Melphalan, Thalidomide, and Dexamethasone in Treating Patients With Newly Diagnosed, Previously Untreated Primary Systemic Amyloidosis

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00089167

Collaborator

National Cancer Institute (NCI) (NIH)

Location

Study Details

Study Description

Brief Summary

RATIONALE: Drugs such as melphalan, thalidomide, and dexamethasone may be effective in treating patients with primary systemic amyloidosis.

PURPOSE: This phase II trial is studying how well giving melphalan together with thalidomide and dexamethasone works in treating patients with primary systemic amyloidosis.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma and Plasma Cell Neoplasm	Biological: filgrastim Drug: dexamethasone Drug: melphalan Drug: thalidomide	Phase 2

Detailed Description

OBJECTIVES:

Primary

Determine the 2-year and overall progression-free survival of patients with newly diagnosed, previously untreated primary systemic (AL) amyloidosis treated with risk-adapted melphalan followed by thalidomide and dexamethasone.

Secondary

Determine plasma cell disease response in these patients at 3, 12, and 24 months after treatment with this regimen.
Determine amyloid-related disease response in these patients at 12 and 24 months after treatment with this regimen.
Determine the prognostic significance of immunoglobulin light-chain variable-region germline gene expression by AL plasma cell clones in patients treated with this regimen.
Determine whether there is molecular minimal residual disease at 12 and 24 months in patients achieving a complete hematologic response after treatment with this regimen.

OUTLINE: Patients are stratified according to the extent of amyloid-related disease (low-risk vs high-risk).

High-risk disease: Patients receive 2 courses of low-dose melphalan IV, dexamethasone, and filgrastim (G-CSF). After 3 months, patients receive thalidomide and dexamethasone if plasma cell disease persists.
Low-risk disease: Patients receive 1 course of high-dose melphalan IV and G-CSF. Patients then receive thalidomide and dexamethasone as in high-risk disease regimen.

Patients are followed at 3, 12, and 24 months.

PROJECTED ACCRUAL: A total of 82 patients will be accrued for this study.

Study Design

Study Type:

Interventional

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Risk Adapted Intravenous Melphalan and Adjuvant Thalidomide and Dexamethasone for Untreated Patients With Primary Systemic Amyloidosis

Study Start Date :

May 1, 2002

Actual Primary Completion Date :

Dec 1, 2007

Outcome Measures

Primary Outcome Measures

Overall progression-free survival at 2 years []

Secondary Outcome Measures

Plasma cell disease response at 3, 12, and 24 months after treatment []
Amyloid-related disease response at 12 and 24 months after treatment []
Prognostic significance of immunoglobulin light-chain variable-region germline gene expression by AL cell clones []
Molecular minimal residual disease at 12 and 24 months []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Diagnosis of primary systemic (AL) amyloidosis within the past 12 months
High- or low-risk disease, determined by the extent of systemic organ involvement with disease and patient age

PATIENT CHARACTERISTICS:

Age

18 and over

Performance status

SWOG 0-3

Life expectancy

Not specified

Hematopoietic

Not specified

Hepatic

Not specified

Renal

Not specified

Cardiovascular

No New York Heart Association class III or IV congestive heart failure
No restrictive cardiomyopathy requiring oxygen
No myocardial infarction within the past 6 months
No symptomatic cardiac arrhythmia within the past 60 days

Other

No other active malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I cancer in complete remission

PRIOR CONCURRENT THERAPY:

Biologic therapy

Not specified

Chemotherapy

No prior chemotherapy for AL amyloidosis

Endocrine therapy

Not specified

Radiotherapy

Not specified

Surgery

Not specified

Other

No other prior or concurrent therapy for AL amyloidosis

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10021

Sponsors and Collaborators

Memorial Sloan Kettering Cancer Center
National Cancer Institute (NCI)

Investigators

Principal Investigator: Raymond L. Comenzo, MD, Memorial Sloan Kettering Cancer Center
Principal Investigator: Madhav Dhodapkar, MD, Memorial Sloan Kettering Cancer Center