A Phase II Study To Evaluate The Safety And Efficacy Of Zevalin (IND # BB IND 4850) Therapeutic Regimen In Patients With Transformed CD20 + B-Cell Non-Hodgkin's Lymphoma

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed transformed CD20+ B-cell non-Hodgkin's lymphoma (NHL)

- Transformation defined as:

- Progression to a more aggressive diffuse lymphoma, excluding conversion to
a more aggressive grade of follicular lymphoma (e.g., WHO/REAL follicular
center, large, grade III NHL)

- Initial large cell follicular lymphoma must progress to a diffuse large cell
lymphoma

- De novo transformed NHL ineligible

- Requiring treatment as determined by any of the following characteristics:

- An increase in overall tumor size

- Presence of B symptoms

- Presence of masses that are causing ongoing clinical symptomatology

- Must have less than 25% bone marrow involvement with lymphoma

- Must have received and either relapsed or failed to respond to prior therapy for
initial low grade or follicular NHL

- Must have bidimensionally measurable disease defined as:

- Greater than 2 cm OR 1.5 cm if 0.5 cm slices are used during spiral CT scan

- Nonmeasurable disease includes any of the following:

- Bone lesions

- Leptomeningeal disease

- Ascites

- Pleural or pericardial effusion

- Inflammatory breast disease

- Lymphangitis cutis/pulmonis

- Abdominal masses that are not confirmed and followed by imaging techniques

- Cystic lesions

- Lesions that are situated in a previously irradiated area

- No expected impairment in bone marrrow reserve meeting any of the following criteria:

- Platelet count less than 150,000/mm^3

- Hypocellular bone marrow (less than 15% cellularity)

- Marked reduction in bone marrow precursors of one or more cell lines (e.g.,
granulocytic, megakaryocytic, or erythroid)

- History of failed stem cell collection

- Patients with peritoneal invasion and/or ascites with positive cytology for lymphoma
OR pleural invasion and/or effusion with positive cytology for lymphoma are eligible
only if their effusion or ascites can be tapped dry

- No significant remaining malignant effusion or ascites at the time of study drug
administration

- No known meningeal lymphoma or known parenchymal CNS lymphoma NOTE: A new
classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The
terminology of "indolent" or "aggressive" lymphoma will replace the former
terminology of "low", "intermediate", or "high" grade lymphoma. However, this
protocol uses the former terminology.

PATIENT CHARACTERISTICS:

Age

- 18 and over

Performance status

- 0-2

Life expectancy

- Not specified

Hematopoietic

- See Disease Characteristics

- Absolute neutrophil count at least 1,500/mm^3

- Lymphocyte count no greater than 5,000/mm^3

- Platelet count at least 150,000/mm^3

Hepatic

- Bilirubin no greater than 2.0 mg/dL

Renal

- Creatinine no greater than 2.0 mg/dL

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 1 year after study
treatment

- HIV negative

- No other malignancy except nonmelanoma skin cancer unless patient has completed
therapy and is considered to be at less than 30% risk of relapse

- No human anti-mouse antibody (HAMA) reactivity (patients with prior exposure to
murine antibodies)

PRIOR CONCURRENT THERAPY:

Biologic therapy

- See Radiotherapy

- At least 3 weeks since prior anticancer immunotherapy (6 weeks for rituximab) and
recovered

- More than 2 weeks since prior filgrastim (G-CSF) or sargramostim (GM-CSF)

- No prior myeloablative therapy with bone marrow transplantation or peripheral blood
stem cell rescue

Chemotherapy

- See Biologic therapy

- At least 3 weeks since prior anticancer chemotherapy (6 weeks for nitrosourea or
mitomycin) and recovered

Endocrine therapy

- No concurrent systemic corticosteroids with either of the following dose schedules:

- No greater than 50 mg of prednisone as a single dose (or equivalent)

- No greater than 50 mg of prednisone per dose (or equivalent) for more than 6
doses

Radiotherapy

- See Disease Characteristics

- At least 3 weeks since prior anticancer radiotherapy and recovered

- No prior radioimmunotherapy, including yttrium Y 90 ibritumomab tiuxetan

- No prior external beam radiotherapy to more than 25% of active bone marrow (involved
field or regional)

Surgery

- At least 3 weeks since prior anticancer surgery and recovered

- More than 4 weeks since prior major surgery (other than diagnostic surgery)

Other

- At least 3 weeks since other prior anticancer therapy and recovered