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.
- 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
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.
- 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 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.)
- 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
- 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 <
- Positive human anti-mouse antibodies (HAMA) serum values, defined as > 74 ng/mL at
- 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
- Erythropoietin (EPO) within a month of screening laboratory assessment
- Whole blood or platelet transfusion within 120 hours of screening laboratory
- 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.