denileukin diftitox in treating patients with fludarabine-refractory b-cell chronic lymphocytic leukemia

Conditions: Leukemia

Summary: 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

Keywords: b-cell chronic lymphocytic leukemia refractory chronic lymphocytic leukemia