- 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 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.
- Histologically confirmed diffuse large B-cell non-Hodgkin's lymphoma, including any of the following:
- B-cell diffuse large cell variant
- Mediastinal (thymic) large cell
- 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
- 18 and over
- WHO 0-2
- At least 3 months
- 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
- Bilirubin no greater than 2.0 mg/dL
- Creatinine no greater than 2.0 mg/dL
- 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:
- 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)
- See Disease Characteristics
- Not specified
- No prior radioimmunotherapy
- No prior external beam radiotherapy (involved field or regional) to more than 25% of active bone marrow
- More than 4 weeks since prior major surgery (except diagnostic surgery)
- 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
|Maximum Eligible Age:||N/A|
|Minimum Eligible Age:||18 Years|