Bortezomib and Dexamethasone With or Without Lenalidomide in Treating Patients With Multiple Myeloma Previously Treated With Dexamethasone

Randomized Phase III Trial of Consolidation Therapy With Bortezomib (Velcade®)-Lenalidomide (Revlimid®) -Dexamethasone (VRD) Versus Bortezomib (Velcade®)-Dexamethasone (VD) for Patients With Multiple Myeloma Who Have Completed a Dexamethasone Based Induction Regimen

This randomized phase III trial compares bortezomib, dexamethasone, and lenalidomide with bortezomib and dexamethasone to see how well they work in treating patients with multiple myeloma previously treated with dexamethasone. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Lenalidomide may stimulate the immune system in different ways and stop cancer cells from growing. It is not yet known whether giving bortezomib and dexamethasone is more effective with or without lenalidomide in treating multiple myeloma.

Study Overview

• Status: Terminated
• Conditions: Stage I Multiple Myeloma; Stage II Multiple Myeloma; Stage III Multiple Myeloma
• Intervention / Treatment: Drug: lenalidomide; Drug: dexamethasone; Drug: bortezomib

Detailed Description

PRIMARY OBJECTIVES:

I. To compare the progression-free survival (PFS) for two consolidation regimens: bortezomib, lenalidomide, and dexamethasone (VRD) versus bortezomib and dexamethasone (VD) only.

SECONDARY OBJECTIVES:

I. To determine the incremental ability of VRD versus VD in attaining a complete response or a very good partial response (VGPR) in patients receiving induction therapy with a dexamethasone based induction regimen.

II. To compare the overall survival, measured from the time of study entry.

III. Evaluate response rate and PFS according to cytogenetic category (by gene expression and fluorescence in situ hybridization [FISH]).

IV. To evaluate the toxicity of the two regimens.

V. To compare quality of life (QOL) based on the Functional Assessment of Cancer Therapy (FACT)-Neurotoxicity (Ntx) Trial Outcome Index (TOI) of patients receiving VD to those receiving VRD from registration to 6 months post consolidation treatment.

VI. To examine the impact of differential treatment response (PFS), if observed, on QOL based on the FACT-Ntx TOI up to 12 months post consolidation treatment.

VII. To obtain prospective data on multiple myeloma specific QOL attributes.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients receive bortezomib at 1.3 mg/m2 intravenously (IV) on days 1, 4, 8, and 11, lenalidomide orally (PO) once daily (QD) at 15 mg on days 1-14, and dexamethasone at 40 mg total dose per day PO QD on days 1, 8, and 15. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive bortezomib at 1.3 mg/m2 IV on days 1, 4, 8, and 11 and dexamethasone at 40 mg total dose per day PO QD on days 1, 8, and 15. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 3 years, and then every 12 months for 5 years.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 3

Contacts and Locations

Study Locations

• South Africa
  • Pretoria, South Africa, 0002
    • University of Pretoria
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic in Arizona
  • California
    • Fairfield, California, United States, 94533
      • Northbay Cancer Center
    • San Diego, California, United States, 92120
      • Kaiser Permanente
    • Stanford, California, United States, 94305
      • Stanford University Hospitals and Clinics
  • Colorado
    • Aurora, Colorado, United States, 80012
      • The Medical Center of Aurora
    • Boulder, Colorado, United States, 80301
      • Boulder Community Hospital
    • Colorado Springs, Colorado, United States, 80907
      • Penrose-Saint Francis Healthcare
    • Denver, Colorado, United States, 80210
      • Porter Adventist Hospital
    • Denver, Colorado, United States, 80218
      • Presbyterian - Saint Lukes Medical Center - Health One
    • Denver, Colorado, United States, 80220
      • Rose Medical Center
    • Denver, Colorado, United States, 80218
      • Exempla Saint Joseph Hospital
    • Denver, Colorado, United States, 80224-2522
      • Colorado Cancer Research Program CCOP
    • Englewood, Colorado, United States, 80113
      • Swedish Medical Center
    • Grand Junction, Colorado, United States, 81502
      • Saint Mary's Hospital and Regional Medical Center
    • Greeley, Colorado, United States, 80631
      • North Colorado Medical Center
    • Lakewood, Colorado, United States, 80228
      • Saint Anthony Hospital
    • Lone Tree, Colorado, United States, 80124
      • Sky Ridge Medical Center
    • Longmont, Colorado, United States, 80501
      • Longmont United Hospital
    • Loveland, Colorado, United States, 80539
      • McKee Medical Center
    • Pueblo, Colorado, United States, 81004
      • Saint Mary Corwin Medical Center
    • Thornton, Colorado, United States, 80229
      • North Suburban Medical Center
    • Wheat Ridge, Colorado, United States, 80033
      • Exempla Lutheran Medical Center
  • Delaware
    • Lewes, Delaware, United States, 19958
      • Beebe Medical Center
    • Newark, Delaware, United States, 19718
      • Christiana Care Health System-Christiana Hospital
  • Florida
    • Jacksonville, Florida, United States, 32224-9980
      • Mayo Clinic in Florida
  • Georgia
    • Columbus, Georgia, United States, 31904
      • John B Amos Cancer Center
    • Rome, Georgia, United States, 30165
      • Harbin Clinic Medical Oncology and Clinical Research
  • Illinois
    • Alton, Illinois, United States, 62002
      • Saint Anthony's Health
    • Bloomington, Illinois, United States, 61701
      • Saint Joseph Medical Center
    • Canton, Illinois, United States, 61520
      • Graham Hospital Association
    • Carthage, Illinois, United States, 62321
      • Memorial Hospital
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital
    • Elk Grove Village, Illinois, United States, 60007
      • Alexian Brothers Medical and Cancer Center
    • Eureka, Illinois, United States, 61530
      • Eureka Hospital
    • Evanston, Illinois, United States, 60202
      • Saint Francis Hospital
    • Galesburg, Illinois, United States, 61401
      • Western Illinois Cancer Treatment Center
    • Galesburg, Illinois, United States, 61401
      • Galesburg Cottage Hospital
    • Galesburg, Illinois, United States, 61401
      • Illinois CancerCare Galesburg
    • Havana, Illinois, United States, 62644
      • Mason District Hospital
    • Hopedale, Illinois, United States, 61747
      • Hopedale Medical Complex - Hospital
    • Joliet, Illinois, United States, 60435
      • Joliet Oncology-Hematology Associates Limited
    • Macomb, Illinois, United States, 61455
      • Mcdonough District Hospital
    • Moline, Illinois, United States, 61265
      • Garneau, Stewart C MD (UIA Investigator)
    • Moline, Illinois, United States, 61265
      • Porubcin, Michael MD (UIA Investigator)
    • Moline, Illinois, United States, 61265
      • Sharis, Christine M MD (UIA Investigator)
    • Moline, Illinois, United States, 61265
      • Stoffel, Thomas J MD (UIA Investigator)
    • Mount Vernon, Illinois, United States, 62864
      • Good Samaritan Regional Health Center
    • Normal, Illinois, United States, 61761
      • Community Cancer Center Foundation
    • Normal, Illinois, United States, 61761
      • Bromenn Regional Medical Center
    • Ottawa, Illinois, United States, 61350
      • Illinois CancerCare-Ottawa Clinic
    • Ottawa, Illinois, United States, 61350
      • Ottawa Regional Hospital and Healthcare Center
    • Pekin, Illinois, United States, 61554
      • Pekin Cancer Treatment Center
    • Pekin, Illinois, United States, 61554
      • Pekin Hospital
    • Peoria, Illinois, United States, 61637
      • OSF Saint Francis Medical Center
    • Peoria, Illinois, United States, 61614
      • Proctor Hospital
    • Peoria, Illinois, United States, 61603
      • Methodist Medical Center of Illinois
    • Peoria, Illinois, United States, 61615
      • Illinois Oncology Research Association CCOP
    • Peru, Illinois, United States, 61354
      • Valley Radiation Oncology
    • Peru, Illinois, United States, 61354
      • Illinois Valley Hospital
    • Princeton, Illinois, United States, 61356
      • Perry Memorial Hospital
    • Spring Valley, Illinois, United States, 61362
      • Saint Margaret's Hospital
    • Springfield, Illinois, United States, 62781-0001
      • Memorial Medical Center
    • Urbana, Illinois, United States, 61801
      • Carle Clinic-Urbana Main
  • Indiana
    • Beech Grove, Indiana, United States, 46107
      • Saint Francis Hospital and Health Centers
    • Richmond, Indiana, United States, 47374
      • Reid Hospital and Health Care Services
  • Iowa
    • Ames, Iowa, United States, 50010
      • McFarland Clinic PC-William R Bliss Cancer Center
    • Bettendorf, Iowa, United States, 52722
      • Constantinou, Costas L MD (UIA Investigator)
    • Des Moines, Iowa, United States, 50309
      • Iowa Methodist Medical Center
    • Des Moines, Iowa, United States, 50314
      • Mercy Medical Center - Des Moines
    • Des Moines, Iowa, United States, 50309
      • Medical Oncology and Hematology Associates-Des Moines
    • Des Moines, Iowa, United States, 50316
      • Iowa Lutheran Hospital
    • Des Moines, Iowa, United States, 50314
      • Medical Oncology and Hematology Associates-Laurel
    • Des Moines, Iowa, United States, 50307
      • Mercy Capitol
    • Des Moines, Iowa, United States, 50309
      • Iowa Oncology Research Association CCOP
    • Sioux City, Iowa, United States, 51104
      • Saint Luke's Regional Medical Center
    • Sioux City, Iowa, United States, 51101
      • Siouxland Hematology Oncology Associates
    • Sioux City, Iowa, United States, 51104
      • Mercy Medical Center-Sioux City
    • Waterloo, Iowa, United States, 50702
      • Covenant Medical Center
  • Kansas
    • Lawrence, Kansas, United States, 66044
      • Lawrence Memorial Hospital
    • Wichita, Kansas, United States, 67214
      • Wesley Medical Center
  • Kentucky
    • Louisville, Kentucky, United States, 40215
      • Doctors Carrol, Sheth, Raghavan
  • Maryland
    • Elkton MD, Maryland, United States, 21921
      • Union Hospital of Cecil County
  • Michigan
    • Adrian, Michigan, United States, 49221
      • Bixby Medical Center
    • Adrian, Michigan, United States, 49221
      • Hickman Cancer Center
    • Ann Arbor, Michigan, United States, 48106-0995
      • Saint Joseph Mercy Hospital
    • Ann Arbor, Michigan, United States, 48106
      • Michigan Cancer Research Consortium Community Clinical Oncology Program
    • Dearborn, Michigan, United States, 48124
      • Oakwood Hospital
    • Detroit, Michigan, United States, 48236
      • Saint John Hospital and Medical Center
    • Escanaba, Michigan, United States, 49431
      • Green Bay Oncology - Escanaba
    • Flint, Michigan, United States, 48502
      • Hurley Medical Center
    • Flint, Michigan, United States, 48532
      • Genesys Regional Medical Center-West Flint Campus
    • Iron Mountain, Michigan, United States, 49801
      • Green Bay Oncology - Iron Mountain
    • Jackson, Michigan, United States, 49201
      • Allegiance Health
    • Lansing, Michigan, United States, 48912
      • Sparrow Hospital
    • Livonia, Michigan, United States, 48154
      • Saint Mary Mercy Hospital
    • Monroe, Michigan, United States, 48162
      • Mercy Memorial Hospital
    • Monroe, Michigan, United States, 48162
      • Community Cancer Center of Monroe
    • Pontiac, Michigan, United States, 48341-2985
      • Saint Joseph Mercy Oakland
    • Port Huron, Michigan, United States, 48060
      • Saint Joseph Mercy Port Huron
    • Saginaw, Michigan, United States, 48601
      • Saint Mary's of Michigan
    • Warren, Michigan, United States, 48093
      • Saint John Macomb-Oakland Hospital
  • Minnesota
    • Bemidji, Minnesota, United States, 56601
      • Sanford Clinic North-Bemidgi
    • Burnsville, Minnesota, United States, 55337
      • Fairview Ridges Hospital
    • Coon Rapids, Minnesota, United States, 55433
      • Mercy Hospital
    • Duluth, Minnesota, United States, 55805
      • Essentia Health Saint Mary's Medical Center
    • Duluth, Minnesota, United States, 55805
      • Miller-Dwan Hospital
    • Duluth, Minnesota, United States, 55805
      • Essentia Health Duluth Clinic CCOP
    • Edina, Minnesota, United States, 55435
      • Fairview-Southdale Hospital
    • Fridley, Minnesota, United States, 55432
      • Unity Hospital
    • Hutchinson, Minnesota, United States, 55350
      • Hutchinson Area Health Care
    • Litchfield, Minnesota, United States, 55355
      • Meeker County Memorial Hospital
    • Maplewood, Minnesota, United States, 55109
      • Saint John's Hospital - Healtheast
    • Maplewood, Minnesota, United States, 55109
      • Minnesota Oncology Hematology PA-Maplewood
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center
    • Minneapolis, Minnesota, United States, 55407
      • Abbott-Northwestern Hospital
    • Minneapolis, Minnesota, United States, 55407
      • Virginia Piper Cancer Institute
    • Robbinsdale, Minnesota, United States, 55422
      • North Memorial Medical Health Center
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
    • Saint Louis Park, Minnesota, United States, 55416
      • Park Nicollet Clinic - Saint Louis Park
    • Saint Louis Park, Minnesota, United States, 55416
      • Metro-Minnesota CCOP
    • Saint Paul, Minnesota, United States, 55101
      • Regions Hospital
    • Saint Paul, Minnesota, United States, 55102
      • United Hospital
    • Saint Paul, Minnesota, United States, 55102
      • Saint Joseph's Hospital - Healtheast
    • Shakopee, Minnesota, United States, 55379
      • Saint Francis Regional Medical Center
    • Waconia, Minnesota, United States, 55387
      • Ridgeview Medical Center
    • Woodbury, Minnesota, United States, 55125
      • Woodwinds Health Campus
    • Woodbury, Minnesota, United States, 55125
      • Minnesota Oncology and Hematology PA-Woodbury
  • Missouri
    • Cape Girardeau, Missouri, United States, 63703
      • Saint Francis Medical Center
    • Cape Girardeau, Missouri, United States, 63701
      • Southeast Missouri Hospital
    • Columbia, Missouri, United States, 65212
      • University of Missouri - Ellis Fischel
    • Jefferson City, Missouri, United States, 65101
      • Capital Regional Medical Center
    • Saint Louis, Missouri, United States, 63131
      • Missouri Baptist Medical Center
    • Saint Louis, Missouri, United States, 63109
      • Saint Louis Cancer and Breast Institute-South City
    • Saint Louis, Missouri, United States, 63141
      • Saint John's Mercy Medical Center
    • Saint Louis, Missouri, United States, 63141
      • Saint Louis-Cape Girardeau CCOP
    • Saint Louis, Missouri, United States, 63141
      • Center for Cancer Care and Research
    • Springfield, Missouri, United States, 65804
      • Mercy Hospital Springfield
    • Springfield, Missouri, United States, 65802
      • Ozark Health Ventures LLC dba Cancer Research for The Ozarks Springfield
  • Montana
    • Billings, Montana, United States, 59101
      • Saint Vincent Healthcare
    • Billings, Montana, United States, 59101
      • Northern Rockies Radiation Oncology Center
    • Billings, Montana, United States, 59101
      • Montana Cancer Consortium CCOP
    • Billings, Montana, United States, 59102
      • Hematology-Oncology Centers of the Northern Rockies PC
    • Billings, Montana, United States, 59107-7000
      • Billings Clinic
    • Bozeman, Montana, United States, 59715
      • Bozeman Deaconess Hospital
    • Bozeman, Montana, United States, 59715
      • Bozeman Deaconess Cancer Center
    • Butte, Montana, United States, 59701
      • Saint James Community Hospital and Cancer Treatment Center
    • Great Falls, Montana, United States, 59405
      • Great Falls Clinic
    • Great Falls, Montana, United States, 59405
      • Berdeaux, Donald MD (UIA Investigator)
    • Havre, Montana, United States, 59501
      • Northern Montana Hospital
    • Helena, Montana, United States, 59601
      • Saint Peter's Community Hospital
    • Kalispell, Montana, United States, 59901
      • Kalispell Regional Medical Center
    • Kalispell, Montana, United States, 59901
      • Glacier Oncology PLLC
    • Kalispell, Montana, United States, 59901
      • Kalispell Medical Oncology
    • Missoula, Montana, United States, 59802
      • Saint Patrick Hospital - Community Hospital
    • Missoula, Montana, United States, 59804
      • Guardian Oncology and Center for Wellness
    • Missoula, Montana, United States, 59801
      • Community Medical Hospital
    • Missoula, Montana, United States, 59802
      • Montana Cancer Specialists
  • Nebraska
    • Kearney, Nebraska, United States, 68847
      • Good Samaritan Hospital
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • University Medical Center of Southern Nevada
    • Las Vegas, Nevada, United States, 89106
      • Nevada Cancer Research Foundation CCOP
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cooper Hospital University Medical Center
    • East Orange, New Jersey, United States, 07018-1095
      • Veterans Adminstration New Jersey Health Care System
    • Mount Holly, New Jersey, United States, 08060
      • Fox Chase Cancer Center at Virtua Memorial Hospital of Burlington County
    • Voorhees, New Jersey, United States, 08043
      • Virtua West Jersey Hospital Voorhees
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • University of New Mexico Cancer Center
  • New York
    • Bronx, New York, United States, 10467-2490
      • Montefiore Medical Center
    • Brooklyn, New York, United States, 11203
      • Kings County Hospital
    • Brooklyn, New York, United States, 11203
      • University Hospital of Brooklyn
    • Brooklyn, New York, United States, 11203
      • State University of New York Downstate Medical Center
    • Cooperstown, New York, United States, 13326
      • Mary Imogene Bassett Hospital
    • Glens Falls, New York, United States, 12801
      • Adirondack Cancer Center
    • Middletown, New York, United States, 10940
      • Orange Regional Medical Center
  • North Dakota
    • Fargo, North Dakota, United States, 58122
      • Sanford Clinic North-Fargo
    • Fargo, North Dakota, United States, 58122
      • Sanford Medical Center-Fargo
  • Ohio
    • Bellefontaine, Ohio, United States, 43311
      • Mary Rutan Hospital
    • Bowling Green, Ohio, United States, 43402
      • Toledo Clinic Cancer Centers-Bowling Green
    • Canton, Ohio, United States, 44708
      • Mercy Medical Center
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University
    • Columbus, Ohio, United States, 43214
      • Riverside Methodist Hospital
    • Columbus, Ohio, United States, 43228
      • Doctors Hospital
    • Columbus, Ohio, United States, 43215
      • Grant Medical Center
    • Columbus, Ohio, United States, 43222
      • Mount Carmel Health Center West
    • Dayton, Ohio, United States, 45406
      • Good Samaritan Hospital - Dayton
    • Dayton, Ohio, United States, 45409
      • Miami Valley Hospital
    • Dayton, Ohio, United States, 45415
      • Samaritan North Health Center
    • Dayton, Ohio, United States, 45405
      • Grandview Hospital
    • Dayton, Ohio, United States, 45420
      • Dayton CCOP
    • Dayton, Ohio, United States, 45428
      • Veteran Affairs Medical Center
    • Delaware, Ohio, United States, 43015
      • Grady Memorial Hospital
    • Elyria, Ohio, United States, 44035
      • Hematology Oncology Center Incorporated
    • Findlay, Ohio, United States, 45840
      • Blanchard Valley Hospital
    • Franklin, Ohio, United States, 45005-1066
      • Atrium Medical Center-Middletown Regional Hospital
    • Fremont, Ohio, United States, 43420
      • Fremont Memorial Hospital
    • Greenville, Ohio, United States, 45331
      • Wayne Hospital
    • Kettering, Ohio, United States, 45429
      • Kettering Medical Center
    • Lancaster, Ohio, United States, 43130
      • Fairfield Medical Center
    • Lima, Ohio, United States, 45804
      • Lima Memorial Hospital
    • Marietta, Ohio, United States, 45750
      • Marietta Memorial Hospital
    • Maumee, Ohio, United States, 43537
      • Toledo Clinic Cancer Centers-Maumee
    • Maumee, Ohio, United States, 43537
      • Toledo Radiation Oncology at Northwest Ohio Onocolgy Center
    • Maumee, Ohio, United States, 43537
      • Saint Luke's Hospital
    • Newark, Ohio, United States, 43055
      • Licking Memorial Hospital
    • Norwalk, Ohio, United States, 44857
      • Fisher-Titus Medical Center
    • Oregon, Ohio, United States, 43616
      • Saint Charles Hospital
    • Oregon, Ohio, United States, 43616
      • Toledo Clinic Cancer Centers-Oregon
    • Sandusky, Ohio, United States, 44870
      • North Coast Cancer Care
    • Sandusky, Ohio, United States, 44870
      • Firelands Regional Medical Center
    • Sylvania, Ohio, United States, 43560
      • Flower Hospital
    • Tiffin, Ohio, United States, 44883
      • Mercy Hospital of Tiffin
    • Toledo, Ohio, United States, 43608
      • Saint Vincent Mercy Medical Center
    • Toledo, Ohio, United States, 43623
      • Toledo Clinic Cancer Centers-Toledo
    • Toledo, Ohio, United States, 43614
      • University of Toledo
    • Toledo, Ohio, United States, 43617
      • Toledo Community Hospital Oncology Program CCOP
    • Toledo, Ohio, United States, 43606
      • The Toledo Hospital/Toledo Children's Hospital
    • Toledo, Ohio, United States, 43623
      • Mercy Saint Anne Hospital
    • Troy, Ohio, United States, 45373
      • Upper Valley Medical Center
    • Wauseon, Ohio, United States, 43567
      • Fulton County Health Center
    • Westerville, Ohio, United States, 43081
      • Saint Ann's Hospital
    • Wilmington, Ohio, United States, 45177
      • Clinton Memorial Hospital
    • Xenia, Ohio, United States, 45385
      • Greene Memorial Hospital
    • Zanesville, Ohio, United States, 43701
      • Genesis HealthCare System
  • Oregon
    • Portland, Oregon, United States, 97216
      • Adventist Medical Center
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Abington Memorial Hospital
    • Bryn Mawr, Pennsylvania, United States, 19010
      • Bryn Mawr Hospital
    • Danville, Pennsylvania, United States, 17822-2001
      • Geisinger Medical Center
    • Doylestown, Pennsylvania, United States, 18901
      • Doylestown Hospital
    • Hazleton, Pennsylvania, United States, 18201
      • Geisinger Medical Center-Cancer Center Hazleton
    • Lancaster, Pennsylvania, United States, 17604
      • Lancaster General Hospital
    • Paoli, Pennsylvania, United States, 19301
      • Paoli Memorial Hospital
    • Pottstown, Pennsylvania, United States, 19464
      • Pottstown Memorial Medical Center
    • State College, Pennsylvania, United States, 16801
      • Geisinger Medical Group
    • West Reading, Pennsylvania, United States, 19611
      • Reading Hospital
    • Wilkes-Barre, Pennsylvania, United States, 18711
      • Geisinger Wyoming Valley
    • Wynnewood, Pennsylvania, United States, 19096
      • Lankenau Hospital
    • Wynnewood, Pennsylvania, United States, 19096
      • Mainline Health CCOP
  • South Carolina
    • Florence, South Carolina, United States, 29506
      • McLeod Regional Medical Center
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Rapid City Regional Hospital
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • University of Tennessee - Knoxville
  • Virginia
    • Fredericksburg, Virginia, United States, 22401
      • Fredericksburg Oncology Inc
  • Washington
    • Bellingham, Washington, United States, 98225
      • PeaceHealth Saint Joseph Medical Center
    • Bremerton, Washington, United States, 98310
      • Harrison HealthPartners Hematology and Oncology-Bremerton
    • Kennewick, Washington, United States, 99336
      • Columbia Basin Hematology and Oncology PLLC
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
    • Seattle, Washington, United States, 98104
      • Harborview Medical Center
    • Seattle, Washington, United States, 98104
      • Minor and James Medical PLLC
    • Seattle, Washington, United States, 98122-4307
      • Swedish Medical Center-First Hill
    • Seattle, Washington, United States, 98122
      • The Polyclinic
    • Wenatchee, Washington, United States, 98801
      • Wenatchee Valley Medical Center
  • West Virginia
    • Wheeling, West Virginia, United States, 26003
      • Wheeling Hospital
    • Wheeling, West Virginia, United States, 26003
      • The Schiffler Cancer Center of Wheeling Hospital
  • Wisconsin
    • Chippewa Falls, Wisconsin, United States, 54729
      • Marshfield Clinic-Chippewa Center
    • Eau Claire, Wisconsin, United States, 54701
      • Marshfield Clinic Cancer Center at Sacred Heart
    • Eau Claire, Wisconsin, United States, 54701
      • Sacred Heart Hospital
    • Green Bay, Wisconsin, United States, 54301
      • Saint Vincent Hospital
    • Green Bay, Wisconsin, United States, 54303
      • Green Bay Oncology Limited at Saint Mary's Hospital
    • Green Bay, Wisconsin, United States, 54303
      • Saint Mary's Hospital
    • Green Bay, Wisconsin, United States, 54301-3526
      • Green Bay Oncology at Saint Vincent Hospital
    • Johnson Creek, Wisconsin, United States, 53038
      • UW Cancer Center Johnson Creek
    • La Crosse, Wisconsin, United States, 54601
      • Mayo Clinic Health System-Franciscan Healthcare
    • La Crosse, Wisconsin, United States, 54601
      • Gundersen Lutheran
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Hospital and Clinics
    • Marinette, Wisconsin, United States, 54143
      • Bay Area Medical Center
    • Marshfield, Wisconsin, United States, 54449
      • Marshfield Clinic
    • Marshfield, Wisconsin, United States, 54449
      • Saint Joseph's Hospital
    • Minocqua, Wisconsin, United States, 54548
      • Marshfield Clinic-Minocqua Center
    • Oconto Falls, Wisconsin, United States, 54154
      • Green Bay Oncology - Oconto Falls
    • Rhinelander, Wisconsin, United States, 54501
      • Marshfield Clinic at James Beck Cancer Center
    • Rice Lake, Wisconsin, United States, 54868
      • Marshfield Clinic-Rice Lake Center
    • Stevens Point, Wisconsin, United States, 54481
      • Saint Michael's Hospital
    • Sturgeon Bay, Wisconsin, United States, 54235
      • Green Bay Oncology - Sturgeon Bay
    • Wausau, Wisconsin, United States, 54401
      • Marshfield Clinic-Wausau Center
    • Weston, Wisconsin, United States, 54476
      • Marshfield Clinic - Weston Center
    • Wisconsin Rapids, Wisconsin, United States, 54494
      • Marshfield Clinic - Wisconsin Rapids Center
  • Wyoming
    • Sheridan, Wyoming, United States, 82801
      • Welch Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Symptomatic multiple myeloma, that was symptomatic at time of initial diagnosis, but may be asymptomatic at the time of registration based on induction therapy
• For the original diagnosis of myeloma, patients must have met the following criteria at one point in their disease course: bone marrow plasmacytosis (>10% plasma cells or sheets of plasma cells) or a biopsy proven plasmacytoma, and evidence of end-organ damage due to multiple myeloma including anemia, hypercalcemia, bone disease (lytic bone lesions or pathologic fractures) or renal dysfunction.
• Patients may have prior exposure to bortezomib
• Patients must have received a minimum of 1 cycle, maximum of 6 cycles, of a dexamethasone-based regimen; patient must not have experienced progressive disease on such therapy
• The following induction regimens were considered adequate for enrollment: dexamethasone alone; vincristine, doxorubicin and dexamethasone; thalidomide and dexamethasone; lenalidomide and dexamethasone; liposomal doxorubicin and dexamethasone; the combination of any of the above agents and dexamethasone; or cyclophosphamide, lenalidomide and dexamethasone
• Patients must have received the minimum cumulative dose of dexamethasone of 160 mg (sum of induction treatment) with no maximum dose specified
• Patients must have been offered and refused front-line stem cell transplant OR not have been eligible for front-line stem cell transplant.
• Bone marrow aspiration and/or biopsy must be obtained =< 28 days prior to randomization

• All tests below must be performed =< 28 days prior to randomization:

  • Kappa free light chain mg/dL
  • Lambda free light chain mg/dL
  • Serum M-protein by serum protein electrophoresis (SPEP)
  • Urine M-protein light chain excretion by urine protein electrophoresis (UPEP)
• Adequate laboratory levels within 7 days prior to randomization: hemoglobin > 7 g/dL, platelet count > 75,000 cells/mm^3, absolute neutrophil count > 1000 cells/mm^3, creatinine < 2.5 mg/dL, creatinine clearance (measured or calculated) >= 60 mL/min, direct bilirubin =< 1.5 mg/dL, serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) and serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 2.5 times the upper limit of normal
• Patients may be receiving bisphosphonates or erythropoietin growth factors (erythropoietic agents) for multiple myeloma
• Prior palliative and/or localized radiation therapy is permitted, provided at least 14 days have passed from date of last radiation therapy to date of randomization
• Patients must be willing and able to take prophylaxis with either aspirin at 325 mg/day or alternative prophylaxis with either low molecular weight heparin or coumadin (patients with prior deep vein thrombosis [DVT] are eligible provided they remain on the anticoagulation regimen that was prescribed for treatment of the DVT throughout the protocol therapy)
• Patients must be competent to understand the study as explained in the consent form
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
• Sexually active males must be willing to use a condom (even if they have undergone a prior vasectomy) while having intercourse with any woman, while taking lenalidomide, and for 4 weeks after stopping treatment
• Patients with a history of prior malignancy are eligible provided there is no active malignancy and a low expectation of recurrence within 6 months
• Age >=18 years

Exclusion Criteria:

• More than 8 weeks from the last day of last cycle of induction treatment
• Active, uncontrolled seizure disorder; seizures in the last 6 months
• Uncontrolled inter-current illness that would limit compliance with the study including uncontrolled hypertension, symptomatic congestive heart failure, unstable angina, uncontrolled cardiac arrhythmia, uncontrolled psychiatric illness or social situation, prior history of Stevens Johnson syndrome
• Grade 2 or higher peripheral neuropathy by Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
• Active, uncontrolled infection
• Smoldering myeloma or monoclonal gammopathy of undetermined significance
• Pregnant or nursing women were not eligible. Women of child-bearing potential unwilling to use a dual method of contraception and men who were unwilling to use a condom were not eligible

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A (VRD); Patients were given consolidation therapy for 8 cycles (1 cycle = 21 days) with the combination bortezomib, dexamethasone and lenalidomide. Patients received each cycle: the standard dose of bortezomib (1.3 mg/m2) on days 1, 4, 8 and 11; fixed dose of lenalidomide at 15 mg orally on days 1-14; and 3 days of dexamethasone at 40 mg total dose per day given on days 1, 8 and 15. Aspirin 325 mg/day orally on days 1-21 of each cycle was required unless the patient was treated with alternate prophylaxis of either low molecular weight heparin or coumadin.	Drug: lenalidomide; Given PO; Other Names: CC-5013; CDC-501; Revlimid® (formerly Revimid®); Drug: dexamethasone; Given PO; Other Names: Decadron; DXM; Dexameth; Dexone; Hexadrol; Drug: bortezomib; Given IV; Other Names: PS-341; VELCADE; LDP-341; MLN-341
Active Comparator: Arm B (VD); Patients were given consolidation therapy for 8 cycles (1 cycle = 21 days) with the combination bortezomib plus dexamethasone. Patients received each cycle: the standard dose of bortezomib (1.3 mg/m2) on days 1, 4, 8 and 11 and 3 days of dexamethasone at 40 mg total dose per day given on days 1, 8 and 15.	Drug: dexamethasone; Given PO; Other Names: Decadron; DXM; Dexameth; Dexone; Hexadrol; Drug: bortezomib; Given IV; Other Names: PS-341; VELCADE; LDP-341; MLN-341

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS)	Progression-free survival was defined as the time from randomization to the earliest documentation of disease progression (PD) or death. If a patient died without evidence of PD, the patient was considered an event if death occurred within 3 months of the last disease assessment. Patients who died outside of the specified interval or patients who were alive without evidence of PD were censored at the date of last disease assessment. The PFS results are based on data as of August 2012, while overall survival (OS) was updated in April 2014. Given the early termination and limited sample size, data management efforts to update PFS were not pursued.	Assessed every 3 months if patient is < 2 years from study entry, every 6 months if patient is 2-5 years from study entry, every 12 months if patient is 6-10 years from study entry, up to 10 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Rates (Complete Response [CR] or Very Good Partial Response [VGPR])	CR: Patients with complete disappearance of an M-protein and no evidence of myeloma in the bone marrow are considered to have CR. To be considered CR, patients must meet all of the following criteria: Negative immunofixation on the serum and urine at two consecutive times; Disappearance of any soft tissue plasmacytomas; ≤5% plasma cells in bone marrow; If serum and urine M protein are unmeasurable and the immunoglobulin free light chain (FLC) parameter is being used, patients must have a normal ratio of 0.26-1.65 at two consecutive times VGPR: Serum and urine M-component detectable by immunofixation but not on electrophoresis OR; >=90% reduction in serum M-component plus urine M-component <100 mg per 24 hours (by SPEP and UPEP); If the serum and urine M protein are unmeasurable and the immunoglobulin FLC parameter is being used, a >90% decrease in the difference between involved and uninvolved FLC levels is required in place of the M protein criteria	Assessed at the end of each cycle, every 3 months if patient is < 2 years from study entry, every 6 months if patient is 2-5 years from study entry, every 12 months if patient is 6-10 years from study entry, up to 10 years
Overall Survival (OS)	Overall survival is defined as the time from randomization to death or date of last known alive. The OS results are based on data as of April 2014.	Assessed every 3 months if patient is < 2 years from study entry, every 6 months if patient is 2-5 years from study entry, every 12 months if patient is 6-10 years from study entry, up to 10 years
Change in Quality of Life (QOL) From Baseline to 6 Months Post Consolidation as Assessed by the Functional Assessment of Cancer Therapy-Neurotoxicity Trial Outcome Index (FACT-Ntx TOI)	The combined score on the FACT-Ntx TOI is of interest. The FACT-Ntx TOI has 25 items and the score ranges from 0 (worst possible quality of life) -100 (best possible quality of life). The primary QOL endpoint is defined as the change in the FACT-Ntx TOI score from registration to 6 months post consolidation treatment.	Baseline and 6 months post consolidation treatment

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Study Chair: Rafael Fonseca, M.D., Mayo Clinic

Publications and helpful links

General Publications

• Fonseca R, Rajkumar SV. Consolidation therapy with bortezomib/lenalidomide/ dexamethasone versus bortezomib/dexamethasone after a dexamethasone-based induction regimen in patients with multiple myeloma: a randomized phase III trial. Clin Lymphoma Myeloma. 2008 Oct;8(5):315-7. doi: 10.3816/CLM.2008.n.046.

Study record dates

Study Major Dates

• Study Start: September 1, 2007
• Primary Completion (Actual): August 1, 2012
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: August 28, 2007
• First Submitted That Met QC Criteria: August 28, 2007
• First Posted (Estimate): August 29, 2007

Study Record Updates

• Last Update Posted (Estimate): June 26, 2015
• Last Update Submitted That Met QC Criteria: June 23, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Keywords: Quality of life; Proteasome inhibitor; Consolidation therapy; First-line therapy; Thalidomide analogue
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Dexamethasone; Lenalidomide; Bortezomib
• Other Study ID Numbers: NCI-2009-00521 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U10CA180820 (U.S. NIH Grant/Contract); U10CA021115 (U.S. NIH Grant/Contract); E1A05 (Other Identifier: Eastern Cooperative Oncology Group (ECOG))