Protocol Number: 05-C-0185

Title:

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

Number:

05-C-0185

Summary:

Adult T-cell leukemia (ATL) is and aggressive characterized by the presence of CD4/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 deftitox of patients with ATL and the safety of Denileukin deftitox 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 difitox 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.

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria:

INCLUSION CRITERIA:

Patients must have serum antibodies directed to 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 CD25.

All stages of Tac-expressing adult T cell leukemia except smoldering are eligible: patients with chronic, lymphomatous or acute 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) 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 SGOT and 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.

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.

Special Instructions:

Currently Not Provided

Keywords:

Ontak

Recombinant Immunotoxin

Human T-Cell Lymphotropic Virus (HTLV1)

CD25 Positive

IL-2R

Recruitment Keyword(s):

Adult T-Cell Leukemia

ATL

Lymphoproliferative Disorders

Condition(s):

Leukemia, Adult T-Cell

Investigational Drug(s):

None

Investigational Device(s):

None

Intervention(s):

Drug: Denileukin diftitox (Ontak)

Supporting Site:

National Cancer Institute

Contact(s):

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office
Phone: 1-888-NCI-1937
Fax: Not Listed
Electronic Address: ncicssc@mail.nih.gov

Citation(s):

Broder S, Bunn PA Jr, Jaffe ES, Blattner W, Gallo RC, Wong-Staal F, Waldmann TA, DeVita VT Jr. NIH conference. T-cell lymphoproliferative syndrome associated with human T-cell leukemia/lymphoma virus. Ann Intern Med. 1984 Apr;100(4):543-57. Review.

Uchiyama T, Yodoi J, Sagawa K, Takatsuki K, Uchino H. Adult T-cell leukemia: clinical and hematologic features of 16 cases. Blood. 1977 Sep;50(3):481-92. No abstract available.

Poiesz BJ, Ruscetti FW, Gazdar AF, Bunn PA, Minna JD, Gallo RC. Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma. Proc Natl Acad Sci U S A. 1980 Dec;77(12):7415-9. No abstract available.

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
• Technical questions regarding the Clinical Center web site, please contact the Department of Clinical Research Informatics, CC.

Search The Studies | Help | Questions |
Clinical Center Home | NIH Home

National Institutes of Health Clinical Center Bethesda, Maryland 20892. Last update: 01/13/2009