A Phase I Trial of Zevalin Radioimmunotherapy With High-Dose Melphalan and Stem Cell Transplant for Multiple Myeloma
18 Years
N/A
Both
Multiple Myeloma and Plasma Cell Neoplasm
Trial Information
A Phase I Trial of Zevalin Radioimmunotherapy With High-Dose Melphalan and Stem Cell Transplant for 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.
Inclusion Criteria
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
Type of Study:
Interventional
Study Design:
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Toxicity as measured by CTCAE v 3.0
Outcome Time Frame:
19 Months
Safety Issue:
Yes
Principal Investigator
Angela Dispenzieri, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Mayo Clinic
Authority:
United States: Food and Drug Administration
Study ID:
CDR0000546732
NCT ID:
NCT00477815
Start Date:
May 2005
Completion Date:
Related Keywords:
- Multiple Myeloma and Plasma Cell Neoplasm
- stage I multiple myeloma
- refractory multiple myeloma
- stage II multiple myeloma
- stage III multiple myeloma
- Neoplasms
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Plasmacytoma
Name | Location |
|---|---|
| Mayo Clinic | Rochester, Minnesota 55905 |
