Rituximab, Yttrium Y 90 Ibritumomab Tiuxetan in Patients W/Relapsed Stage II, III, or IV Follicular NHL

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Radiolabeled monoclonal antibodies, such as yttrium Y 90 ibritumomab tiuxetan, can find cancer cells and carry cancer-killing substances to them without harming normal cells. Giving combination chemotherapy together with rituximab and yttrium Y 90 ibritumomab tiuxetan may kill more cancer cells.

PURPOSE: This phase II trial is studying giving combination chemotherapy followed by rituximab and yttrium Y 90 ibritumomab tiuxetan to see how well it works in treating patients with relapsed stage II, stage III, or stage IV follicular non-Hodgkin lymphoma.

OBJECTIVES:

Primary

* To evaluate the 1-year progression-free survival of patients with relapsed stage II-IV follicular non-Hodgkin lymphoma treated with ESHAP chemotherapy for cytoreduction followed by yttrium Y 90 ibritumomab tiuxetan radioimmunotherapy.
* To evaluate the median time to progression in these patients.

Secondary

* To evaluate the overall and complete response rates in patients treated with this regimen.

OUTLINE:

* ESHAP chemotherapy: Patients receive ESHAP chemotherapy comprising etoposide IV over 1 hour, methylprednisolone IV, cisplatin IV on days 1-4, and cytarabine IV over 2 hours on day 1. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity.
* Radioimmunotherapy: Between 4-6 weeks after completion of ESHAP chemotherapy, patients receive rituximab IV followed by indium In 111 ibritumomab tiuxetan IV over 10 minutes on day 1. Patients with \< 25% bone marrow involvement and expected biodistribution proceed to treatment. Patients receive rituximab IV followed by yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes on day 7, 8, or 9.

After completion of study treatment, patients are followed periodically.

Eligibility Criteria:
Inclusion Criteria:

* Diagnosis of follicular non-Hodgkin lymphoma (NHL)
* Bulky stage II, stage III, or stage IV disease, Bulky disease is defined as any tumor measuring 10.0 cm or more or occupying ≥ one-third of the chest diameter
* In first, second, third, or fourth relapse after chemotherapy
* Unilateral or bilateral bone marrow aspirate and biopsy with cytogenetics within the past 42 days
* Tumor CD20 positive by either flow cytometry or immunoperoxidase staining of paraffin sections using anti-CD20 antibodies
* Bidimensionally measurable disease
* Patients with non-measurable disease in addition to measurable disease must have all non-measurable disease assessed within the past 42 days
* No presence of CNS lymphoma
* No chronic lymphocytic leukemia
* No HIV- or AIDS-related lymphoma
* No presence of pleural effusion
* Zubrod performance status 0-2
* ANC ≥ 1,500/μL (unless decreased counts are due to marrow involvement with NHL)
* Platelet count \> 100,000/μL (unless decreased counts are due to marrow involvement with NHL)
* Serum creatinine ≤ 2.0 mg/dL
* Creatinine clearance ≤ 50 mL/min
* Serum bilirubin ≤ 2.0 mg/dL
* No renal insufficiency or renal failure
* No known HIV positivity
* Not pregnant or nursing
* No prior malignancy except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer with 5-year disease-free status
* No impaired bone marrow reserve, including any of the following:
* Hypocellular bone marrow (cellularity ≤ 15%)
* Marked ( ≥ 10%) reduction in bone marrow precursors of one or more cell lines (granulocytic, megakaryocytic, erythroid) (beyond that which would be expected for the patient's age and bone marrow cellularity)
* History of failed stem cell collection
* No serious, non-malignant disease or infection which, in the opinion of the investigator and/or sponsor, would compromise other protocol objectives
* At least 3 weeks since all prior therapy (6 weeks for rituximab) and recovered
* No prior myeloablative therapies with autologous bone marrow transplantation or peripheral blood stem cell rescue
* No prior radioimmunotherapy
* No prior external beam radiotherapy to \> 25% of active bone marrow (involved field or regional)
* More than 4 weeks since prior major surgery, other than diagnostic surgery

Exclusion Criteria

Patients with impaired bone marrow reserve, as indicated by one or more of the following:

* Platelet count \< 100,000 cells/mm3
* Hypocellular bone marrow (cellularity \< or = 10%)
* Marked (\> 10%) reduction in bone marrow precursors of one or more cell lines (granulocytic, megakaryocytic, erythroid) (beyond that which would be expected for the patient's age and bone marrow cellularity
* History of failed stem cell collection

Prior radioimmunotherapy

Presence of CNS lymphoma. Patients must not have clinical evidence of central nervous system (CNS) involvement by lymphoma.

Patients with abnormal liver function: total bilirubin \> 2.0 mg/dL

Patients with abnormal renal function: serum creatinine \> 2.0 mg/dL or creatinine clearance \< 50 ml/min.

Patients who have received prior external beam radiation therapy to \> 25% of active bone marrow (involved field or regional)

Patients who have received G-CSF or GM-CSF therapy within 2 weeks prior to treatment

Serious nonmalignant disease or infection which, in the opinion of the investigator and/or the sponsor, would compromise other protocol objectives

Major surgery, other than diagnostic surgery, within 4 weeks

Patients with pleural effusion