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

NCT ID: NCT00052884

Last Updated: 2023-06-18

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-01-22
• Study Completion Date: 2011-03-31

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.

Conditions

Drug/Agent Toxicity by Tissue/Organ; Multiple Myeloma and Plasma Cell Neoplasm

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Amifostine, Melphalan, and Stem Cell Reconstitution

Amifostine, Melphalan, and Stem Cell Reconstitution. Doses of Melphalan tested included 100 mg/m2 and 120 mg/m2

Group Type: EXPERIMENTAL

filgrastim

Intervention Type: BIOLOGICAL

amifostine trihydrate

Intervention Type: DRUG

melphalan

Intervention Type: DRUG

bone marrow ablation with stem cell support

Intervention Type: PROCEDURE

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

Interventions

filgrastim

Intervention Type: BIOLOGICAL

amifostine trihydrate

Intervention Type: DRUG

melphalan

Intervention Type: DRUG

bone marrow ablation with stem cell support

Intervention Type: PROCEDURE

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Eastern Cooperative Oncology Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Morie A. Gertz, MD

Role: STUDY_CHAIR

Mayo Clinic

Locations

Mayo Clinic Scottsdale

Scottsdale, Arizona, United States

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States

Fairview Ridges Hospital

Burnsville, Minnesota, United States

Mercy and Unity Cancer Center at Mercy Hospital

Coon Rapids, Minnesota, United States

Fairview Southdale Hospital

Edina, Minnesota, United States

Mercy and Unity Cancer Center at Unity Hospital

Fridley, Minnesota, United States

Minnesota Oncology Hematology, PA - Maplewood

Maplewood, Minnesota, United States

Virginia Piper Cancer Institute at Abbott - Northwestern Hospital

Minneapolis, Minnesota, United States

Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center

Robbinsdale, Minnesota, United States

Mayo Clinic Cancer Center

Rochester, 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

Minnesota Oncology Hematology, PA - Woodbury

Woodbury, Minnesota, United States

Case Comprehensive Cancer Center

Cleveland, Ohio, United States

Countries

United States

Other Identifiers

U10CA021115

Identifier Type: NIH

Identifier Source: secondary_id

View Link

ECOG-E2A01

Identifier Type: -

Identifier Source: secondary_id

CDR0000258785

Identifier Type: -

Identifier Source: org_study_id