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

Sponsor

Eastern Cooperative Oncology Group (Other)

Overall Status

Terminated

CT.gov ID

NCT00052884

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Arm

Duration (Months)

0.5

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	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 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

8 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Oct 1, 2003

Actual Primary Completion Date :

Sep 1, 2007

Actual Study Completion Date :

Mar 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Amifostine, Melphalan, and Stem Cell Reconstitution Amifostine, Melphalan, and Stem Cell Reconstitution. Doses of Melphalan tested included 100 mg/m2 and 120 mg/m2	Biological: filgrastim Drug: amifostine trihydrate Drug: melphalan Procedure: bone marrow ablation with stem cell support Procedure: peripheral blood stem cell transplantation

Arm

Intervention/Treatment

Experimental: Amifostine, Melphalan, and Stem Cell Reconstitution

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

Biological: filgrastim

Drug: amifostine trihydrate

Drug: melphalan

Procedure: bone marrow ablation with stem cell support

Procedure: peripheral blood stem cell transplantation

Outcome Measures

Primary Outcome Measures

Maximum Tolerated Dose [Assessed over 30 days]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic Scottsdale	Scottsdale	Arizona	United States	85259-5499
2	Indiana University Melvin and Bren Simon Cancer Center	Indianapolis	Indiana	United States	46202-5289
3	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
4	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota	United States	55433
5	Fairview Southdale Hospital	Edina	Minnesota	United States	55435
6	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota	United States	55432
7	Minnesota Oncology Hematology, PA - Maplewood	Maplewood	Minnesota	United States	55109
8	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota	United States	55407
9	Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota	United States	55422-2900
10	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
11	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota	United States	55416
12	Park Nicollet Cancer Center	St. Louis Park	Minnesota	United States	55416
13	United Hospital	St. Paul	Minnesota	United States	55102
14	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
15	Minnesota Oncology Hematology, PA - Woodbury	Woodbury	Minnesota	United States	55125
16	Case Comprehensive Cancer Center	Cleveland	Ohio	United States	44106-5065