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

Phase 2
18 Years
Open (Enrolling)
Leukemia, Adult T-Cell

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Trial Information

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
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


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.


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.

Inclusion Criteria


Patients must have serum antibodies directed to human T-lymphotropic virus type 1

All patients must have a histologically confirmed diagnosis of adult T-cell
leukemia/lymphoma and more than 10% of the malignant cells must express cluster of
differentiation 25 (CD25).

All stages of Tac-expressing adult T cell leukemia except smoldering are eligible:
patients with chronic, lymphomatous or acute adult T-cell leukemia (ATL) are eligible.
(See appendix 2 for characteristics of patients with the various stages of ATL)

Patients must have measurable disease. All patients with greater than 10% abnormal (i.e.
TAC homogenous strongly expressing) peripheral blood mononuclear cells (PBMC) in the
peripheral blood will be deemed to have measurable disease.

The patient must have a granulocyte count of at least 1000/mm^3 and a platelet count of
greater than or equal to 50,000/mm^3.

Patients must have a creatinine of less than 2.0 mg/dl.

Omission of cytotoxic chemotherapy for ATL for 3 weeks prior to entry into the trial is
required. However, patients receiving corticosteroids will be eligible.

Patients must have a life expectancy of greater than 2 months.

Eligible patients must be greater than or equal to 18 years old. There is no upper age

Patients must have serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic
pyruvic transaminase (SGPT) value less than or equal to 2.5 times the upper limit of
normal and bilirubin less than or equal to 3.0/dl. If a liver function test is judged to
be elevated due to the underlying ATL, this parameter will be considered an unevaluable
parameter for toxicity determinations.

Patients must have a serum albumin greater than or equal to 2.5 g/dl

Patients must be able to understand and sign an Informed Consent form.

All patients must use adequate contraception during participation in this trial and for
three months after completing therapy.


Patients with symptomatic leukemic meningitis will be excluded. However, patients that
have both ATL and another HTLV-I-associated disease, tropical spastic paraparesis (TSP),
will be included.

Pregnant and nursing patients are not eligible for the study.

Human immunodeficiency virus (HIV) positive patients are excluded from the study.
Denileukin diftitox may produce a different pattern of toxicities in immunocompromised

Patients with Smoldering ATL are excluded.

Patients with serious intercurrent illnesses, past history of a myocardial infarction
within 6 months or severe coronary artery disease

Patients who previously received Denileukin diftitox are ineligible.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Response Rate

Outcome Description:

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.

Outcome Time Frame:

up to 12 months

Safety Issue:


Principal Investigator

Thomas A Waldmann, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Institute (NCI)


United States: Federal Government

Study ID:




Start Date:

July 2005

Completion Date:

December 2012

Related Keywords:

  • Leukemia, Adult T-Cell
  • Denileukin Diftitox (Ontak)
  • Recombinant Immunotoxin
  • Human T-Cell Lymphotropic Virus (HTLV1)
  • CD25 Positive
  • IL-2R
  • ATL
  • Ontak
  • Adult T-Cell Leukemia
  • Lymphoproliferative Disorders
  • Leukemia
  • Leukemia, T-Cell
  • Leukemia-Lymphoma, Adult T-Cell



National Institutes of Health Clinical Center, 9000 Rockville Pike Bethesda, Maryland  20892