Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Supportive care, Treatment	Closed	18 to 70	NCI, Other	CDR0000258785 ECOG-E2A01, NCT00052884

Trial Description

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.

Further Study Information

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 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

Trial Contact Information

Trial Lead Organizations/Sponsors

Eastern Cooperative Oncology Group

Morie Abraham Gertz

Study Chair

Philip R. Greipp

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00052884
Information obtained from ClinicalTrials.gov on December 06, 2009

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