A Phase I Study of Amifostine Followed by High-Dose Escalation of Melphalan With Stem Cell Reconstitution for Patients With Primary Systemic Amyloidosis
18 Years
70 Years
Both
Drug/Agent Toxicity by Tissue/Organ, Multiple Myeloma and Plasma Cell Neoplasm
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
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.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed amyloidosis
- No secondary familial or localized amyloidosis
- Presence of monoclonal protein by immunoelectrophoresis or immunofixation of serum or
urine
- 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
PATIENT CHARACTERISTICS:
Age
- 18 to 70
Performance status
- ECOG 0-1
Life expectancy
- Not specified
Hematopoietic
- Platelet count at least 100,000/mm^3
Hepatic
- 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
Renal
- See Disease Characteristics
- Creatinine less than 3.0 mg/dL
Cardiovascular
- 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
Other
- 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
PRIOR CONCURRENT THERAPY:
Biologic therapy
- At least 4 weeks since prior interferon
Chemotherapy
- 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
Radiotherapy
- No prior radiotherapy for amyloidosis
Surgery
- Not specified
Other
- 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:
Interventional
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:
Yes
Principal Investigator
Morie A. Gertz, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Mayo Clinic
Authority:
United States: Federal Government
Study ID:
CDR0000258785
NCT ID:
NCT00052884
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
Name | Location |
|---|---|
| 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 |
