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A Phase I Study of Amifostine Followed by High-Dose Escalation of Melphalan With Stem Cell Reconstitution for Patients With Primary Systemic Amyloidosis

Phase 1
18 Years
70 Years
Not Enrolling
Drug/Agent Toxicity by Tissue/Organ, Multiple Myeloma and Plasma Cell Neoplasm

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Trial Information

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.

Inclusion Criteria


- Histologically confirmed amyloidosis

- No secondary familial or localized amyloidosis

- Presence of monoclonal protein by immunoelectrophoresis or immunofixation of serum or

- No primary amyloidosis manifested only by carpal tunnel syndrome or purpura

- Amyloid deposits in a plasmacytoma or in bone marrow vessels in an asymptomatic
individual not considered an amyloid syndrome

- Amyloid syndromes include any of the following:

- Hepatomegaly

- Cardiomyopathy

- Nephrotic range proteinuria

- Peripheral or autonomic neuropathy

- No multiple myeloma defined by 1 of the following:

- Presence of lytic bone disease

- More than 30% bone marrow plasma cells



- 18 to 70

Performance status

- ECOG 0-1

Life expectancy

- Not specified


- Platelet count at least 100,000/mm^3


- See Disease Characteristics

- Total or direct bilirubin no greater than 2.0 mg/dL

- Alkaline phosphatase no greater than 4 times upper limit of normal


- See Disease Characteristics

- Creatinine less than 3.0 mg/dL


- See Disease Characteristics

- Ejection fraction at least 45% by echocardiogram

- No New York Heart Association class III or IV heart disease

- Systolic blood pressure ≥ 90 mmHg


- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No active infection

- No other malignancy within the past 5 years except surgically treated carcinoma in
situ of the cervix, nonmelanoma skin cancer, or indolent prostate cancer


Biologic therapy

- At least 4 weeks since prior interferon


- At least 4 weeks since prior melphalan

- Lifetime total melphalan dose less than 150 mg/m^2 (based on ideal body weight)

Endocrine therapy

- At least 4 weeks since prior dexamethasone


- No prior radiotherapy for amyloidosis


- Not specified


- No antihypertensive medications for at least 24 hours prior to, during, and for 1
hour after amifostine administration

- No other prior treatment

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum Tolerated Dose

Outcome Description:

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.

Outcome Time Frame:

Assessed over 30 days

Safety Issue:


Principal Investigator

Morie A. Gertz, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Mayo Clinic


United States: Federal Government

Study ID:




Start Date:

October 2003

Completion Date:

March 2011

Related Keywords:

  • Drug/Agent Toxicity by Tissue/Organ
  • Multiple Myeloma and Plasma Cell Neoplasm
  • drug/agent toxicity by tissue/organ
  • primary systemic amyloidosis
  • Amyloidosis
  • Neoplasms
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Plasmacytoma



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
Fairview Southdale Hospital Edina, Minnesota  55435
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
Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center Robbinsdale, Minnesota  55422-2900
Park Nicollet Cancer Center St. Louis Park, Minnesota  55416
United Hospital St. Paul, Minnesota  55102
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