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Amifostine and Melphalan in Treating Patients With Primary Systemic Amyloidosis Who Are Undergoing Peripheral Stem Cell Transplantation

Phase 1
Terminated
Conditions
Multiple Myeloma and Plasma Cell Neoplasm
Drug/Agent Toxicity by Tissue/Organ
Interventions
Biological: filgrastim
Procedure: bone marrow ablation with stem cell support
Procedure: peripheral blood stem cell transplantation
Registration Number
NCT00052884
Lead Sponsor
Eastern Cooperative Oncology Group
Brief Summary

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.

Detailed Description

OBJECTIVES:

* 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.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
8
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Amifostine, Melphalan, and Stem Cell Reconstitutionamifostine trihydrateAmifostine, Melphalan, and Stem Cell Reconstitution. Doses of Melphalan tested included 100 mg/m2 and 120 mg/m2
Amifostine, Melphalan, and Stem Cell Reconstitutionbone marrow ablation with stem cell supportAmifostine, Melphalan, and Stem Cell Reconstitution. Doses of Melphalan tested included 100 mg/m2 and 120 mg/m2
Amifostine, Melphalan, and Stem Cell Reconstitutionperipheral blood stem cell transplantationAmifostine, Melphalan, and Stem Cell Reconstitution. Doses of Melphalan tested included 100 mg/m2 and 120 mg/m2
Amifostine, Melphalan, and Stem Cell ReconstitutionfilgrastimAmifostine, Melphalan, and Stem Cell Reconstitution. Doses of Melphalan tested included 100 mg/m2 and 120 mg/m2
Amifostine, Melphalan, and Stem Cell ReconstitutionmelphalanAmifostine, Melphalan, and Stem Cell Reconstitution. Doses of Melphalan tested included 100 mg/m2 and 120 mg/m2
Primary Outcome Measures
NameTimeMethod
Maximum Tolerated DoseAssessed over 30 days

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.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (16)

Mercy and Unity Cancer Center at Mercy Hospital

🇺🇸

Coon Rapids, Minnesota, United States

Minnesota Oncology Hematology, PA - Woodbury

🇺🇸

Woodbury, Minnesota, United States

Mayo Clinic Scottsdale

🇺🇸

Scottsdale, Arizona, United States

Virginia Piper Cancer Institute at Abbott - Northwestern Hospital

🇺🇸

Minneapolis, Minnesota, United States

Case Comprehensive Cancer Center

🇺🇸

Cleveland, Ohio, United States

Fairview Ridges Hospital

🇺🇸

Burnsville, Minnesota, United States

Indiana University Melvin and Bren Simon Cancer Center

🇺🇸

Indianapolis, Indiana, United States

Fairview Southdale Hospital

🇺🇸

Edina, Minnesota, United States

Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center

🇺🇸

Robbinsdale, Minnesota, United States

Mercy and Unity Cancer Center at Unity Hospital

🇺🇸

Fridley, Minnesota, United States

Mayo Clinic Cancer Center

🇺🇸

Rochester, Minnesota, United States

Minnesota Oncology Hematology, PA - Maplewood

🇺🇸

Maplewood, Minnesota, United States

CCOP - Metro-Minnesota

🇺🇸

Saint Louis Park, Minnesota, United States

Park Nicollet Cancer Center

🇺🇸

Saint Louis Park, Minnesota, United States

United Hospital

🇺🇸

Saint Paul, Minnesota, United States

Ridgeview Medical Center

🇺🇸

Waconia, Minnesota, United States

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