monoclonal antibody therapy in treating patients with chronic lymphocytic leukemia

Conditions: Leukemia

Summary: rationale: monoclonal antibodies can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. purpose: phase i trial to study the effectiveness of monoclonal antibody therapy in treating patients who have chronic lymphocytic leukemia.

objectives: * evaluate the toxicity of murine monoclonal antibody mik-beta-1 (moab mik-beta-1) in patients with t-cell large granular lymphocytic leukemia associated with granulocytopenia, anemia, or thrombocytopenia. * determine the clinical response in patients treated with this drug. * assess the effect of this drug on the number of circulating cd3+, cd8+ expressing granular lymphocytes and the number of polymorphonuclear leukocytes, red blood cells, and platelets in this patient population. * monitor patients for the time course of decline in circulating infused moab mik-beta-1 and for the production of human antibodies to iv infused murine moab mik-beta-1. outline: this is a dose-escalation study. patients receive monoclonal antibody mik-beta-1 (moab mik-beta-1) iv over 2 hours on days 1, 4, 7, and 10. patients achieving a complete response (cr) or partial response (pr) may receive 1 additional course beginning no sooner than 4 weeks after completion of the first course, in the absence of antibodies to moab mik-beta-1. treatment continues in the absence of disease progression, unacceptable toxicity, or severe allergic reaction. cohorts of 3-6 patients receive escalating doses of moab mik-beta-1 until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. patients are followed at 6-10 days and at 4-6 weeks after therapy. patients with a pr or cr may be followed every 6 months for 2 years or until relapse. all patients are followed for survival. projected accrual: a maximum of 25 patients will be accrued for this study.

Eligibility criteria:
disease characteristics: * histologically confirmed t-cell large granular lymphocytic (t-lgl) leukemia associated with clinically significant hematocytopenia demonstrated by one of the following values while off growth factor support: * absolute neutrophil count less than 1,000/mm\^3 * hemoglobin less than 8 g/dl * platelet count less than 50,000/mm\^3 * clinically evaluable disease with peripheral blood t-lgl leukemia cells expressing the cd3+, cd8+ phenotype detectable by facs * monoclonal t-cell population in peripheral blood (circulating mononuclear cells) demonstrated by tcr beta or gamma chain gene rearrangement patient characteristics: age: * 18 and over performance status: * karnofsky 50-100% life expectancy: * more than 2 months hematopoietic: * see disease characteristics * no active major bleeding episode within the past 4 weeks hepatic: * direct bilirubin less than 1.5 mg/dl renal: * creatinine less than 2.0 mg/dl other: * no concurrent serious active infection * patients with fever without apparent site of infection may begin study while on antibiotics as long as the following are true: * no pathogenic organism in culture * afebrile (maximum temperature less than 38°c) for at least 5 days * hiv negative * no other primary cancer other than basal cell skin cancer * not pregnant or nursing * negative pregnancy test prior concurrent therapy: biologic therapy: * at least 4 weeks since prior interferon * concurrent filgrastim (g-csf), sargramostim (gm-csf), interleukin-11, or similar sustained-release/long-acting product (e.g., pegylated g-csf) allowed if dose established at least 4 weeks prior to study participation * no concurrent interferon chemotherapy: * at least 4 weeks since prior chemotherapy * no concurrent chemotherapy endocrine therapy: * concurrent corticosteroids allowed if dose established at least 3 weeks prior to study participation radiotherapy: * not specified surgery: * not specified other: * at least 1 week since completion of prior antibiotic regimen for serious infectious episode * no other concurrent investigational drugs

Keywords: refractory chronic lymphocytic leukemia t-cell large granular lymphocyte leukemia