Melphalan, Yttrium Y 90 Ibritumomab Tiuxetan, and Rituximab Followed by Autologous Stem Cell Transplant in Treating Older Patients With Non-Hodgkin's Lymphoma That Has Relapsed or Not Responded to Previous Treatment

OBJECTIVES:

• Determine the maximum tolerated dose of high-dose melphalan when given together with yttrium Y 90 ibritumomab tiuxetan and rituximab as a conditioning regimen followed by vinorelbine ditartrate- and filgrastim (G-CSF)-mobilized autologous stem cell transplantation in elderly patients with relapsed or refractory CD20-positive non-Hodgkin's lymphoma.
• Evaluate the feasibility and safety of this regimen in these patients.
• Determine the feasibility of stem cell mobilization with vinorelbine ditartrate in patients treated with this regimen.

OUTLINE: This is a multicenter, dose-escalation study of high-dose melphalan.

• Stem cell harvest and mobilization: Patients receive vinorelbine ditartrate IV on day -36 and filgrastim (G-CSF) subcutaneously (SC) twice daily on days -33 to -29. Patients undergo peripheral blood stem cell harvest on days -29 to -26.
• Radioimmunotherapy: Patients receive rituximab IV. Within 4 hours after completion of rituximab, patients receive indium In 111 ibritumomab tiuxetan (imaging dose) IV over 10 minutes on day -25. Patients undergo assessment of biodistribution, imaging, and dosimetry on days -25, -22, and optionally on day -20. Patients with acceptable biodistribution of indium In 111 ibritumomab tiuxetan receive rituximab IV followed by yttrium Y 90 ibritumomab tiuxetan (therapeutic dose) IV over 10 minutes on day -18.
• High-dose chemotherapy: Patients receive high-dose melphalan IV on day -1. Cohorts of 3-6 patients receive escalating doses of high-dose melphalan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.
• Autologous stem cell transplantation (ASCT): Patients undergo ASCT on day 0. Patients receive G-CSF SC beginning on day 5 and continuing until blood counts recover.

After completion of study treatment, patients are followed for 100 days.

PROJECTED ACCRUAL: A total of 24 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed non-Hodgkin's lymphoma of any type
• CD20-positive disease
• Achieved partial or complete response to salvage treatment for relapse or refractory disease within the past 10 weeks
• Must have an indication for autologous stem cell transplantation
• Bone marrow infiltration < 25%
• No evidence of CNS involvement

PATIENT CHARACTERISTICS:

• WHO performance status 0-1
• Bilirubin ≤ 2 times upper limit of normal (ULN)
• Alkaline phosphatase ≤ 2 times ULN
• AST ≤ 2 times ULN
• Creatinine clearance > 50 mL/min
• No clinically significant cardiac disease, including any of the following:

• Unstable angina pectoris
• Significant arrhythmia
• Myocardial infarction within the past 3 months
• LVEF > 50%
• No clinically significant urinary tract obstruction
• No clinically significant pulmonary disease
• No serious underlying medical condition that would preclude study participation
• No other malignancy within the past 5 years except nonmelanoma skin cancer or adequately treated in situ cervical cancer

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• At least 30 days since prior participation in another clinical trial
• No prior stem cell transplantation
• No prior radiolabeled antibodies, including for induction of disease remission
• No prior radiotherapy to ≥ 25% of the bone marrow
• No concurrent radiotherapy
• No other concurrent anticancer drugs
• No other concurrent investigational drugs