• Duration of response at 1 month after study completion [ Designated as safety issue: No ]
  

OBJECTIVES:

• Determine the toxicity of saturating doses of daclizumab directed toward interleukin-2 receptor (IL-2R) in patients with Tac-expressing HTLV-I-associated adult T-cell leukemia/lymphoma.
• Determine the dose of daclizumab required to saturate IL-2R in patients with different serum concentrations of soluble IL-2R.
• Define the pharmacokinetics of this regimen in these patients.
• Determine the efficacy (response rate, duration of response, and overall survival) of saturating doses of daclizumab in these patients.

OUTLINE:

• Phase I (closed to accrual 6/11/01):

This is a dose-escalation study.

The first cohort of 3 patients receives daclizumab IV over 30 minutes on days 1 and 2. The subsequent 3 cohorts of 3-6 patients receive daclizumab IV over 90 minutes on day 1. In the absence of disease progression or unacceptable toxicity, patients receive up to 5 additional courses of daclizumab at the dose level of the cohort being studied at weeks 2, 5, 8, 11, and 14.

Cohorts of 3-6 patients receive escalating doses of daclizumab until the saturating dose is achieved or until the maximum tolerated dose (MTD) is determined. The saturating dose is defined as the dose at which 6 of 6 patients have adult T-cell leukemia cells saturated at 6-72 hours after initial daclizumab administration and then at 2 and 5 weeks prior to subsequent daclizumab administration. The MTD is defined as the dose preceding that at which 1 of 3 or 2 of 6 patients experience dose-limiting toxicity.

• Phase II:

Patients receive daclizumab at the saturating dose from phase I of the study. If a saturating dose was not achieved by the fourth cohort during phase I, then the fourth cohort dose level is used for phase II of the study.

Patients who achieve and maintain a partial response to treatment after 6 courses in the absence of dose-limiting toxicity may continue to receive daclizumab for a total of 24 months.

Patients are followed every 2 months for 1 year.

PROJECTED ACCRUAL: A total of 53 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically proven Tac-expressing adult T-cell leukemia/lymphoma (ATL), including any of the folllowing stages:

  • Lymphomatous (closed to accrual as of 10/3/05)
  • Acute (closed to accrual as of 10/3/05)
  • Chronic

  • Smoldering, meeting the following criteria:

    • Normal lymphocyte count (less than 4,000/mm^3)
    • At least 5% abnormal lymphocytes by morphologic examination on peripheral blood smear or FACS analysis (if less than 5% abnormal lymphocytes, then must have at least 1 histologically proven skin ATL lesion)
    • No hypercalcemia
    • Lactate dehydrogenase no greater than 1.5 times upper limit of normal (ULN)
    • No lymphadenopathy
    • No involvement of extranodal organs except skin or lung
    • No malignant pleural effusion or ascites
• HTLV-I antibody positive
• Reactivity of at least 5% of peripheral blood, lymph node, pulmonary, or dermal malignant cells with daclizumab as determined by immunofluorescent staining OR soluble interleukin-2 receptor levels greater than 1,000 U/mL required
• Measurable disease, defined as greater than 5% abnormal (i.e., Tac-homogenous strongly expressing) peripheral blood mononuclear cells

• No symptomatic CNS disease due to ATL

  • Tac-expressing T-cells may be present in the CSF
• ATL with concurrent tropical spastic paraparesis allowed

PATIENT CHARACTERISTICS:

Age:

• 10 and over

Performance status:

• Karnofsky 70-100%

Life expectancy:

• More than 2 months

Hematopoietic:

• See Disease Characteristics
• Granulocyte count at least 500/mm^3
• Platelet count at least 25,000/mm^3

Hepatic:

• See Disease Characteristics
• SGOT and SGPT less than 5 times ULN*
• Bilirubin no greater than 2.9 mg/dL* NOTE: * Unless due to ATL

Renal:

• See Disease Characteristics
• Creatinine less than 3.0 mg/dL

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Prior monoclonal antibody (MOAB) therapy including daclizumab allowed if human antibody to humanized anti-Tac (HAHA) negative (i.e., HAHA must be less than 250 ng/mL)
• No other concurrent MOAB therapy
• No concurrent gammaglobulins
• No concurrent interferons or other biologic response modifiers

Chemotherapy:

• More than 3 weeks since prior chemotherapy for ATL
• No concurrent chemotherapy

Endocrine therapy:

• Concurrent corticosteroids allowed

Radiotherapy:

• Not specified

Surgery:

• Not specified

Other:

• No other concurrent investigational anticancer drugs
• No concurrent FDA-approved anticancer agents
• Concurrent antibiotics allowed for infections, including Pneumocystis carinii pneumonia
• No concurrent zidovudine
• No concurrent drugs that affect lymphocytes except corticosteroids