Phase II Study of the Efficacy and Toxicity of Ontak(Registered Trademark) (Denileukin Diftitox) in the Therapy of Adult T-Cell Leukemia

Background:

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
other tissues.

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
days.

Objective:

Determine the clinical response to Denileukin diftitox (Ontak) of patients with ATL.

Define the safety of Denileukin diftitox in patients who have ATL.

Eligibility:

Patients with chronic, lymphomatous and acute forms of ATL.

Patients must be HTLV1 positive.

Design:

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.