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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Leukemia

Intervention / Treatment
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* Biological: denileukin diftitox


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: denileukin diftitox|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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B-cell chronic lymphocytic leukemia, refractory chronic lymphocytic leukemia