Phase II Study of the Efficacy and Toxicity of Ontak(Registered Trademark) (Denileukin Diftitox) in the Therapy of Adult T-Cell Leukemia
Condition: Leukemia, Adult T-Cell
MeSH terms: Leukemia; Leukemia, T-Cell; Leukemia-Lymphoma, Adult T-Cell
Intervention: Denileukin diftitox (Ontak)
Intervention description: Patients will be treated with Denileukin Diftitox 9 mcg/kg/d intravenously for 5 days every 2 weeks.
Intervention MeSH terms: Denileukin diftitox
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 17.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Denileukin Diftitox (Ontak); Recombinant Immunotoxin; Human T-Cell Lymphotropic Virus (HTLV1); CD25 Positive; IL-2R; ATL; Ontak; Adult T-Cell Leukemia; Lymphoproliferative Disorders

Summary:

      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.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

        Patients must have serum antibodies directed to human T-lymphotropic virus type 1 (HTLV-I).

        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
        limit.

        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.

        EXCLUSION CRITERIA:

        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
        individuals.

        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.