Leukemia, Adult T-Cell Clinical Trial
Official title:
Phase II Study of the Efficacy and Toxicity of Ontak (Denileukin Diftitox) in the Therapy of Adult T-Cell Leukemia
Adult T-cell leukemia (ATL) is and aggressive characterized by the presence of cluster of
differentiation 4 (CD4)/cluster of differentiation 25 (CD25)-expressing T cells
(interleukin-2 [IL-2]R expressing) in the peripheral blood and in lymphoid and other tissues.
Denileukin diftitox (Ontak(Registered Trademark)) is a genetically engineered fusion protein
that targets IL-2-expressing malignancies. Denileukin diftitox interacts with the IL-2R on
the cell surface, is internalized via endocytosis, and inhibits cellular protein synthesis,
resulting in cell death within hours to days. The objectives of this study are to determine
the clinical response to Denileukin diftitox of patients with adult T-cell leukemia (ATL) and
the safety of Denileukin diftitox in those patients.
Eligible participants must be 18 years of age or older with chronic, lymphomatous and acute
forms of ATL, and must be infected with human T-cell lymphotropic virus type I (HTLV1).
Patients will be treated with 9 mcg/kg/d of Denileukin diftitox intravenously for 5 days
every 2 weeks. Tumor response will be evaluated after two cycles of treatment. Stable or
responding patients will continue treatment for a total of 12 months, with evaluations every
four cycles of treatment. Patients will be treated for two cycles beyond a complete
remission. The trial uses an optimal two-stage design targeting for a true response
proportion of more than 30 percent. Nine patients will be treated initially, with expansion
to 29 patients if a response is seen in 1 of the initial 9 patients treated. Treatment will
be discontinued if a patient experiences serious side effects.
A potential benefit is that a patient may undergo partial or complete remission. The research
may not directly benefit participants, but the results may aid in the treatment of others.
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 adult T-cell
leukemia (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 human T-cell lymphotropic virus type I (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.
;
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Terminated |
NCT01712659 -
Ruxolitinib for Adult T-Cell Leukemia
|
Phase 1/Phase 2 |