A Phase II Study of ONTAK® (Denileukin Diftitox, DABIL-2) in Patients With Fludarabine-Refractory B-Cell Chronic Lymphocytic Leukemia

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Diagnosis of B-cell chronic lymphocytic leukemia (CLL) meeting the following criteria
at any time during the course of disease (e.g., at initial diagnosis or relapse):

- Absolute lymphocytosis > 5,000/mm^3

- Lymphocytes must appear mature with < 55% prolymphocytes

- More than 30% of all nucleated cells are lymphoid on bone marrow aspirate smear

- Lymphoid infiltrates compatible with bone marrow involvement by CLL on core bone
marrow biopsy

- Predominant B-cell monoclonal population of cells share the B-cell marker (CD19)
with the CD5 antigen in the absence of other pan-T-cell markers by lymphocyte
immunophenotyping

- High-risk disease OR intermediate-risk disease

- Patients in the intermediate-risk group must have evidence of active disease as
demonstrated by at least 1 of the following criteria:

- Massive or progressive splenomegaly and/or adenopathy

- Weight loss > 10% within the past 6 months

- Common toxicity grade 2-4 fatigue

- Fevers > 100.5°F OR night sweats for more than 2 weeks without evidence of
infection

- Progressive lymphocytosis with an increase of > 50% over a 2-month period
or an anticipated doubling time of < 6 months

- Failed at least 1 prior fludarabine regimen, as defined by 1 of the following
criteria:

- Refractory or intolerant to fludarabine

- Relapsed within 6 months after completion of fludarabine

- No CNS leukemia

- No mantle cell lymphoma in leukemic phase

PATIENT CHARACTERISTICS:

Age

- 18 and over

Performance status

- Zubrod 0-2

Life expectancy

- More than 2 months

Hematopoietic

- Absolute neutrophil count ≥ 1,000/mm^3

- Platelet count ≥ 50,000/mm^3

- Hemoglobin ≥ 8 g/dL (transfusion allowed)

Hepatic

- Albumin ≥ 3 g/dL

- AST and ALT ≤ 2.5 times upper limit of normal (ULN)

- Bilirubin ≤ 1.5 times ULN

- No hepatitis B or C infection

Renal

- Creatinine ≤ 1.5 mg/dL OR

- Creatinine clearance ≥ 40 mL/min

Cardiovascular

- LVEF ≥ 40%

Other

- No uncontrolled infection

- No other concurrent serious illness

- No HIV infection

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use two effective methods of contraception (one must be
non-hormonal) during and for at least 1 month after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

- Prior denileukin diftitox allowed

Chemotherapy

- See Disease Characteristics

Endocrine therapy

- No concurrent corticosteroids as anti-emetics

Radiotherapy

- No concurrent radiotherapy

Surgery

- Not specified

Other

- At least 28 days since prior anticancer therapy and recovered

- No other concurrent antineoplastic drugs