Denileukin Diftitox in Treating Patients With Fludarabine-Refractory B-Cell Chronic Lymphocytic Leukemia

RATIONALE: Biological therapies, such as denileukin diftitox, may interfere with the growth of cancer cells and slow the growth of chronic lymphocytic leukemia.

PURPOSE: This phase II trial is studying how well denileukin diftitox works in treating patients with fludarabine-refractory B-cell chronic lymphocytic leukemia.

OBJECTIVES:

Primary

* Determine the complete and partial response rate in patients with fludarabine-refractory B-cell chronic lymphocytic leukemia treated with denileukin diftitox.

Secondary

* Determine the toxicity profile of this drug in these patients.
* Determine the response rate in patients (regardless of CD25 receptor density) treated with this drug.
* Determine the progression-free survival and overall survival of patients treated with this drug.

OUTLINE: This is a multicenter study.

Patients receive denileukin diftitox IV over 1 hour on days 1-5. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

Patients achieving a complete response after 8 courses proceed to follow-up. Patients achieving a partial response or stable disease after 8 courses may continue treatment at the discretion of the investigator.

Patients are followed every 3 months for 1 year and then annually until relapse.

PROJECTED ACCRUAL: A total of 12-44 patients will be accrued for this study within 1 year.

Eligibility 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