y 90 ibritumomab tiuxetan &rituximab relapsed or refractory diffuse large b-cell non-hodgkin's lymphoma

Conditions: Lymphoma

Summary: rationale: monoclonal antibodies, such as yttrium y 90 ibritumomab tiuxetan and rituximab, can locate cancer cells and either kill them or deliver radioactive cancer-killing substances to them without harming normal cells. combining yttrium y 90 ibritumomab tiuxetan with rituximab may kill more cancer cells. purpose: phase ii trial to study the effectiveness of combining yttrium y 90 ibritumomab tiuxetan with rituximab in treating patients who have relapsed or refractory diffuse large b-cell non-hodgkin's lymphoma.

objectives: * determine the best overall response in patients with relapsed or refractory diffuse large b-cell non-hodgkin's lymphoma treated with yttrium y 90 ibritumomab tiuxetan and rituximab. * determine the event-free survival of patients treated with this regimen. * determine the toxicity of this regimen in these patients. outline: this is an open-label, multicenter study. * radioimmunotherapy: patients receive indium in 111 ibritumomab tiuxetan iv over 10 minutes on day 1 (for imaging only); yttrium y 90 ibritumomab tiuxetan iv over 10 minutes on day 8; and rituximab iv over 3-4 hours on days 1, 8, 15, 22, 29, and 36. * cns ( central nervous system)prophylaxis: patients receive cns prophylaxis comprising intrathecal (it) methotrexate or it cytarabine on days 15, 22, 29, and 36 or it cytarabine (liposomal) on days 15 and 29. * maintenance rituximab: patients are assessed for response at week 14. beginning at month 6, patients with stable or responding disease receive maintenance therapy comprising rituximab iv over 3-4 hours once weekly for 4 weeks. maintenance therapy repeats every 6 months for 2 years (total of 4 courses) in the absence of disease progression or unacceptable toxicity. patients are followed every 3 months for 2 years and then every 6 months for 2 years. projected accrual: a total of 40 patients will be accrued for this study within 2 years.

Eligibility criteria:
disease characteristics: * histologically confirmed diffuse large b-cell non-hodgkin's lymphoma, including any of the following: * b-cell diffuse large cell variant * immunoblastic * mediastinal (thymic) large cell * t-cell/histiocyte-rich * anaplastic large b-cell * intravascular large b-cell * lymphomatoid granulomatosis * relapsed or refractory disease after at least 1 prior chemotherapy regimen and requires further treatment * relapsed disease, defined as the following: * appearance of any new lesion or increase of at least 50% in the size of a previously involved site * 50% increase in greatest diameter of any previously identified node greater than 1 cm in the short axis or in the sum of the perpendicular diameter (spd) of more than 1 node * progressive disease, defined as the following: * 50% increase from nadir in the spd of any previously identified abnormal node * appearance of any new lesion during or at the end of therapy * cd20-positive disease by immunohistochemistry * bidimensionally measurable disease * at least 1 lesion at least 2.0 cm by ct scan * less than 25% bone marrow involvement by lymphoma * no transformed lymphoma from indolent to aggressive * no hiv- or aids-related lymphoma * no hypocellular bone marrow * no marked reduction in bone marrow precursors of 1 or more cell lines (e.g., granulocytic, megakaryocytic, or erythroid) * no cns lymphoma * ineligible for myeloablative therapy or refused transplantation * ineligible for any other open yttrium y 90 ibritumomab tiuxetan investigational protocols patient characteristics: age * 18 and over performance status * who 0-2 life expectancy * at least 3 months hematopoietic * absolute neutrophil count at least 1,500/mm\^3 * lymphocyte count no greater than 5,000/mm\^3 (for patients with small lymphocytic lymphoma) * platelet count at least 100,000/mm\^3 hepatic * bilirubin no greater than 2.0 mg/dl renal * creatinine no greater than 2.0 mg/dl other * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception during and for 1 year after study participation * no concurrent serious nonmalignant disease or infection that would preclude study participation * no human antimurine antibody reactivity prior concurrent therapy: biologic therapy * see disease characteristics * no prior autologous bone marrow transplantation * no prior peripheral blood stem cell rescue * no prior failed stem cell collection * prior rituximab within the past 90 days allowed provided patient has fludeoxyglucose-avid disease that is also indium in 111 ibritumomab tiuxetan-avid disease in at least 1 lesion * more than 2 weeks since prior filgrastim (g-csf) or sargramostim (gm-csf) chemotherapy * see disease characteristics endocrine therapy * not specified radiotherapy * no prior radioimmunotherapy * no prior external beam radiotherapy (involved field or regional) to more than 25% of active bone marrow surgery * more than 4 weeks since prior major surgery (except diagnostic surgery) other * recovered from all prior therapy * more than 4 weeks since prior therapy for lymphoma * more than 8 weeks since prior phase ii investigational drugs * no other concurrent antineoplastic therapy

Keywords: recurrent adult diffuse large cell lymphoma recurrent adult immunoblastic large cell lymphoma anaplastic large cell lymphoma