- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01078454
Melphalan and Dexamethasone With or Without Bortezomib in Treating Patients With Previously Untreated Systemic Light-Chain Amyloidosis
A Randomized Phase III Trial of Melphalan and Dexamethasone (MDex) Versus Bortezomib, Melphalan and Dexamethasone (BMDex) for Untreated Patients With Systemic Light-Chain (AL) Amyloidosis Ineligible for Autologous Stem-Cell Transplantation
Study Overview
Status
Intervention / Treatment
Detailed Description
PRIMARY OBJECTIVES:
I. To compare hematologic overall response (partial response [PR], very good PR, amyloid complete hematologic response [ACR], and stringent complete response [sCR]) after 3 courses of therapy in patients with previously untreated systemic light-chain amyloidosis treated with melphalan and dexamethasone with vs without bortezomib.
SECONDARY OBJECTIVES:
I. To evaluate the ACR rate after 3 courses of therapy and at completion of therapy.
II. To evaluate organ response rates after 3 courses of therapy and at 6, 9, and 12 months.
III. To evaluate treatment-related mortality.
IV. To evaluate toxicity.
V. To evaluate progression-free and overall survival.
VI. To evaluate PR or better at completion of therapy.
VII. To evaluate time to hematologic and organ response.
VIII. To evaluate the duration of hematologic and organ response.
IX. To assess quality of life (QOL) at baseline, at 3, 6, and 9 months during the therapy, at completion of therapy, and 3 and 6 months after therapy.
TERTIARY OBJECTIVES:
I. To determine the prognostic impact of t(11;14) translocation and cyclin D1 overexpression on response and overall survival.
II. (Correlative) To compare sCR rates and to determine the impact of sCR on the outcomes.
III. (Correlative) To perform a descriptive analysis of amyloid typing and proteomic composition of amyloid tissues.
OUTLINE: This is a multicenter study. Patients are stratified according to amyloid cardiac stage (stage I/II vs. better risk stage III) and are randomized to 1 of 2 treatment arms.
ARM A (Mel-Dex): Patients receive melphalan 0.22 mg/kg orally (PO) and dexamethasone 40 mg PO on days 1-4 every 4 weeks. Treatment repeats every 4 weeks for up to 9 courses in the absence of disease progression or unacceptable toxicity.
ARM B (B-Mel-Dex): Patients receive melphalan 0.22 mg/kg PO and dexamethasone 40 mg PO on days 1-4 and bortezomib 1.3 mg/m2 intravenously (IV) on days 1, 4, 8, and 11 every 4 weeks. Treatment repeats every 4 weeks for 2 cycles. Patients then receive melphalan PO and dexamethasone PO on days 1-4 and bortezomib IV on days 1, 8, 15, and 22 every 5 weeks. Treatment repeats every 5 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
Blood, urine, bone marrow, and fat samples may be collected periodically for laboratory analysis. Health-related quality of life is assessed periodically before, during, and after therapy. After completion of study treatment, patients are followed up periodically for 5 years.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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Arizona
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Scottsdale, Arizona, United States, 85259
- Mayo Clinic in Arizona
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Arkansas
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Little Rock, Arkansas, United States, 72205
- University of Arkansas for Medical Sciences
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Colorado
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Aurora, Colorado, United States, 80012
- The Medical Center of Aurora
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Boulder, Colorado, United States, 80301
- Boulder Community Hospital
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Colorado Springs, Colorado, United States, 80907
- Penrose-Saint Francis Healthcare
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Denver, Colorado, United States, 80210
- Porter Adventist Hospital
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Denver, Colorado, United States, 80218
- Presbyterian - Saint Lukes Medical Center - Health One
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Denver, Colorado, United States, 80220
- Rose Medical Center
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Denver, Colorado, United States, 80218
- Exempla Saint Joseph Hospital
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Denver, Colorado, United States, 80224-2522
- Colorado Cancer Research Program CCOP
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Englewood, Colorado, United States, 80113
- Swedish Medical Center
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Grand Junction, Colorado, United States, 81502
- Saint Mary's Hospital and Regional Medical Center
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Greeley, Colorado, United States, 80631
- North Colorado Medical Center
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Lakewood, Colorado, United States, 80228
- Saint Anthony Hospital
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Littleton, Colorado, United States, 80122
- Littleton Adventist Hospital
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Lone Tree, Colorado, United States, 80124
- Sky Ridge Medical Center
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Longmont, Colorado, United States, 80501
- Longmont United Hospital
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Loveland, Colorado, United States, 80539
- McKee Medical Center
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Parker, Colorado, United States, 80138
- Parker Adventist Hospital
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Pueblo, Colorado, United States, 81004
- Saint Mary Corwin Medical Center
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Thornton, Colorado, United States, 80229
- North Suburban Medical Center
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Wheat Ridge, Colorado, United States, 80033
- Exempla Lutheran Medical Center
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Connecticut
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Norwich, Connecticut, United States, 06360
- Eastern Connecticut Hematology and Oncology Associates
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Delaware
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Lewes, Delaware, United States, 19958
- Beebe Medical Center
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Newark, Delaware, United States, 19718
- Christiana Care Health System-Christiana Hospital
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Florida
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Jacksonville, Florida, United States, 32224-9980
- Mayo Clinic in Florida
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Weston, Florida, United States, 33331
- Cleveland Clinic Florida - Weston
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Georgia
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Atlanta, Georgia, United States, 30322
- Emory University/Winship Cancer Institute
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Hawaii
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'Aiea, Hawaii, United States, 96701
- Pali Momi Medical Center
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'Aiea, Hawaii, United States, 96701
- Oncare Hawaii Inc-Pali Momi
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Honolulu, Hawaii, United States, 96813
- Queen's Medical Center
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Honolulu, Hawaii, United States, 96813
- Straub Clinic and Hospital
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Honolulu, Hawaii, United States, 96817
- Kuakini Medical Center
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Honolulu, Hawaii, United States, 96826
- Kapiolani Medical Center for Women and Children
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Honolulu, Hawaii, United States, 96813
- University of Hawaii
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Honolulu, Hawaii, United States, 96813
- Oncare Hawaii Inc-POB II
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Honolulu, Hawaii, United States, 96817-3169
- OnCare Hawaii-Liliha
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Honolulu, Hawaii, United States, 96817
- Oncare Hawaii Inc-Kuakini
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Kailua, Hawaii, United States, 96734
- Castle Medical Center
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Lihue, Hawaii, United States, 96766
- Wilcox Memorial Hospital and Kauai Medical Clinic
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Illinois
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Bloomington, Illinois, United States, 61701
- Saint Joseph Medical Center
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Bloomington, Illinois, United States, 61701
- Illinois CancerCare-Bloomington
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Canton, Illinois, United States, 61520
- Illinois CancerCare-Canton
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Canton, Illinois, United States, 61520
- Graham Hospital Association
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Carthage, Illinois, United States, 62321
- Illinois CancerCare-Carthage
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Carthage, Illinois, United States, 62321
- Memorial Hospital
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Decatur, Illinois, United States, 62526
- Decatur Memorial Hospital
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Eureka, Illinois, United States, 61530
- Illinois CancerCare-Eureka
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Eureka, Illinois, United States, 61530
- Eureka Hospital
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Galesburg, Illinois, United States, 61401
- Illinois CancerCare Galesburg
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Havana, Illinois, United States, 62644
- Mason District Hospital
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Havana, Illinois, United States, 62644
- Illinois CancerCare-Havana
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Kewanee, Illinois, United States, 61443
- Illinois CancerCare-Kewanee Clinic
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Macomb, Illinois, United States, 61455
- Illinois CancerCare-Macomb
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Macomb, Illinois, United States, 61455
- McDonough District Hospital
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Monmouth, Illinois, United States, 61462
- Illinois CancerCare-Monmouth
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Monmouth, Illinois, United States, 61462
- Holy Family Medical Center
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Normal, Illinois, United States, 61761
- Community Cancer Center Foundation
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Normal, Illinois, United States, 61761
- BroMenn Regional Medical Center
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Normal, Illinois, United States, 61761
- Illinois CancerCare-Community Cancer Center
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Ottawa, Illinois, United States, 61350
- Illinois CancerCare-Ottawa Clinic
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Ottawa, Illinois, United States, 61350
- Ottawa Regional Hospital and Healthcare Center
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Pekin, Illinois, United States, 61554
- Pekin Cancer Treatment Center
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Pekin, Illinois, United States, 61603
- Illinois CancerCare-Pekin
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Peoria, Illinois, United States, 61637
- OSF Saint Francis Medical Center
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Peoria, Illinois, United States, 61615
- Illinois CancerCare-Peoria
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Peoria, Illinois, United States, 61614
- Proctor Hospital
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Peoria, Illinois, United States, 61603
- Methodist Medical Center of Illinois
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Peoria, Illinois, United States, 61615
- Illinois Oncology Research Association CCOP
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Peru, Illinois, United States, 61354
- Illinois CancerCare-Peru
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Peru, Illinois, United States, 61354
- Illinois Valley Hospital
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Princeton, Illinois, United States, 61356
- Illinois CancerCare-Princeton
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Princeton, Illinois, United States, 61356
- Perry Memorial Hospital
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Spring Valley, Illinois, United States, 61362
- Illinois CancerCare-Spring Valley
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Springfield, Illinois, United States, 62781-0001
- Memorial Medical Center
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Indiana
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Beech Grove, Indiana, United States, 46107
- Saint Francis Hospital and Health Centers
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Indianapolis, Indiana, United States, 46202
- Indiana University Medical Center
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Richmond, Indiana, United States, 47374
- Reid Hospital and Health Care Services
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Iowa
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Ames, Iowa, United States, 50010
- McFarland Clinic PC-William R Bliss Cancer Center
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Iowa City, Iowa, United States, 52242
- University of Iowa Hospitals and Clinics
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Sioux City, Iowa, United States, 51104
- Saint Luke's Regional Medical Center
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Sioux City, Iowa, United States, 51101
- Siouxland Hematology Oncology Associates
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Sioux City, Iowa, United States, 51104
- Mercy Medical Center-Sioux City
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Maryland
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Elkton, Maryland, United States, 21921
- Union Hospital of Cecil County
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Massachusetts
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Boston, Massachusetts, United States, 02111
- Tufts Medical Center
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Boston, Massachusetts, United States, 02118
- Boston Medical Center
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Michigan
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Ann Arbor, Michigan, United States, 48109
- University of Michigan
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Detroit, Michigan, United States, 48201
- Wayne State University/Karmanos Cancer Institute
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Escanaba, Michigan, United States, 49431
- Green Bay Oncology - Escanaba
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Iron Mountain, Michigan, United States, 49801
- Green Bay Oncology - Iron Mountain
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Kalamazoo, Michigan, United States, 49007
- West Michigan Cancer Center
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Kalamazoo, Michigan, United States, 49007
- Bronson Methodist Hospital
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Kalamazoo, Michigan, United States, 49001
- Borgess Medical Center
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Southfield, Michigan, United States, 48075
- Providence Hospital
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Minnesota
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Burnsville, Minnesota, United States, 55337
- Fairview Ridges Hospital
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Coon Rapids, Minnesota, United States, 55433
- Mercy Hospital
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Edina, Minnesota, United States, 55435
- Fairview-Southdale Hospital
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Fridley, Minnesota, United States, 55432
- Unity Hospital
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Hutchinson, Minnesota, United States, 55350
- Hutchinson Area Health Care
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Maplewood, Minnesota, United States, 55109
- Saint John's Hospital - Healtheast
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Maplewood, Minnesota, United States, 55109
- Minnesota Oncology Hematology PA-Maplewood
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Minneapolis, Minnesota, United States, 55415
- Hennepin County Medical Center
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Minneapolis, Minnesota, United States, 55407
- Abbott-Northwestern Hospital
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New Ulm, Minnesota, United States, 56073
- New Ulm Medical Center
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Robbinsdale, Minnesota, United States, 55422
- North Memorial Medical Health Center
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Rochester, Minnesota, United States, 55905
- Mayo Clinic
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Saint Louis Park, Minnesota, United States, 55416
- Park Nicollet Clinic - Saint Louis Park
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Saint Louis Park, Minnesota, United States, 55416
- Metro-Minnesota CCOP
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Saint Paul, Minnesota, United States, 55101
- Regions Hospital
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Saint Paul, Minnesota, United States, 55102
- United Hospital
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Shakopee, Minnesota, United States, 55379
- Saint Francis Regional Medical Center
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Stillwater, Minnesota, United States, 55082
- Lakeview Hospital
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Waconia, Minnesota, United States, 55387
- Ridgeview Medical Center
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Willmar, Minnesota, United States, 56201
- Rice Memorial Hospital
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Woodbury, Minnesota, United States, 55125
- Minnesota Oncology and Hematology PA-Woodbury
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Mississippi
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Jackson, Mississippi, United States, 39216
- University of Mississippi Medical Center
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Missouri
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Saint Louis, Missouri, United States, 63110
- Washington University School of Medicine
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Montana
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Billings, Montana, United States, 59101
- Saint Vincent Healthcare
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Billings, Montana, United States, 59101
- Montana Cancer Consortium CCOP
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Billings, Montana, United States, 59102
- Hematology-Oncology Centers of the Northern Rockies PC
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Billings, Montana, United States, 59107-7000
- Billings Clinic
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Bozeman, Montana, United States, 59715
- Bozeman Deaconess Hospital
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Bozeman, Montana, United States, 59715
- Bozeman Deaconess Cancer Center
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Butte, Montana, United States, 59701
- Saint James Community Hospital and Cancer Treatment Center
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Great Falls, Montana, United States, 59405
- Great Falls Clinic
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Great Falls, Montana, United States, 59405
- Benefis Healthcare- Sletten Cancer Institute
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Havre, Montana, United States, 59501
- Northern Montana Hospital
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Helena, Montana, United States, 59601
- Saint Peter's Community Hospital
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Kalispell, Montana, United States, 59901
- Kalispell Regional Medical Center
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Kalispell, Montana, United States, 59901
- Glacier Oncology PLLC
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Kalispell, Montana, United States, 59901
- Kalispell Medical Oncology
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Missoula, Montana, United States, 59802
- Saint Patrick Hospital - Community Hospital
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Missoula, Montana, United States, 59802
- Montana Cancer Specialists
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New Jersey
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Camden, New Jersey, United States, 08103
- Cooper Hospital University Medical Center
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Ohio
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Cincinnati, Ohio, United States, 45236
- The Jewish Hospital
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Cleveland, Ohio, United States, 44106
- Case Western Reserve University
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Cleveland, Ohio, United States, 44109
- MetroHealth Medical Center
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Columbus, Ohio, United States, 43210
- Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
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Dayton, Ohio, United States, 45406
- Good Samaritan Hospital - Dayton
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Dayton, Ohio, United States, 45409
- Miami Valley Hospital
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Dayton, Ohio, United States, 45415
- Samaritan North Health Center
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Dayton, Ohio, United States, 45405
- Grandview Hospital
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Dayton, Ohio, United States, 45420
- Dayton CCOP
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Findlay, Ohio, United States, 45840
- Blanchard Valley Hospital
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Franklin, Ohio, United States, 45005-1066
- Atrium Medical Center-Middletown Regional Hospital
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Greenville, Ohio, United States, 45331
- Wayne Hospital
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Kettering, Ohio, United States, 45429
- Kettering Medical Center
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Troy, Ohio, United States, 45373
- Upper Valley Medical Center
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Wilmington, Ohio, United States, 45177
- Clinton Memorial Hospital
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Xenia, Ohio, United States, 45385
- Greene Memorial Hospital
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Oregon
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Clackamas, Oregon, United States, 97015
- Clackamas Radiation Oncology Center
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Milwaukie, Oregon, United States, 97222
- Providence Milwaukie Hospital
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Newberg, Oregon, United States, 97132
- Providence Newberg Medical Center
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Oregon City, Oregon, United States, 97045
- Providence Willamette Falls Medical Center
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Portland, Oregon, United States, 97213
- Providence Portland Medical Center
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Portland, Oregon, United States, 97225
- Providence Saint Vincent Medical Center
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Portland, Oregon, United States, 97213
- Western Oncology Research Consortium
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Portland, Oregon, United States, 97216
- Adventist Medical Center
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Pennsylvania
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Danville, Pennsylvania, United States, 17822-2001
- Geisinger Medical Center
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Hazleton, Pennsylvania, United States, 18201
- Geisinger Medical Center-Cancer Center Hazelton
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Philadelphia, Pennsylvania, United States, 19111
- Fox Chase Cancer Center
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State College, Pennsylvania, United States, 16801
- Geisinger Medical Group
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Wilkes-Barre, Pennsylvania, United States, 18711
- Geisinger Wyoming Valley
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Washington
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Anacortes, Washington, United States, 98221
- Cancer Care Center at Island Hospital
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Bellingham, Washington, United States, 98225
- PeaceHealth Saint Joseph Medical Center
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Bremerton, Washington, United States, 98310
- Harrison HealthPartners Hematology and Oncology-Bremerton
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Burien, Washington, United States, 98166
- Highline Medical Center-Main Campus
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Issaquah, Washington, United States, 98029
- Swedish Cancer Institute-Issaquah
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Kennewick, Washington, United States, 99336
- Columbia Basin Hematology and Oncology PLLC
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Mount Vernon, Washington, United States, 98274
- Skagit Valley Hospital
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Poulsbo, Washington, United States, 98370
- Harrison HealthPartners Hematology and Oncology-Poulsbo
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Seattle, Washington, United States, 98195
- University of Washington Medical Center
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Seattle, Washington, United States, 98109
- Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
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Seattle, Washington, United States, 98104
- Harborview Medical Center
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Seattle, Washington, United States, 98104
- Minor and James Medical PLLC
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Seattle, Washington, United States, 98112
- Group Health Cooperative-Seattle
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Seattle, Washington, United States, 98122-4307
- Swedish Medical Center-First Hill
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Seattle, Washington, United States, 98122
- The Polyclinic
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Sedro-Woolley, Washington, United States, 98284
- United General Hospital
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Spokane, Washington, United States, 99218
- Evergreen Hematology and Oncology PS
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Spokane, Washington, United States, 99202
- Cancer Care Northwest - Spokane South
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Vancouver, Washington, United States, 98664
- PeaceHealth Southwest Medical Center
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Vancouver, Washington, United States, 98684
- Compass Oncology Vancouver
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Wenatchee, Washington, United States, 98801
- Wenatchee Valley Medical Center
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Wisconsin
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Chippewa Falls, Wisconsin, United States, 54729
- Marshfield Clinic-Chippewa Center
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Eau Claire, Wisconsin, United States, 54701
- Marshfield Clinic Cancer Center at Sacred Heart
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Green Bay, Wisconsin, United States, 54301
- Saint Vincent Hospital
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Green Bay, Wisconsin, United States, 54303
- Green Bay Oncology Limited at Saint Mary's Hospital
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Green Bay, Wisconsin, United States, 54303
- Saint Mary's Hospital
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Green Bay, Wisconsin, United States, 54301-3526
- Green Bay Oncology at Saint Vincent Hospital
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La Crosse, Wisconsin, United States, 54601
- Gundersen Lutheran
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Manitowoc, Wisconsin, United States, 54221
- Holy Family Memorial Hospital
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Marinette, Wisconsin, United States, 54143
- Bay Area Medical Center
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Marshfield, Wisconsin, United States, 54449
- Marshfield Clinic
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Minocqua, Wisconsin, United States, 54548
- Marshfield Clinic-Minocqua Center
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Mukwonago, Wisconsin, United States, 53149
- D N Greenwald Center
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Oconomowoc, Wisconsin, United States, 53066-3896
- Oconomowoc Memorial Hospital-ProHealth Care Inc
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Oconto Falls, Wisconsin, United States, 54154
- Green Bay Oncology - Oconto Falls
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Rhinelander, Wisconsin, United States, 54501
- Marshfield Clinic at James Beck Cancer Center
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Rice Lake, Wisconsin, United States, 54868
- Marshfield Clinic-Rice Lake Center
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Sheboygan, Wisconsin, United States, 53081
- Saint Nicholas Hospital
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Stevens Point, Wisconsin, United States, 54481
- Marshfield Clinic Cancer Care at Saint Michael's Hospital
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Sturgeon Bay, Wisconsin, United States, 54235
- Green Bay Oncology - Sturgeon Bay
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Waukesha, Wisconsin, United States, 53188
- Waukesha Memorial Hospital - ProHealth Care
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Weston, Wisconsin, United States, 54476
- Diagnostic and Treatment Center
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Weston, Wisconsin, United States, 54476
- Marshfield Clinic - Weston Center
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Wisconsin Rapids, Wisconsin, United States, 54494
- Marshfield Clinic - Wisconsin Rapids Center
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Wyoming
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Casper, Wyoming, United States, 82609
- Rocky Mountain Oncology
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Sheridan, Wyoming, United States, 82801
- Welch Cancer Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Histologically confirmed diagnosis of systemic light-chain amyloidosis
- Histologic diagnosis of disease must be confirmed by pathology (positive Congo red stain with green birefringence on polarized light microscopy)
- Genetic testing must be negative for transthyretin mutations associated with hereditary amyloidosis (required in patients who are African-American or who present with peripheral neuropathy as the dominant organ involvement)
Measurable disease, defined by >= 1 of the following:
- Serum M-protein >= 1 g/dL by serum protein electrophoresis (SPEP)
- Difference between involved and uninvolved free light chain be >4.0mg/dL provided the kappa to lambda free light chain (FLC) ratio is abnormal
Symptomatic organ involvement* (heart, kidney, liver/gastrointestinal tract, peripheral nervous system, or soft tissue), defined as any of the following:
- NOTE: *Carpal tunnel syndrome skin purpura or the presence of vascular amyloid on a bone marrow biopsy alone are not sufficient to meet criteria for "symptomatic organ involvement"
- Renal involvement is defined as proteinuria (predominantly albumin) > 0.5 g/day by 24-hour urine collection
- Cardiac involvement is defined as the presence of a mean left ventricular wall thickness of > 12 mm by echocardiogram in the absence of a history of hypertension or valvular heart disease or in the presence of unexplained low voltage (< 0.5 mV) by electrocardiogram
- Hepatic involvement is defined as hepatomegaly or an alkaline phosphatase > 1.5 times upper limit of normal (ULN)
- Peripheral nerve involvement is defined by clinical history or abnormal sensory and/or motor findings on neurologic exam
- Gastrointestinal (GI) involvement is defined as gross GI bleeding or diarrhea (at least 4 stools per day over baseline); a positive GI biopsy is not sufficient to document clinical involvement
- Autonomic nerve involvement is defined as orthostasis, symptoms of nausea or dysgeusia, gastric atony by gastric emptying scan, diarrhea, or constipation
- Soft tissue and lymphatic involvement may be ascertained based on classic physical exam findings (macroglossia, shoulder pad sign, raccoon eyes, carpal tunnel syndrome, synovial enlargement, firm enlarged lymph nodes) or biopsy
- Ineligible for autologous stem cell transplantation with melphalan 200 mg/m^2 or refuses to undergo transplantation
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Amyloid cardiac biomarker stage I or II disease
- The amyloid cardiac staging system is based on NT-proBNP and troponin-T levels. If troponin T (cTnT) is not available at local institution then troponin I (cTnI) may be used. Thresholds for cTnT, cTnI, and NT-proBNP are < 0.035 ug/L, < 0.1 ug/L, and < 332 ng/L, respectively. Stage I patients have both troponin-T (or I) and NT-proBNP below the threshold. Stage II patients have either troponin-T (I) or NT-proBNP above the threshold. Stage III patients have troponin-T (or I) and simultaneous NT-proBNP above the threshold. Stage III patients are further classified as "better risk" if NT-proBNP is over 332 ng/L but less than 6000 ng/L
- Negative pregnancy test
- Fertile patients must use effective contraception
- The absence of supine systolic blood pressure < 100 mmHg and difficult to manage symptomatic orthostatic hypotension
- Absolute neutrophil count (ANC) > 1,500/mm^3
- Platelet count > 140,000/mm^3
- Hemoglobin > 10 g/dL
- Total bilirubin < 2.5 mg/dL
- Alkaline phosphatase < 5 times upper limit of normal (ULN)
- Aspartate aminotransferase (AST) < 3 times ULN
- Creatinine clearance > 30 mL/min
- Bone marrow plasma cells < 30%
Human immunodeficiency virus (HIV)-positivity allowed provided the following criteria are met:
- No history of acquired immunodeficiency syndrome (AIDS)-defining events including history of CD4 cell count < 200/mm^3
- Current CD4 cell count >= 350/mm^3
- Not receiving zidovudine or stavudine
- No secondary amyloidosis
More than 3 weeks since radiotherapy
- Enrollment of subjects who require radiotherapy (which must be localized in field size) should be deferred until the radiotherapy is completed and 3 weeks have elapsed since the last date of therapy
- More than 14 days since prior and no concurrent participation in clinical trials with other investigational agents not included in this trial
Exclusion Criteria:
- Pregnant or nursing
- Clinically overt myeloma (hypercalcemia or lytic bone lesions)
- Prior chemotherapy or radiotherapy for the treatment of myeloma or systemic light-chain amyloidosis
- History of sustained ventricular tachycardias
- Cardiac syncope
- Uncompensated New York Heart Association (NYHA) class III or IV congestive heart failure
- Uncontrolled infection
- Active malignancy within the past 5 years except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or adequately treated stage I cancer currently in complete remission
- Serious medical or psychiatric illness likely to interfere with study participation, including recent myocardial infarction (within the past 6 months) or poorly controlled diabetes mellitus
- Hypersensitivity to bortezomib, boron, or mannitol
- Grade 2 or higher peripheral neuropathy
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: ARM A (Mel-Dex)
Patients receive melphalan 0.22 mg/kg orally (PO) and dexamethasone 40 mg PO on days 1-4 every 4 weeks.
Treatment repeats every 4 weeks for up to 9 courses in the absence of disease progression or unacceptable toxicity.
|
Given PO
Other Names:
Given PO
Other Names:
|
Experimental: ARM B (B-Mel-Dex)
Patients receive melphalan 0.22 mg/kg PO and dexamethasone 40 mg PO on days 1-4 and bortezomib 1.3 mg/m^2 intravenously (IV) on days 1, 4, 8, and 11 every 4 weeks.
Treatment repeats every 4 weeks for 2 cycles.
Patients then receive melphalan PO and dexamethasone PO on days 1-4 and bortezomib IV on days 1, 8, 15, and 22 every 5 weeks.
Treatment repeats every 5 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
|
Given PO
Other Names:
Given IV
Other Names:
Given PO
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Proportion of Patients With Hematologic Overall Response (Partial Response [PR]+ Very Good PR [VGPR]+ Amyloid Complete Response [ACR]+ Stringent Complete Response [sCR]) After 3 Months (3 Cycles) of Therapy
Time Frame: Assessed at 3 months
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sCR: ACR and no clonal cells in bone marrow (BM) ACR: Negative serum/urine immunofixation (IF), <5% plasma cells in BM, and normal serum FLC ratio VGPR: 1. PR and any of the following; 2. serum/urine M-protein detectable by IF but not measurable (NM) on electrophoresis (EP); (3) ≥90% reduction in serum M-component and urine M-protein <100 mg/24 hr if baseline serum measurable; (4) urine M-component <100 mg/24 hr and NM serum M-protein on serum protein EP if baseline urine measurable; (5) ≥90% drop in the difference between involved and uninvolved FLC levels if only FLC measurable PR: (1) ≥50% drop of serum M-protein and 24-hr urinary M-protein drop by ≥90% or to <200 mg/24 hr if baseline serum/urine measurable; or (2) ≥50% drop of serum M-protein if only serum measurable at baseline; or (3) 24-hr urinary M-protein drop by ≥90% or to <200 mg/24 hr if baseline urine measurable; or (4) ≥ 50% drop in the difference between involved and uninvolved FLC if only FLC measu
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Assessed at 3 months
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Collaborators and Investigators
Sponsor
Investigators
- Study Chair: Angela Dispenzieri, M.D., Mayo Clinic
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Metabolic Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Immunoproliferative Disorders
- Paraproteinemias
- Proteostasis Deficiencies
- Neoplasms, Plasma Cell
- Immunoglobulin Light-chain Amyloidosis
- Amyloidosis
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Autonomic Agents
- Peripheral Nervous System Agents
- Anti-Inflammatory Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antiemetics
- Gastrointestinal Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Dexamethasone
- Melphalan
- Bortezomib
Other Study ID Numbers
- NCI-2011-02010 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- U10CA021115 (U.S. NIH Grant/Contract)
- E4A08 (Other Identifier: Eastern Cooperative Oncology Group (ECOG))
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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