A Phase I Trial of Zevalin Radioimmunotherapy With High-Dose Melphalan and Stem Cell Transplant for Multiple Myeloma
- 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.
- Determine the response rate and progression factors (time to progression,
progression-free survival, and duration of response) in patients treated with this
- 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.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Toxicity as measured by CTCAE v 3.0
Angela Dispenzieri, MD
United States: Food and Drug Administration
|Mayo Clinic||Rochester, Minnesota 55905|