Lymphoma
Conditions
Keywords
recurrent adult diffuse large cell lymphoma
Brief 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.
Detailed description
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.
Interventions
RADIATIONiodine I 131 monoclonal antibody Lym-1
Sponsors
National Cancer Institute (NCI)
Case Comprehensive Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Countries
United States
Outcome results
None listed