patients will be treated at a dose of 18 mcg/kg/d with
expansion to 29 patients at this dose level if a response is seen. A stopping rule for
excessive toxicity will be incorporated.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Response rate is based on the number of patients who achieve either a complete response (CR) or partial response (PR) to therapy. Complete response is complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease related symptoms if present before therapy and normalization of those biochemical abnormalities (for example LDH) definitely assignable to the lymphoma. Partial response is reduction by >=50% of leukemia cell count or >=50% reduction is the size of all measurable lesions, and no increase in size of any measurable or evaluable lesion or appearance of new lesion.
up to 12 months
Thomas A Waldmann, M.D.
National Cancer Institute (NCI)
United States: Federal Government
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