A Phase I/II Study of the Efficacy and Toxicity of Humanized Anti-Tac (Zenapax(Trademark)) in the Therapy of Tac-Expressing Adult T-Cell Leukemia

Inclusion Criteria

- ELIGIBILITY CRITERIA:

- Population Base.

- Patients diagnosed with smoldering or chronic human T-lymphotropic virus type 1
(HTLV-I)- associated adult T-cell leukemia.

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.

- At least 5 percent of each patient's peripheral blood, lymph node, pulmonary or
dermal malignant cells must react with the anti-Tac mAb as determined by
immunofluorescent staining or, alternatively, the serum-soluble interleukin 2 (IL-2)
receptor levels must be greater than 1,000 units/ml (normal geometric mean, 235; with
a 95% confidence interval of 112 to 502 units/mL).

- Smoldering or chronic stage Tac-expressing adult T-cell leukemia defined by the
Shimomyama Criteria (37) are eligible.

- To be diagnosed as smoldering Adult T-cell Leukemia (ATL), the patient must have a
normal lymphocyte count (less than 4 times 10^3/mm^3), less than or equal to 5
percent abnormal lymphocytes on morphologic examination of the peripheral blood smear
or on fluorescence activated cell sorting (FACS) analysis (cells with a homogenous
staining pattern and a greater than 1 log increase in the magnitude of fluorescence
emission of the anti-Tac peak over background expression),

- no hypercalcemia,

- lactate dehydrogenase less than or equal to 1.5 times the upper limit of normal,

- no lymphadenopathy,

- no involvement of extra nodal organs except skin or lung and no malignant pleural
effusion or ascites.

- If the abnormal lymphocyte count is less than 5 percent, the patient must have at
least one histologically proven skin ATL lesion to be diagnosed as smoldering ATL.

- Patients with >5% of circulating lymphocytes that are abnormal are considered to have
measurable disease.

- The patient must have a granulocyte count of at least 500/mm^3 and a platelet count
of 25,000/mm^3.

- Patients must have a creatinine of less than 3.0 mg/dl.

- Patients must have a Karnofsky performance score of greater than 60 percent.

- ATL patients without, as well as those with, previous chemotherapy will be eligible
for inclusion in the study.

- Patients with previous therapy with a monoclonal antibody including anti-Tac will be
eligible for the study provided that they do not have a positive HAHA (human antibody
to humanized anti-Tac) value (i.e., such patients must have a value greater than 250
ng/ml).

- Omission of cytotoxic chemotherapy for ATL for 3 weeks prior to entry into the trial
is required.

- However, patients receiving corticosteroids will not be excluded.

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

- Eligible patients must be greater than or equal to 10 years old.

- There is no upper age limit.

- Patients over the age of 18 years must be able to understand and sign an Informed
Consent form.

- Eligible minors greater than or equal to 10 years old must give assent to participate
in this study.

EXCLUSION CRITERIA:

- Patients with symptomatic central nervous system disease that is due to the adult
T-cell leukemia will be excluded.

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

- Furthermore, Tac-expressing T cells may be present in the cerebrospinal fluid (CSF)
as long as the patient does not have symptomatic central nervous system (CNS)
disease.

- Pregnant and/or nursing patients are not eligible for the study.

- Human immunodeficiency virus (HIV) positive patients are excluded from the study.

- Patients with serum glutamic oxaloacetic transaminase (SGOT) or serum glutamic
pyruvic transaminase (SGPT) values 5.0-fold greater than the upper limit of normal or
bilirubin greater than 2.9 mg/dl will be excluded.

- 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.

- Acute or Lymphoma stage HTLV-1 associated adult T cell leukemia.