A Phase I Study of Amifostine Followed by High-Dose Escalation of Melphalan With Stem Cell Reconstitution for Patients With Primary Systemic Amyloidosis
- Determine the maximum tolerated dose (MTD) of high-dose melphalan administered with
amifostine in patients with primary systemic amyloidosis undergoing autologous
peripheral blood stem cell transplantation.
- Determine the toxicity of high-dose melphalan when administered at the MTD in these
- Determine the response rate in patients treated with this regimen.
OUTLINE: This is a nonrandomized, multicenter, dose-escalation study of melphalan.
Patients receive filgrastim (G-CSF) subcutaneously once daily until peripheral blood stem
cell (PBSC) collection is complete. Apheresis begins on day 5 of G-CSF administration and
continues until the target number of PBSCs are collected.
Within 6 weeks of PBSC collection, patients receive amifostine IV over 5 minutes on days -2
and -1 and high-dose melphalan IV over 30-60 minutes on day -1. Patients undergo autologous
PBSC infusion on day 0.
Cohorts of 3-6 patients receive escalating doses of melphalan until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2
of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, an
additional 10 patients are treated at that dose.
Patients are followed approximately 3 months following transplantation, then every 6 months
for 5 years.
PROJECTED ACCRUAL: A total of 3-46 patients will be accrued for this study within 2.3 years.
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum Tolerated Dose
The maximum tolerated dose is the highest dose level at which fewer than 1 of 3 or 2 of 6 patients experience dose-limiting toxicity, defined as any grade 3 or higher toxicity of any of the following: renal failure, alkaline phosphatase elevation, GI bleeding, and cardiac rhythm disturbances, assessed using NCI Common Toxicity Criteria, version 2.0.
Assessed over 30 days
Morie A. Gertz, MD
United States: Federal Government
|Mayo Clinic Scottsdale||Scottsdale, Arizona 85259|
|Mayo Clinic Cancer Center||Rochester, Minnesota 55905|
|CCOP - Metro-Minnesota||Saint Louis Park, Minnesota 55416|
|Fairview Ridges Hospital||Burnsville, Minnesota 55337|
|Mercy and Unity Cancer Center at Mercy Hospital||Coon Rapids, Minnesota 55433|
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|Mercy and Unity Cancer Center at Unity Hospital||Fridley, Minnesota 55432|
|Minnesota Oncology Hematology, PA - Maplewood||Maplewood, Minnesota 55109|
|Virginia Piper Cancer Institute at Abbott - Northwestern Hospital||Minneapolis, Minnesota 55407|
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|Park Nicollet Cancer Center||St. Louis Park, Minnesota 55416|
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|Ridgeview Medical Center||Waconia, Minnesota 55387|
|Minnesota Oncology Hematology, PA - Woodbury||Woodbury, Minnesota 55125|
|Case Comprehensive Cancer Center||Cleveland, Ohio 44106-5065|
|Indiana University Melvin and Bren Simon Cancer Center||Indianapolis, Indiana 46202-5289|