Amifostine and Melphalan in Treating Patients With Primary Systemic Amyloidosis Who Are Undergoing Peripheral Stem Cell Transplantation
Information source: National Cancer Institute (NCI)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Drug/Agent Toxicity by Tissue/Organ; Multiple Myeloma and Plasma Cell Neoplasm
Intervention: amifostine trihydrate (Drug); filgrastim (Drug); melphalan (Drug); bone marrow ablation with stem cell support (Procedure); peripheral blood stem cell transplantation (Procedure)
Phase: Phase 1
Status: Active, not recruiting
Sponsored by: Eastern Cooperative Oncology Group Official(s) and/or principal investigator(s):
Morie A. Gertz, MD, Study Chair, Affiliation: Mayo Clinic
Philip R. Greipp, MD, Affiliation: Mayo Clinic
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.
Clinical Details
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
Study design: Treatment, Non-Randomized, Active Control
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.
Eligibility
Minimum age: 18 Years.
Maximum age: 70 Years.
Gender(s): Both.
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
Locations and Contacts
Mayo Clinic Scottsdale, Scottsdale, Arizona 85259-5499, United States
Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana 46202-5289, United States
CCOP - Metro-Minnesota, Saint Louis Park, Minnesota 55416, United States
Fairview Ridges Hospital, Burnsville, Minnesota 55337, United States
Fairview Southdale Hospital, Edina, Minnesota 55435, United States
Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center, Robbinsdale, Minnesota 55422-2900, United States
Mayo Clinic Cancer Center, Rochester, Minnesota 55905, United States
Mercy and Unity Cancer Center at Mercy Hospital, Coon Rapids, Minnesota 55433, United States
Mercy and Unity Cancer Center at Unity Hospital, Fridley, Minnesota 55432, United States
Minnesota Oncology Hematology, PA - Maplewood, Maplewood, Minnesota 55109, United States
Minnesota Oncology Hematology, PA - Woodbury, Woodbury, Minnesota 55125, United States
Park Nicollet Cancer Center, St. Louis Park, Minnesota 55416, United States
Ridgeview Medical Center, Waconia, Minnesota 55387, United States
United Hospital, St. Paul, Minnesota 55102, United States
Virginia Piper Cancer Institute at Abbott - Northwestern Hospital, Minneapolis, Minnesota 55407, United States
Case Comprehensive Cancer Center, Cleveland, Ohio 44106-5065, United States
Additional Information
Clinical trial summary from the National Cancer Institute's PDQ® database
Starting date: October 2003
Last updated: June 17, 2008
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