RATIONALE: Monoclonal antibodies such as epratuzumab can locate tumor cells and either kill
them or deliver tumor-killing substances to them without harming normal cells.
PURPOSE: Randomized phase II trial to study the effectiveness of epratuzumab in treating
patients who have non-Hodgkin's lymphoma.
- Determine the response rate of patients with diffuse large B-cell non-Hodgkin's
lymphoma treated with epratuzumab.
- Determine the toxicity of this drug in these patients.
OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 3
- Arm I: Patients receive low-dose epratuzumab IV over 1 hour once weekly for 4 weeks.
- Arm II: Patients receive low-dose epratuzumab IV over 1 hour once weekly for 8 weeks.
- Arm III: Patients receive high-dose epratuzumab IV over 1 hour once weekly for 4 weeks.
Patients are followed every 3 months for 2 years and then every 6 months thereafter.
PROJECTED ACCRUAL: A total of 150 patients (50 per treatment arm) will be accrued for this
- Histologically confirmed diffuse large B-cell non-Hodgkin's lymphoma (NHL)
- Relapsed or refractory after at least 1 regimen of standard therapy
- Prior therapy may include high-dose chemotherapy with autologous stem cell
transplantation (ASCT) or immunotherapy
- Bidimensionally measurable disease
- At least 1 lesion at least 1.5 cm by CT scan
- No primary or secondary CNS lymphoma
- No HIV-related lymphoma
- No known or suspected transformed lymphoma (prior or concurrent)
- No bulky disease (i.e., any single mass greater than 10.0 cm)
- No pleural effusion with positive cytology for lymphoma
- Most recent pathology specimen available for collection
- No rapid disease progression or symptoms that indicate disease progression requiring
rapid intervention within the past 2 weeks (e.g., severe shortness of breath, severe
pain, or gastrointestinal or genitourinary obstruction)
- 18 and over
- ECOG 0-2
- At least 4 months
- Absolute neutrophil count at least 1,000/mm3
- Platelet count at least 50,000/mm3 (transfusion independent)
- Hemoglobin at least 9.0 g/dL
- Bilirubin no greater than 2 times upper limit of normal (ULN)
- AST and ALT less than 5 times ULN
- Hepatitis B surface antigen negative
- Hepatitis C negative
- Creatinine no greater than 2 times ULN
- HIV negative
- No other primary malignancy within the past 3 years except squamous cell or basal
cell skin cancer, carcinoma in situ of the cervix, or stage I prostate cancer
- No other serious nonmalignant condition that would preclude study
- No serious infection
- No known human antichimeric antibodies or human antihuman antibody positivity
- No type 1 hypersensitivity or anaphylactic reactions to murine proteins
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for at least 6 months
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- At least 4 weeks since prior immunotherapy (unless clearly progressing)
- At least 12 weeks since prior ASCT
- See Disease Characteristics
- At least 4 weeks since prior chemotherapy (unless clearly progressing)
- Not specified
- No prior radioimmunotherapy
- At least 4 weeks since prior major surgery (unless patient has fully recovered)
- At least 30 days since prior enrollment in clinical trials involving investigational
devices or drugs
- No concurrent enrollment in other clinical trials involving investigational devices
- No concurrent investigational agents for disease other than NHL