immunotoxin therapy in treating patients with hairy cell leukemia

Conditions: Leukemia

Summary: rationale: an immunotoxin can locate cancer cells and kill them without harming normal cells. this may be an effective treatment for hairy cell leukemia. purpose: phase i trial to study the effectiveness of bl22 immunotoxin in treating patients who have refractory or recurrent hairy cell leukemia.

objectives: * assess the toxicity and therapeutic efficacy of recombinant bl22 immunotoxin in patients with refractory or recurrent cd22+ hairy cell leukemia. * define the pharmacokinetics of this drug, including the terminal elimination serum half-life area under the curve and volume of distribution, in these patients. * evaluate the immunogenicity of this drug in these patients. * determine the effect of this drug on various components of the circulating cellular immune system in these patients. outline: this is a dose-escalation study. patients receive recombinant bl22 immunotoxin iv over 30 minutes on days 1, 3, and 5. treatment repeats at least every 42 days for up to 4 courses in the absence of disease progression and sufficient neutralizing antibodies. cohorts of 3-6 patients receive escalating doses of recombinant bl22 immunotoxin until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose at which no more than 1 of 6 patients experiences dose-limiting toxicity. projected accrual: a maximum of 46 patients will be accrued for this study within 3 years.

Eligibility criteria:
disease characteristics: * histologically confirmed refractory or recurrent hairy cell leukemia * relapsed after less than 2 years of complete remission after purine analog therapy * must have at least one of the following indications for therapy: * progressive or massive splenomegaly * cytopenia defined by the following: * absolute neutrophil count less than 1,000/mm\^3 or * platelet count less than 100,000/mm\^3 or * hemoglobin less than 12 g/dl * more than 20,000 hairy cells/mm\^3 * symptomatic adenopathy * constitutional symptoms including tumor-related fever or bone pain * evidence of cd22 positivity by 1 of the following: * more than 15% of malignant cells from a site must react with anti-cd22 by immunohistochemistry * more than 30% of malignant cells from a site cd22+ by fluorescent-activated cell sorter * more than 400 cd22 sites/cell (average) on malignant cells as assessed by radiolabeled anti-cd22 binding * no cns disease requiring treatment * no patients whose serum neutralizes bl22 immunotoxin in tissue culture, due to either antitoxin or antimouse-igg antibodies * no patients whose serum neutralizes more than 75% of the activity of 1 microgram/ml of bl22 immunotoxin patient characteristics: age: * 18 and over performance status: * karnofsky 60-100% life expectancy: * more than 6 months hematopoietic: * see disease characteristics * pancytopenia due to disease allowed hepatic: * alt and ast less than 2.5 times upper limit of normal (uln) * bilirubin less than 1.5 times uln renal: * creatinine no greater than 2.0 mg/dl pulmonary: * fev1 at least 60% of predicted * dlco at least 55% of predicted other: * hiv negative * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception prior concurrent therapy: biologic therapy: * prior bone marrow transplantation allowed * at least 3 weeks since prior interferon for the malignancy * more than 3 months since prior monoclonal antibody therapy (e.g., rituximab) chemotherapy: * see disease characteristics * at least 3 weeks since prior cytotoxic chemotherapy for the malignancy endocrine therapy: * not specified radiotherapy: * at least 3 weeks since prior whole body electron beam radiotherapy for the malignancy * radiotherapy within the past 3 weeks allowed provided less than 10% of total bone marrow was treated and patient has measurable disease outside the radiation port surgery: * not specified other: * at least 3 weeks since prior retinoids for the malignancy * at least 3 weeks since any other prior systemic therapy for the malignancy * no concurrent therapeutic warfarin

Keywords: refractory hairy cell leukemia