Radiolabeled Monoclonal Antibody Therapy and High-Dose Chemotherapy Followed By Autologous Peripheral Stem Cell Transplant in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma

OBJECTIVES:

• Determine the maximum tolerated dose of yttrium Y 90 ibritumomab tiuxetan, in terms of absorbed radiation to critical organs, when administered with high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma.
• Determine whether the residual radioactivity detected at the time of stem cell reinfusion affects the reinfused cells and delays engraftment in patients treated with this regimen.
• Determine the duration of response and survival of patients treated with this regimen.

OUTLINE: This is a dose-escalation study of yttrium Y 90 ibritumomab tiuxetan (IDEC-Y2B8).

• Radioimmunotherapy: Patients receive rituximab IV followed by indium In 111 ibritumomab tiuxetan (for imaging) IV over 10 minutes on day -22. Patients then receive rituximab IV and IDEC-Y2B8 IV over 10 minutes on day -14.

Cohorts of 3-6 patients receive escalating doses of IDEC-Y2B8 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 3 of 6 patients experience dose-limiting toxicity.

• High-dose conditioning regimen: Patients receive BEAM chemotherapy comprising carmustine IV over 2 hours on day -6, etoposide IV over 2 hours twice daily and cytarabine IV over 1 hour twice daily on days -5 to -2, and melphalan IV over 1 hour on day -1.
• Autologous stem cell transplantation: Autologous peripheral blood stem cells are reinfused on day 0. Patients receive filgrastim (G-CSF) subcutaneously daily beginning on day 0 and continuing until blood counts recover.

Patients are followed at 30 days, 3 and 6 months, and then annually for 5 years.

PROJECTED ACCRUAL: A maximum of 42 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed B-cell non-Hodgkin's lymphoma

• Relapsed or refractory disease
• CD20-positive disease
• Must have received at least 1 prior treatment regimen
• Complete remission with prior conventional salvage chemotherapy is allowed
• No more than 25% lymphoma in bone marrow
• No circulating malignant cells on blood smear
• No CNS involvement by lymphoma
• No HIV- or AIDS-related lymphoma

PATIENT CHARACTERISTICS:

Age

• Over 17

Performance status

• ECOG 0-2

Life expectancy

• At least 3 months

Hematopoietic

• Platelet count at least 100,000/mm^3
• Absolute neutrophil count at least 1,500/mm^3

Hepatic

• Transaminases less than 2 times normal

Renal

• Creatinine clearance greater than 50 mL/min

Cardiovascular

• LVEF at least 45%

Pulmonary

• Corrected DLCO at least 70% of predicted
• FEV_1 or FVC greater than 60%

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No active infection
• No serious nonmalignant disease or other condition that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• More than 4 weeks since prior rituximab and recovered
• No other prior murine antibodies
• No prior stem cell transplantation
• No prior radioimmunoconjugate therapy

Chemotherapy

• See Disease Characteristics
• More than 6 weeks since prior nitrosoureas or mitomycin and recovered

Endocrine therapy

• No concurrent systemic corticosteroids

Radiotherapy

• Recovered from prior radiotherapy
• No prior external beam irradiation to more than 25% of the active bone marrow

Surgery

• More than 4 weeks since prior major surgery and recovered

Other

• More than 3 weeks since prior anticancer therapy