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

Multiple Myeloma and Plasma Cell Neoplasm Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00052884
• Other study ID #: CDR0000258785
• Secondary ID: U10CA021115ECOG-
• Status: Terminated
• Phase: Phase 1
• Start date: January 22, 2004
• Est. completion date: March 2011

Study information

• Verified date: June 2023
• Source: Eastern Cooperative Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 8
• Est. completion date: March 2011
• Est. primary completion date: September 2007
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Amyloidosis
• Drug-Related Side Effects and Adverse Reactions
• Drug/Agent Toxicity by Tissue/Organ
• Immunoglobulin Light-chain Amyloidosis
• Multiple Myeloma
• Multiple Myeloma and Plasma Cell Neoplasm
• Neoplasms, Plasma Cell
• Plasmacytoma

Intervention

Biological:
• filgrastim

Drug:
• amifostine trihydrate

• melphalan

Procedure:
• bone marrow ablation with stem cell support

• peripheral blood stem cell transplantation

Locations

Country	Name	City	State
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Case Comprehensive Cancer Center	Cleveland	Ohio
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	Indiana University Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
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	Mayo Clinic Scottsdale	Scottsdale	Arizona
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Minnesota Oncology Hematology, PA - Woodbury	Woodbury	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Eastern Cooperative Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose	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.	Assessed over 30 days