Rituximab, Yttrium Y 90 Ibritumomab Tiuxetan, Melphalan, and Autologous Peripheral Stem Cell Transplant in Treating Patients With Previously Treated Multiple Myeloma

OBJECTIVES:

Primary

• Determine the safety of rituximab, yttrium Y 90 ibritumomab tiuxetan, high-dose melphalan, and autologous peripheral blood stem cell transplantation in patients with previously treated multiple myeloma.
• Determine the effect of rituximab and yttrium Y 90 ibritumomab tiuxetan on the clonotypic B-cells at baseline and at B-cell recovery in these patients.

Secondary

• Determine the response rate and progression factors (time to progression, progression-free survival, and duration of response) in patients treated with this regimen.
• Determine the effect of rituximab and yttrium Y 90 ibritumomab tiuxetan on the clonal plasma cells in the blood and marrow prior to high-dose melphalan.

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

Patients receive rituximab IV followed by a dosimetry dose of indium In 111 ibritumomab tiuxetan IV over 10 minutes on day -22. Patients with acceptable biodistribution receive rituximab IV followed by yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes on day -14, high-dose melphalan IV over 1 hour on days -2 and -1, and undergo autologous peripheral blood stem cell transplantation on day 0. Patients also receive sargramostim (GM-CSF) subcutaneously beginning on day 0 and continuing until blood counts recover.

Cohorts of 3-6 patients receive escalating doses of yttrium Y 90 ibritumomab tiuxetan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Bone marrow, blood, and urine samples are collected at baseline and then periodically during study for biomarker correlative studies.

After completion of study treatment, patients are followed every 3 months for 5 years.

DISEASE CHARACTERISTICS:

• Diagnosis of multiple myeloma

• Previously treated disease
• Candidate for high-dose chemotherapy with melphalan and autologous stem cell transplantation
• No definite evidence of myelodysplasia on pretreatment bone marrow by morphology or by chromosome analysis (e.g., monosomy 7)

• Chromosome abnormalities from the myeloma clone allowed

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• ANC ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Bilirubin ≤ 2.0 mg/dL
• Alkaline phosphatase ≤ 3 times upper limit of normal (ULN)
• AST ≤ 3 times ULN
• Creatinine ≤ 2 times ULN
• LVEF ≥ 45%
• Corrected pulmonary diffusion capacity ≥ 50%
• No uncontrolled infection
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other active malignancy (with the exception of nonmelanoma skin cancer) that requires myelosuppressive chemotherapy or radiation therapy
• No HIV positivity

PRIOR CONCURRENT THERAPY:

• More than 3 weeks since prior myelosuppressive chemotherapy, except cyclophosphamide pulsing for stem cell collection)
• No other concurrent immunotherapy, radiotherapy, chemotherapy or antimyeloma therapy
• Concurrent chronic corticosteroids at doses of prednisone ≤ 20 mg per day (or equivalent) allowed
• Concurrent adjuvant hormonal therapy (e.g., tamoxifen citrate or leuprolide acetate) allowed