Amifostine and Melphalan in Treating Patients With Primary Systemic Amyloidosis Who Are Undergoing Peripheral Stem Cell Transplantation
RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of plasma cells, either by killing the cells or by stopping them from dividing. Having a peripheral stem cell transplant to replace the blood-forming cells destroyed by chemotherapy, allows higher dose of chemotherapy to be given so that more plasma cells are killed. Giving a chemoprotective drug such as amifostine may protect kidney cells from the side effects of chemotherapy.
PURPOSE: This phase I trial is studying the side effects and best dose of melphalan given together with amifostine in treating patients who are undergoing peripheral stem cell transplant for primary systemic amyloidosis.
Drug/Agent Toxicity by Tissue/Organ
Multiple Myeloma and Plasma Cell Neoplasm
Drug: amifostine trihydrate
Procedure: bone marrow ablation with stem cell support
Procedure: peripheral blood stem cell transplantation
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Study of Amifostine Followed by High-Dose Escalation of Melphalan With Stem Cell Reconstitution for Patients With Primary Systemic Amyloidosis|
- Maximum Tolerated Dose [ Time Frame: Assessed over 30 days ] [ Designated as safety issue: Yes ]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.
|Study Start Date:||October 2003|
|Study Completion Date:||March 2011|
|Primary Completion Date:||September 2007 (Final data collection date for primary outcome measure)|
Experimental: Amifostine, Melphalan, and Stem Cell Reconstitution
Amifostine, Melphalan, and Stem Cell Reconstitution. Doses of Melphalan tested included 100 mg/m2 and 120 mg/m2
|Biological: filgrastim Drug: amifostine trihydrate Drug: melphalan Procedure: bone marrow ablation with stem cell support Procedure: peripheral blood stem cell transplantation|
- 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 patients.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00052884
|United States, Arizona|
|Mayo Clinic Scottsdale|
|Scottsdale, Arizona, United States, 85259-5499|
|United States, Indiana|
|Indiana University Melvin and Bren Simon Cancer Center|
|Indianapolis, Indiana, United States, 46202-5289|
|United States, Minnesota|
|Fairview Ridges Hospital|
|Burnsville, Minnesota, United States, 55337|
|Mercy and Unity Cancer Center at Mercy Hospital|
|Coon Rapids, Minnesota, United States, 55433|
|Fairview Southdale Hospital|
|Edina, Minnesota, United States, 55435|
|Mercy and Unity Cancer Center at Unity Hospital|
|Fridley, Minnesota, United States, 55432|
|Minnesota Oncology Hematology, PA - Maplewood|
|Maplewood, Minnesota, United States, 55109|
|Virginia Piper Cancer Institute at Abbott - Northwestern Hospital|
|Minneapolis, Minnesota, United States, 55407|
|Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center|
|Robbinsdale, Minnesota, United States, 55422-2900|
|Mayo Clinic Cancer Center|
|Rochester, Minnesota, United States, 55905|
|CCOP - Metro-Minnesota|
|Saint Louis Park, Minnesota, United States, 55416|
|Park Nicollet Cancer Center|
|St. Louis Park, Minnesota, United States, 55416|
|St. Paul, Minnesota, United States, 55102|
|Ridgeview Medical Center|
|Waconia, Minnesota, United States, 55387|
|Minnesota Oncology Hematology, PA - Woodbury|
|Woodbury, Minnesota, United States, 55125|
|United States, Ohio|
|Case Comprehensive Cancer Center|
|Cleveland, Ohio, United States, 44106-5065|
|Study Chair:||Morie A. Gertz, MD||Mayo Clinic|