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

Sponsor:	Eastern Cooperative Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00052884

Purpose

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.

Condition	Intervention	Phase
Drug/Agent Toxicity by Tissue/Organ Multiple Myeloma and Plasma Cell Neoplasm	Biological: filgrastim Drug: amifostine trihydrate Drug: melphalan Procedure: bone marrow ablation with stem cell support Procedure: peripheral blood stem cell transplantation	Phase I

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Active Control
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

Resource links provided by NLM:

Genetics Home Reference related topics: aceruloplasminemia hemophilia transthyretin amyloidosis

MedlinePlus related topics: Amyloidosis Cancer Multiple Myeloma

Drug Information available for: Amifostine Filgrastim Melphalan Sarcolysin Melphalan hydrochloride

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Estimated Enrollment:	46
Study Start Date:	October 2003

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

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00052884

Locations

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
CCOP - Metro-Minnesota
Saint Louis Park, Minnesota, United States, 55416
Fairview Ridges Hospital
Burnsville, Minnesota, United States, 55337
Mercy and Unity Cancer Center at Mercy Hospital
Coon Rapids, Minnesota, United States, 55433
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
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
Minnesota Oncology Hematology, PA - Woodbury
Woodbury, Minnesota, United States, 55125
Park Nicollet Cancer Center
St. Louis Park, Minnesota, United States, 55416
Ridgeview Medical Center
Waconia, Minnesota, United States, 55387
United Hospital
St. Paul, Minnesota, United States, 55102
Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
Minneapolis, Minnesota, United States, 55407
United States, Ohio
Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44106-5065

Sponsors and Collaborators

Eastern Cooperative Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:	Morie A. Gertz, MD	Mayo Clinic
Investigator:	Philip R. Greipp, MD	Mayo Clinic

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000258785, ECOG-E2A01
Study First Received:	January 24, 2003
Last Updated:	May 9, 2009
ClinicalTrials.gov Identifier:	NCT00052884 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

drug/agent toxicity by tissue/organ
primary systemic amyloidosis

Additional relevant MeSH terms:

Melphalan
Radiation-Protective Agents
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Blood Protein Disorders
Physiological Effects of Drugs
Paraproteinemias
Hemostatic Disorders
Hemorrhagic Disorders
Therapeutic Uses
Cardiovascular Diseases
Alkylating Agents
Neoplasms by Histologic Type
Metabolic Diseases

Immunoproliferative Disorders
Immune System Diseases
Amifostine
Hematologic Diseases
Vascular Diseases
Protective Agents
Immunosuppressive Agents
Pharmacologic Actions
Multiple Myeloma
Neoplasms
Amyloidosis
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Lymphoproliferative Disorders
Neoplasms, Plasma Cell

ClinicalTrials.gov processed this record on February 08, 2010