monoclonal antibody therapy in treating patients with leukemia

Conditions: Lymphoma; Radiation Toxicity

Summary: rationale: monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. purpose: phase i/ii trial to study the effectiveness of radiolabeled monoclonal antibody plus pentetic acid calcium in patients with leukemia.

objectives: * determine the maximum tolerated dose of yttrium y 90 daclizumab (90y daclizumab) when combined with pentetic acid calcium in adults with tac-expressing t-cell leukemia. * determine the therapeutic efficacy and toxicity of this regimen in these patients. * monitor patients treated on this regimen for circulating infused antibody (free and labeled) and for the serum concentration of soluble interleukin-2 receptor. * evaluate, in a preliminary manner, the immunogenicity of daclizumab. * determine the effect of 90y daclizumab on various components of the circulating cellular immune system. * determine whether there is additional urinary excretion of yttrium y 90 when compared to that observed previously in patients treated without pentetic acid calcium. outline: this is a dose escalation study of yttrium y 90 daclizumab (90y daclizumab). patients receive 90y daclizumab iv over 2 hours on day 1 and a fixed dose of pentetic acid calcium iv over 5 hours for 3 days. treatment repeats every 6 weeks for a maximum of 9 courses in the absence of disease progression or circulating antibodies to humanized anti-tac. cohorts of 3-6 patients receive escalating doses of 90y daclizumab 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 toxicities. additional patients are treated at the mtd. patients are followed at 4-6 weeks. projected accrual: up to 15 patients will be accrued for the phase i portion of the study. a total of 30 patients will be accrued for the phase ii portion of the study.

Eligibility criteria:
disease characteristics: * histologically confirmed adult t-cell leukemia or lymphoma (atl) of any stage * tac expression of malignant cells confirmed by one of the following: * at least 10% of peripheral blood, lymph node, or dermal malignant cells reactive with anti-tac by immunofluorescent staining * soluble interleukin-2 receptor levels greater than 1,000 u/ml (normal geometric mean = 235; 95% confidence intervals = 112-502 u/ml) * measurable disease required * more than 10% (i.e., strongly tac-expressing) abnormal cells in peripheral blood considered measurable disease * all stages of tac-expressing adult t-cell leukemia are eligible * smoldering atl patients are eligible only if the symptoms and sites of involvement by atl are such that there is a medical indication to treat * smoldering atl, defined as: * lymphocyte count less than 4,000/mm\^3 * less than 5% abnormal lymphocytes on morphologic exam of peripheral blood * no hypercalcemia * lactate dehydrogenase no greater than 1.5 times normal * no lymphadenopathy * no involvement of extranodal organs except skin or lung * no malignant pleural effusion or ascites * no symptomatic cns disease due to atl * concurrent diagnosis of tropical spastic paraparesis allowed * no detectable levels (i.e., greater than 250 ng/ml) of antibody to study drug as assessed by elisa patient characteristics: age: * 18 and over performance status: * not specified life expectancy: * greater than 2 months hematopoietic: * absolute granulocyte count at least 1,000/mm\^3 * platelet count at least 75,000/mm\^3 hepatic: * bilirubin less than 2.0 mg/dl (unless directly due to atl) * ast/alt less than 2.5 times normal renal: * creatinine less than 1.5 mg/dl or * creatinine clearance greater than 35 ml/min cardiovascular: * no clinical cardiac failure pulmonary: * no symptomatic pulmonary dysfunction unless due to underlying malignancy other: * hiv negative * not pregnant or nursing * negative pregnancy test prior concurrent therapy: biologic therapy * not specified chemotherapy * at least 4 weeks since prior cytotoxic chemotherapy endocrine therapy * concurrent corticosteroids allowed radiotherapy * not specified surgery * not specified other * not specified

Keywords: stage i adult t-cell leukemia/lymphoma stage ii adult t-cell leukemia/lymphoma stage iii adult t-cell leukemia/lymphoma stage iv adult t-cell leukemia/lymphoma recurrent adult t-cell leukemia/lymphoma radiation toxicity