radiolabeled monoclonal antibody in treating patients with previously treated large cell lymphoma

Conditions: Lymphoma

Summary: rationale: radiolabeled monoclonal antibodies can locate tumor cells and deliver tumor-killing substances such as radioactive iodine to them without harming normal cells. purpose: phase i trial to study the effectiveness of radiolabeled monoclonal antibodies in treating patients who have large cell lymphoma that has been previously treated.

objectives: * determine the maximum tolerated dose of iodine i 131 monoclonal antibody lym-1 in patients with previously treated diffuse large cell lymphoma. * determine the safety of this drug in these patients. * determine the response of patients to this drug. outline: this is a dose-escalation, multicenter study. patients receive unlabeled monoclonal antibody lym-1 iv over 40 minutes followed 15-30 minutes later by iodine i 131 monoclonal antibody lym-1 iv over 2 minutes. cohorts of 3-6 patients receive escalating doses of iodine i 131 monoclonal antibody lym-1 until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. patients are followed weekly for 8 weeks and then every 3 months for 1 year. projected accrual: a total of 8-36 patients will be accrued for this study.

Eligibility criteria:
inclusion criteria * histologic diagnosis of b-cell diffuse large cell lymphoma (real classification system) confirmed by an independent central pathology reviewer. * the tumor's b-cell phenotype will be confirmed by positive l-26 (cd20). * previous treatment with 2 common combination chemotherapy regimens. patients previously treated with unlabeled monoclonal antibody therapy are eligible. * men or women at least 18 years of age. * karnofsky performance score (kps) estimated to be \> 60 at the time of the scheduled therapeutic dose of 131i-lym-1. * life expectancy estimated to be at least 3 months from the time of the therapeutic dose of 131i lym-1. * measurable disease demonstrable by physical examination or computerized tomography (ct). * ct scan evidence of at least one indicator lesion with at least one diameter that measures \> 2 cm. (the ct scan should be done within 2 weeks of the imaging study.) exclusion criteria * inability or unwillingness to comply with the following: * bone marrow biopsy * return for follow-up visits * remaining motionless for extended periods of time for imaging procedures * serial blood/urine sampling (for dosimetry patients only) * pregnancy (women of childbearing potential must be practicing an effective method of contraception.) * presence of a second malignancy except for basal cell skin carcinoma or carcinoma in-situ of the cervix * presence of active lymphomatous meningitis or other cns involvement with lymphoma. * hiv positive patients. * prior total body irradiation, or a course of prior radiation \> 3,000 cgy delivered to \> 20% of the central marrow or the lumbar vertebrae within 6 months of screening. * serum creatinine or total bilirubin \> 2 x the upper limit of normal. * aspartate aminotransferase (ast), alanine aminotransferase (alt) or alkaline phosphatase \> 3 x the upper limit of normal. * significant marrow lymphoma (defined as lymphoma cells constituting greater than 20% of the hematopoietic marrow elements from an iliac crest biopsy). a prior bone marrow biopsy is acceptable if it meets the following criteria: * if there is prior bone marrow involvement, the biopsy must be performed within 45 days of screening. * if there is no prior bone marrow involvement, the biopsy must be performed within 90 days of screening * wbc count \< 3,500/mm3, granulocyte count \< 1,500/mm3, or platelet count \< 125,000/mm3. * positive human anti-mouse antibodies (hama) serum values, defined as \> 74 ng/ml at screening. * patients who have not recovered from toxicities of most recent anti-lymphoma therapy. * treatment with: * colony stimulating factor g-csf or gm-csf within 120 hours of screening laboratory assessment. * erythropoietin (epo) within a month of screening laboratory assessment * whole blood or platelet transfusion within 120 hours of screening laboratory assessment * history or electrocardiographic (ecg) evidence of q-wave myocardial infarction within 6 months of screening or congestive heart failure (chf; nyha stage iii or iv). * known hypersensitivity to iodine or iodine-containing organic substances. * patients who require therapy with anticoagulants or antiplatelet drugs which cannot be discontinued during the study. * patients who are known to have antiplatelet antibodies.

Keywords: recurrent adult diffuse large cell lymphoma