Multiple MyelomaPhase 3UPFRONTNCT00507416
Velcade,Thalidomide, and Dexamethasone Versus Velcade and Dexamethasone Versus Velcade, Melphalan, and Prednisone
A Phase 3 study testing Bortezomib, Dexamethasone and Melphalan in people with Multiple Myeloma, run by Millennium Pharmaceuticals, Inc. at 235 sites in 2 countries.
Trial summary
This is a randomized, open label, multicenter clinical trial to compare the efficacy and safety of Velcade (bortezomib) and dexamethasone versus Velcade, thalidomide, and dexamethasone versus Velcade, melphalan, and prednisone in patients with previously untreated multiple myeloma not considered candidates for… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- Bortezomib, Dexamethasone and Melphalan
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 502 participants
- Where
- 235 sitesin 2 countries
- Study dates
- Jun 2007to Mar 2013
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female 18 years of age or older
- Not a candidate for high-dose chemotherapy and stem cell transplantation (HDT/SCT) due to age, presence of important comorbid condition(s) likely to have a negative impact on tolerability of HDT-SCT, or subject preference.
- A Karnofsky Performance Status score of ≥50%
- Symptomatic multiple myeloma or asymptomatic multiple myeloma with related organ or tissue damage.
- Asymptomatic multiple myeloma-related organ or tissue damage can include presence of an asymptomatic lytic bone lesion or plasmacytoma, the presence of anemia (hemoglobin <10 g/dL), renal function impairment (serum creatinine > upper limit of normal [ULN]) or hypercalcemia (serum calcium >ULN).
- Must have measurable disease requiring systemic therapy. Measurable disease is defined by at least 1 of the following criteria:
Show all 9Show fewer
- Quantifiable serum M-protein value (>1 g/dL of immunoglobulin (Ig)G or IgM M-protein, >0.5g/dL of IgA M-protein, >0.5 g/dL of IgD M-protein)
- Urine light-chain excretion ≥200 mg/24 hours
- Voluntary written informed consent must be given before performance of any study related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the participant at any time without prejudice to future medical care.
Who cannot join
- Diagnosis of smoldering multiple myeloma or monoclonal gammopathy of undetermined significance (MGUS). Smoldering multiple myeloma is defined as asymptomatic multiple myeloma with absence of lytic bone lesions. MGUS is defined by presence of serum monoclonal protein <3 g/dL; absence of lytic bone lesions, anemia, hypercalcemia, and renal insufficiency related to the monoclonal protein; and (if determined) proportion of plasma cells in the bone marrow of 10% or less.
- Diagnosis of Waldenström's disease or other conditions in which immunoglobulin M (IgM) M-protein is present in the absence of a clonal plasma cell infiltration or lytic bone lesions.
- Previously or currently treated with any systemic therapy for multiple myeloma. Prior treatment of hypercalcemia or spinal cord compression with corticosteroids or radiation therapy, respectively, does not disqualify the subject (the dose of corticosteroids should not exceed the equivalent of 160 mg of dexamethasone in 2-week period).
- Radiation therapy within 2 weeks before randomization. Enrollment of patients who require concurrent radiotherapy (which must be localized in its field size) should be deferred until the radiotherapy is completed and 2 weeks have elapsed since the last date of therapy.
- Major surgery within 30 days before randomization (Kyphoplasty is not considered major surgery)
- History of allergy to any of the study medications, their analogues, or excipients in the various formulations
Show all 17Show fewer
- ≥Grade 2 peripheral neuropathy on clinical examination within 21 days before enrollment.
- Any of the following clinical laboratory values within 21 days prior to enrollment:
- Absolute neutrophil count (ANC) <1000 cells/mm^3
- Platelets <100,000 × 10^9/L, or <70 × 10^9/L if thrombocytopenia is considered by the investigator to be due to myeloma infiltration of bone marrow
- Aspartate aminotransferase [serum glutamic oxaloacetic transaminase] (AST [SGOT]) or alanine aminotransferase [serum glutamic-pyruvic transaminase] (ALT [SGPT]) >2× the upper limit of normal (ULN)
- Serum creatinine >2 mg/dL (>176.8 µmol/L); if the rise in creatinine is related to myeloma and there has been demonstrated a response to hydration, the subject may be enrolled.
- Myocardial infarction within 6 months prior to enrollment or New York Hospital Association Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or significant conduction system abnormalities in the opinion of the investigator. Prior to study entry, any abnormality on electrocardiogram at screening must be determined and documented by the investigator as not medically relevant.
- Any condition, including laboratory abnormalities, that in the opinion of the Investigator places the patient at unacceptable risk if he/she were to participate in the study. This includes but is not limited to serious medical conditions or psychiatric illness likely to interfere with participation in this clinical study.
- Prior malignancy except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, in situ breast cancer, in situ prostate cancer, or other cancer for which the patient has been disease-free for at least 3 years.
- Female who is pregnant or breastfeeding. Female participants of childbearing potential must have a negative pregnancy test with a sensitivity of at least 50 mIU/mL during Screening.
- Use of any investigational drugs within 30 days before randomization.
Trial locations and contacts
235 sites in 2 countries.
235 sites in 2 countries
United States234 sites
Texas Cancer Center
Abilene, Texas, 79606-5208
Stratton VA Medical Center IRB
Albany, New York, 12208
Christus St. Francis Cabrini Cancer Center
Alexandria, Louisiana, 71301
McFarland Clinic, P.C.
Ames, Iowa, 50010
Pacific Cancer Medical Centre
Anaheim, California, 92801
Annapolis Oncology Center
Annapolis, Maryland, 21401
Texas Oncology, P.A.
Arlington, Texas, 76014
Cancer Care & Hematology Specialists of Chicagoland
Arlington Heights, Illinois, 60005
Cancer Care of WNC
Asheville, North Carolina, 28801
Medical Oncology Associates of Augusta
Augusta, Georgia, 30901
Southwest Regional Cancer Center
Austin, Texas, 78705
Texas Oncology, PA
Austin, Texas, 78731
Greater Baltimore Medical Center
Baltimore, Maryland, 21204
St. Agnes Health Care
Baltimore, Maryland, 21229
Auerbach Hematology Oncology Associates
Baltimore, Maryland, 21237
Maryland Hematology Oncology Association
Baltimore, Maryland, 21237
Hematology-Oncology Clinic
Baton Rouge, Louisiana, 70809
Texas Oncology, PA
Beaumont, Texas, 77702
Texas Oncology, P.A.
Bedford, Texas, 76022
Center for Cancer and Blood Disorders
Bethesda, Maryland, 20817
Onc-Hem of Lehigh Valley, PC
Bethlehem, Pennsylvania, 18015
Tower Cancer Research Foundation
Beverly Hills, California, 90211-1850
Birmingham Hematology Oncology Assciates, LLC
Birmingham, Alabama, 35205
St. Alexius Clinical Research Services
Bismarck, North Dakota, 58501
The Center for Hematology-Oncology
Boca Raton, Florida, 33486
St. Lukes Mountain States Tumor Institute
Boise, Idaho, 83712
Boston Medical Center
Boston, Massachusetts, 02118
Pasco Hernando Oncology
Brooksville, Florida, 34613
Buffalo Institute for Medical Research, Inc.
Buffalo, New York, 14215
Erie County Medical Center
Buffalo, New York, 14215
Alamance Regional Medical Center
Burlington, North Carolina, 27215
The University of Vermont
Burlington, Vermont, 05401
Gabrail Cancer Center
Canton, Ohio, 44718
Desert Oasis Cancer Center
Casa Grande, Arizona, 85222
MUSC Hollings Cancer Center
Charleston, South Carolina, 29425
Chattanooga Oncology Hematology Associates
Chattanooga, Tennessee, 37404
Cancer Specialists of Tidewater
Chesapeake, Virginia, 23320
St. Louis Cancer Center
Chesterfield, Missouri, 63017
Hematology Oncology Associates of Illinois
Chicago, Illinois, 60611
John H. Stroger, Jr. Hospital of Cook County
Chicago, Illinois, 60612
University of Chicago
Chicago, Illinois, 60637
Hematology Oncology Associates of Illinois
Chicago, Illinois, 60657
Oncology Hematology Care, Inc.
Cincinnati, Ohio, 45215
Oncology Partners Network
Cincinnati, Ohio, 45247
University Hospitals of Cleveland
Cleveland, Ohio, 44106
Oncology-Hematology Associates, P.A.
Clinton, Maryland, 20735
The Family Cancer Center, PLLC
Collierville, Tennessee, 38017
Maryland Oncology Hematology, PA
Columbia, Maryland, 21044
Hematology Oncology Consultants Inc.
Columbus, Ohio, 43235
The Cancer Center of Cookeville Regional Medical Center
Cookeville, Tennessee, 38501
Northwest Oncology & Hematology Associates
Coral Springs, Florida, 33065
Compassionate Cancer Care Medical Group
Corona, California, 92882
Coastal Bend Cancer Center
Corpus Christi, Texas, 73112
South Texas Institute of Cancer and Blood Disorders
Corpus Christi, Texas, 78405
Heartland Hematology-Oncology Associates, Inc.
Council Bluffs, Iowa, 51503
Texas Oncology
Dallas, Texas, 75230-2510
Dallas Oncology Consultants
Dallas, Texas, 75237
Texas Oncology, PA / Methodist Charlton Cancer Center
Dallas, Texas, 75237
Texas Oncology PA
Dallas, Texas, 75246
Commonwealth Cancer Center
Danville, Kentucky, 40422
Dayton Clinical Oncology Program
Dayton, Ohio, 45429
Texas Cancer Center
Denton, Texas, 76210
Rocky Mountain Cancer Center
Denver, Colorado, 80218
Henry Ford Health System
Detroit, Michigan, 48202
St. Luke's Hospital
Duluth, Minnesota, 55805
Hematology & Oncology Associates of NEPA
Dunmore, Pennsylvania, 18512
Veterans Affairs New Jersey Healthcare System
East Orange, New Jersey, 07018
Puget Sound Cancer Center - Edmonds
Edmonds, Washington, 98026
El Paso Cancer Treatment Center
El Paso, Texas, 79902
Elmhurst Memorial Hospital
Elmhurst, Illinois, 60126
Drs. Forte, Schleider, Attas and Condemi, PA
Englewood, New Jersey, 07631
Willamette Valley Cancer Center
Eugene, Oregon, 97401
Deaconess Clinic Incorporated
Evansville, Indiana, 47713
Providence Everett Medical Center
Everett, Washington, 98201
Fairfax/Northern Virginia Hematology/Oncology
Fairfax, Virginia, 22031
Blood and Cancer Clinic
Fayetteville, North Carolina, 28304
Florida Cancer Specialists
Fort Myers, Florida, 33901
Texas Cancer Center
Fort Worth, Texas, 76104
Compassionate Cancer Care Medical Group, Inc.
Fountain Valley, California, 92708
Robert A. Moss, MD, FACP, Inc.
Fountain Valley, California, 92708
Cancer Care Associates
Fresno, California, 93720
Texas Oncology, PA
Garland, Texas, 75042
Gaston Hematology & Oncology
Gastonia, North Carolina, 28054
The Jones Clinic
Germantown, Tennessee, 38138
Glendale Memorial Hospital & Health Center
Glendale, California, 91204
Goshen Medical Associates
Goshen, New York, 10924
Cancer & Hematology Centers of Western Michigan
Grand Rapids, Michigan, 49546
Lee C. Drinkard, MD
Grapevine, Texas, 76051
Great Falls Clinic, LLP
Great Falls, Montana, 59405
California Cancer Care
Greenbrae, California, 94904
Cancer Center of the Carolinas
Greenville, South Carolina, 29605
Oncology Hematology Associates of North Illinois Ltd.
Gurnee, Illinois, 60031-3399
Kentucky Cancer Clinic
Hazard, Kentucky, 41701
Las Vegas Cancer Center
Henderson, Nevada, 89052
Carolina Oncology Specialist, PA
Hickory, North Carolina, 28603
Emerywood Hematology/Oncology
High Point, North Carolina, 27262
Beaver Medical Group
Highland, California, 92346
Horizon Institute for Clinical Research
Hollywood, Florida, 33021
Heritage Physician Group Oncology
Hot Springs, Arkansas, 71913
Houston Cancer Institute
Houston, Texas, 77055
Medicus Alliance Clinical Research Organization, LLC
Houston, Texas, 77090
Huntington Medical Group
Huntington Station, New York, 11746
Snake River Oncology of Eastern Idaho, PLLC.
Idaho Falls, Idaho, 83404
Central Indiana Cancer Centers
Indianapolis, Indiana, 46227
Investigative Clinical Research of Indiana, LLC
Indianapolis, Indiana, 46254
Baptist Cancer Institute
Jacksonville, Florida, 32207
University of Florida- Jacksonville
Jacksonville, Florida, 32209
Capital Region Medical Center/Cancer Center
Jefferson City, Missouri, 65109
Midwest Center for Hematology / Oncology
Joliet, Illinois, 60432
Joliet Oncology-Hematology Associates, Ltd.
Joliet, Illinois, 60435
Kalamazoo Hematology and Oncology
Kalamazoo, Michigan, 49048
Heartland Hematology-Oncology Associates, Inc.
Kansas City, Missouri, 64118
Kansas City Veterans Administration Medical Center
Kansas City, Missouri, 64128
Dayton Oncology & Hematology
Kettering, Ohio, 45409
Medical Oncology Associates
Kingston, Pennsylvania, 18704
East Tennessee Oncology/Hematology
Knoxville, Tennessee, 37920
University of Tennesee Medical Center
Knoxville, Tennessee, 37920
Gundersen Clinic, Ltd.
La Crosse, Wisconsin, 54601
Clarian Arnett Cancer Center
Lafayette, Indiana, 47904
Edward A. Wagner, MD
Laguna Beach, California, 92882
Cancer Care of North Florida
Lake City, Florida, 32024
North Shore-Long Island Jewish Health System
Lake Success, New York, 11042
Lakeland Regional Cancer Center
Lakeland, Florida, 33805
Hematology Oncology Associates of Ohio & Michigan, PC
Lambertville, Michigan, 48144
Regional Hematology Oncology Associates
Langhorne, Pennsylvania, 19047
Breslin Cancer Center / Great Lakes Cancer Institute
Lansing, Michigan, 48910
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, 89169
Cancer & Blood Disease Center
Lecanto, Florida, 34461
Lake Vista Cancer Center
Lewisville, Texas, 75067
Hematology Oncology Services of Arkansas
Little Rock, Arkansas, 72205
St. Barnabas Medical Center
Livingston, New Jersey, 07039
Longview Cancer Center
Longview, Texas, 75601
Lynchburg Hematology Oncology Clinic, Inc.
Lynchburg, Virginia, 24501
Central Georgia Cancer Care
Macon, Georgia, 31201
Northwest Georgia Oncology Centers, P.C.
Marietta, Georgia, 30060
Texas Cancer Center of Mesquite
Mesquite, Texas, 75150
Texas Oncology, P.A.
Midland, Texas, 79701
Metro MN CCOP
Minneapolis, Minnesota, 55416
Clinical Trials and Research Associates, Inc.
Montebello, California, 90640
Low Country Hematology & Oncology
Mt. Pleasant, South Carolina, 29464
Medical Consultants, PC
Muncie, Indiana, 47303
Hematology Oncology Consultants, Inc.
Naperville, Illinois, 60540
Sarah Cannon Research Institute
Nashville, Tennessee, 37203
Cancer Care Center
New Albany, Indiana, 47150
Arena Oncology Associates
New Hyde Park, New York, 11042
Pasco Hernando Oncology
New Port Richey, Florida, 34652
Florida Cancer Institute
New Port Richey, Florida, 34655
Memorial Sloan Kettering Cancer Center
New York, New York, 10021
New York Presbyterian Hospital-Cornell Campus
New York, New York, 10021
Christiana Care Health Services
Newark, Delaware, 19718
Newark Beth Israel Hospital
Newark, New Jersey, 07112
Peninsula Cancer Institute Riverside Cancer Center
Newport News, Virginia, 23601
Cancer Care and Hematology Specialists of Chicagoland
Niles, Illinois, 60714
Virginia Oncology Associates
Norfolk, Virginia, 23502
Mid-Illinois Hem & Onc
Normal, Illinois, 61761
Innovative Medical Research of South Florida Inc.
North Miami Beach, Florida, 33179
Great Plains Regional Medical Center
North Platte, Nebraska, 69101
Ocala Oncology Center
Ocala, Florida, 34474
Cancer Centers of Florida, P.A.
Ocoee, Florida, 34761
Texas Oncology - Odessa
Odessa, Texas, 79761
Northern Utah Associates
Ogden, Utah, 84403
Cancer Care Associates
Oklahoma City, Oklahoma, 73112
Creighton Cancer Center
Omaha, Nebraska, 68131-2137
Medical Oncology Care Associates
Orange, California, 92868
MD Anderson Cancer Center Orlando
Orlando, Florida, 32806
Kansas City Cancer Centers - Southwest
Overland Park, Kansas, 66210
Ventura County Hematology Oncology Specialists
Oxnard, California, 93030
Western Kentucky Hematology and Oncology Group
Paducah, Kentucky, 42003
Paris Regional Cancer Center
Paris, Texas, 75460
Greater Philadelphia Cancer and Hematology Specialists, PC
Philadelphia, Pennsylvania, 19114
UPMC Cancer Pavillioin
Pittsburgh, Pennsylvania, 15232
Hematology Oncology Associates of the Treasure Coast, PA
Port Saint Lucie, Florida, 34952
Southwest Cancer Care
Poway, California, 92064
Roger Williams Medical Center
Providence, Rhode Island, 02908
Quincy Medical Group
Quincy, Illinois, 62301
Raleigh Hematology Oncology / Associates, P.C.
Raleigh, North Carolina, 27607
Desert Cancer Care, Incorporated
Rancho Mirage, California, 92270
Virginia Cancer Institute
Richmond, Virginia, 23230
Compassionate Cancer Care Medical Group, Inc.
Riverside, California, 92501
Hubert H. Humphrey Cancer Center
Robbinsdale, Minnesota, 55422
Interlakes Foundation, Inc.
Rochester, New York, 14623
Sutter Cancer Center
Sacramento, California, 95816
Oncology Care Associates, P.L.L.C.
Saint Joseph, Michigan, 49085
St. Joseph Oncology
Saint Joseph, Missouri, 64507
Oncology and Hematology Associates of Southwest Virginia, Inc.
Salem, Virginia, 24153
Utah Cancer Specialists
Salt Lake City, Utah, 84106
Cancer Care Network of South Texas
San Antonio, Texas, 78217
Cancer Care Center of South Texas
San Antonio, Texas, 78229
CTRC Institute for Drug Development
San Antonio, Texas, 78245
New Mexico Cancer Care Associates
Santa Fe, New Mexico, 87505
Summit Cancer Care
Savannah, Georgia, 31405
Guthrie Research Institute
Sayre, Pennsylvania, 18840
Scranton Hematology Oncology
Scranton, Pennsylvania, 18510
Puget Sound Cancer Center, Inc
Seattle, Washington, 98133
Northern Arizona Hematology & Oncology Associates - AOA
Sedona, Arizona, 86336
Texas Cancer Center - Sherman
Sherman, Texas, 75090
Siouxland Hematology/Oncology Assoc., LLP
Sioux City, Iowa, 51101
Avera Research Institute
Sioux Falls, South Dakota, 57105
Somerset Hematology Oncology Associates
Somerville, New Jersey, 08876
Cancer Research & Prevention Center
Soquel, California, 95073
Memorial Hospital of South Bend
South Bend, Indiana, 46601
Providence Cancer Center
Southfield, Michigan, 48075
Cancer Center of Central Connecticut
Southington, Connecticut, 06489
Sparta Cancer Center
Sparta, New Jersey, 07871
Cancer Care Northwest, US Oncology
Spokane, Washington, 99202
Gulfcoast Oncology Associates
St. Petersburg, Florida, 33705
Richmond University Medical Center
Staten Island, New York, 10301
Stockton Hematology/Oncology
Stockton, California, 95204
Santee Hematology/Oncology
Sumter, South Carolina, 29150
SUNY Upstate Medical University
Syracuse, New York, 13210
Northwest Medical Specialties, PLLC
Tacoma, Washington, 98405
Hope Center
Terre Haute, Indiana, 47802
Eastchester Center for Cancer Care
The Bronx, New York, 10469
Toledo Community Hospital Oncology Program
Toledo, Ohio, 43617
Arizona Oncology Associates
Tucson, Arizona, 85704
Oklahoma Oncology and Hematology
Tulsa, Oklahoma, 74136
Blood and Cancer Center of East Texas
Tyler, Texas, 75701
Tyler Hematology/Oncology, PA
Tyler, Texas, 75701
Texas Oncology, PA
Tyler, Texas, 75702
New York Medical College
Valhalla, New York, 10595
Texas Oncology
Waco, Texas, 76712
Wenatchee Valley Medical Center
Wenatchee, Washington, 98801
Alyce & Elmore Kraemer Cancer Center
West Bend, Wisconsin, 53095
S. Florida Oncology/ Hematology
West Palm Beach, Florida, 33458
Trivalley Oncology Hematology
Westlake Village, California, 91361
Carroll County Cancer Center
Westminster, Maryland, 21157
White River Junction VAMC
White River Junction, Vermont, 05009-001
Cancer Center of Kansas
Wichita, Kansas, 67214
Hanover Medical Specialists, P.A.
Wilmington, North Carolina, 28401
Masoom Kandahari, MD, PC
Woodbridge, Virginia, 22191
Osteopathic Medical Hematology & Oncology
Woodhaven, Michigan, 48183
Trilogy Cancer Center
Wooster, Ohio, 44691
Fallon Clinic at Worcester Medical Center
Worcester, Massachusetts, 01608-1320
Yakima Valley Memorial Hospital / North Star Lodge
Yakima, Washington, 98902
Puerto Rico1 site
Hospital Auxillo Mutuo, Auxilio Mutuo Cancer Center
San Juan, 00919-1227
About this study
Official title: Randomized Phase 3b Study of Three Treatment Regimens in Subjects With Previously Untreated Multiple Myeloma Who Are Not Considered Candidates for High-Dose Chemotherapy and Autologous Stem Cell Transplantation: VELCADE, Thalidomide, and Dexamethasone Versus VELCADE and Dexamethasone Versus VELCADE, Melphalan, and Prednisone
This is a randomized, open label, multicenter clinical trial to compare the efficacy and safety of Velcade (bortezomib) and dexamethasone versus Velcade, thalidomide, and dexamethasone versus Velcade, melphalan, and prednisone in patients with previously untreated multiple myeloma not considered candidates for high-dose chemotherapy and autologous stem cell transplantation.
- Conditions
- Multiple Myeloma
- Being tested
- Bortezomib, Dexamethasone, Melphalan, Prednisone, Thalidomide
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BortezomibDrug
Also called Velcade
Bortezomib bolus intravenous (IV) injection
DexamethasoneDrug
Dexamethasone for oral administration
MelphalanDrug
Melphalan for oral administration
PrednisoneDrug
Prednisone for oral administration
ThalidomideDrug
Thalidomide for oral administration
| Study group | Role | What they receive |
|---|---|---|
| Bortezomib and Dexamethasone (VD) | Experimental | Participants received bortezomib (Velcade) 1.3 mg/m^2 administered as a bolus intravenous (IV) injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance). Receives: Drug: Bortezomib; Drug: Dexamethasone |
| Bortezomib, Thalidomide, and Dexamethasone (VTD) | Experimental | Participants received bortezomib (Velcade) 1.3 mg/m^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12, and thalidomide 100 mg orally on Days 1-21 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance) . Receives: Drug: Bortezomib; Drug: Dexamethasone; Drug: Thalidomide |
| Bortezomib, Melphalan and Prednisone (VMP) | Experimental | Participants received bortezomib (Velcade) 1.3 mg/m^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and melphalan 9 mg/m^2 orally on Days 1-4 every other cycle and prednisone 60 mg/m^2 orally on Days 1-4 every other cycle for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance). Receives: Drug: Bortezomib; Drug: Melphalan; Drug: Prednisone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival (PFS)
PFS is defined as the time from randomization to disease progression or death, whichever occurs first. Participants who did not progress and were still alive at the cut-off date were censored at the date of last contact. Response was assessed by the Investigator using the International Myeloma Working Group (IMWG) uniform response criteria.
Progressive disease requires 1 of the following:
- Increase of ≥ 25% from nadir in:
- Serum M-component (absolute increase ≥ 0.5 g/dl)
- Urine M-component (absolute increase ≥ 200 mg/24 hours)
- In patients without measurable serum and urine M-protein levels the difference between involved and uninvolved free light chain (FLC) levels (absolute increase > 100 mg/dl)
- Bone marrow plasma cell percentage (absolute % ≥ 10%)
- Development of new or increase in the size of existing bone lesions or soft tissue plasmacytomas.
- Development of hypercalcemia (corrected serum calcium > 11.5 mg/dl) attributed solely to plasma cell proliferative disease
Measured: From randomization until disease progression. Median follow-up time was 43 months.
Secondary outcomes (7)
Percentage of Participants With an Overall Response
Overall response defined as a best overall response of complete response (CR), very good partial response (VGPR) or partial response (PR), assessed by the Investigator using the IMWG uniform response criteria.
CR: Negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas, and <5% plasma cells in bone marrow.
VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein plus urine M-protein level <100 mg per 24 hours (h).
PR requires 1 of the following:
- ≥50% reduction of serum M-protein and 24-h urinary M-protein by ≥ 90% or to <200 mg/24 h, or
- If M-protein not measurable, a ≥50% decrease in the difference between involved and uninvolved FLC levels, or
- If FLC not measurable, a ≥ 50% reduction in plasma cells, provided baseline bone marrow plasma cell percentage was ≥30%.
If present at baseline, a ≥50% reduction in the size of soft tissue plasmacytomas is also required.
Measured: Response assessed every other cycle for up to 13 cycles (49 weeks).
Percentage of Participants With a Complete Response
Participants with a best overall response of complete response, defined as negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas, and <5% plasma cells in bone marrow. Response was assessed by the Investigator using the IMWG uniform response criteria.
Measured: Response assessed every other cycle, for up to 13 cycles (49 weeks).
Percentage of Participants With a Complete Response or a Very Good Partial Response
Complete response is defined by negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas, and <5% plasma cells in bone marrow.
Very good partial response is defined by serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level <100 mg per 24 hours.
Response was assessed by the Investigator using the IMWG uniform response criteria.
Measured: Response assessed every other cycle for up to 13 cycles (49 weeks).
Duration of Response
Duration of response is defined in participants with an overall response as the time between first documentation of response and disease progression. Responders without disease progression were censored at the last clinical assessment of response.
Measured: From first documented response until disease progression. Median follow-up time was 43 months.
Overall Survival
Overall survival is defined as the time between randomization and death. Participants still alive at the cutoff date or lost to follow-up were censored at the date of last contact.
Measured: From randomization until death. Median follow-up time was 43 months.
Time to Alternative Therapy
Time to alternative therapy is defined as the time between randomization and alternative therapy. Participants who did not receive alternative therapy were censored at the time of last contact.
Measured: From randomization until alternative therapy. Median follow-up time was 43 months.
Change From Baseline in EORTC QLQ-C30 - Global Health Status
The European Organisation for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact).
The EORTC QLQ-C30 Global Health Status/QOL Scale is scored between 0 and 100, where higher scores indicate better Global Health Status/QOL. Negative changes from baseline indicate deterioration in QOL or functioning and positive changes indicate improvement.
Measured: Baseline and Day 1 of Cycles 3, 5, 7, 9, 11 and 13
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jul 2007 (estimated)
- Study startJun 2007
- Primary completionMar 2013
- Study completionMar 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 502 participants (actual)
Sponsor and investigators
- Lead sponsor
- Millennium Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Monitor, Study director, Millennium Pharmaceuticals, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00507416
- Sponsor's protocol ID
- C05009
- Acronym
- UPFRONT
- Status last verified
- Mar 2014
- First submitted
- 25 Jul 2007
- Last updated
- 1 May 2014
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Niesvizky R, Flinn IW, Rifkin R, Gabrail N, Charu V, Clowney B, Essell J, Gaffar Y, Warr T, Neuwirth R, Zhu Y, Elliott J, Esseltine DL, Niculescu L, Reeves J. Community-Based Phase IIIB Trial of Three UPFRONT Bortezomib-Based Myeloma Regimens. J Clin Oncol. 2015 Nov 20;33(33):3921-9. doi: 10.1200/JCO.2014.58.7618. Epub 2015 Jun 8.
PubMed 26056177
Study at a glance
From the registry record, last updated by the sponsor on 1 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Phase 3b Study of Three Treatment Regimens in Subjects With Previously Untreated Multiple Myeloma Who Are Not Considered Candidates for High-Dose Chemotherapy and Autologous Stem Cell Transplantation: VELCADE, Thalidomide, and Dexamethasone Versus VELCADE and Dexamethasone Versus VELCADE, Melphalan, and Prednisone
- ClinicalTrials.gov ID
- NCT00507416
- Acronym / sponsor ID
- UPFRONT / C05009
- Conditions
- Multiple Myeloma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 502 participants (actual)
- Lead sponsor
- Millennium Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- Jun 2007
- Primary completion
- Mar 2013 (actual)
- Study completion
- Mar 2013 (actual)
- First posted
- 26 Jul 2007 (estimated)
- Results
- Posted 1 May 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a randomized, open label, multicenter clinical trial to compare the efficacy and safety of Velcade (bortezomib) and dexamethasone versus Velcade, thalidomide, and dexamethasone versus Velcade, melphalan, and prednisone in patients with previously untreated multiple myeloma not considered candidates for high-dose chemotherapy and autologous stem cell transplantation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Bortezomib and Dexamethasone (VD) | Experimental | Drug: Bortezomib, Drug: DexamethasoneParticipants received bortezomib (Velcade) 1.3 mg/m^2 administered as a bolus intravenous (IV) injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance). |
| Bortezomib, Thalidomide, and Dexamethasone (VTD) | Experimental | Drug: Bortezomib, Drug: Dexamethasone, Drug: ThalidomideParticipants received bortezomib (Velcade) 1.3 mg/m^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12, and thalidomide 100 mg orally on Days 1-21 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance) . |
| Bortezomib, Melphalan and Prednisone (VMP) | Experimental | Drug: Bortezomib, Drug: Melphalan, Drug: PrednisoneParticipants received bortezomib (Velcade) 1.3 mg/m^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and melphalan 9 mg/m^2 orally on Days 1-4 every other cycle and prednisone 60 mg/m^2 orally on Days 1-4 every other cycle for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Male or female 18 years of age or older
- Not a candidate for high-dose chemotherapy and stem cell transplantation (HDT/SCT) due to age, presence of important comorbid condition(s) likely to have a negative impact on tolerability of HDT-SCT, or subject preference.
- A Karnofsky Performance Status score of ≥50%
- Symptomatic multiple myeloma or asymptomatic multiple myeloma with related organ or tissue damage.
- Asymptomatic multiple myeloma-related organ or tissue damage can include presence of an asymptomatic lytic bone lesion or plasmacytoma, the presence of anemia (hemoglobin <10 g/dL), renal function impairment (serum creatinine > upper limit of normal [ULN]) or hypercalcemia (serum calcium >ULN).
Key exclusion criteria (17 listed)
- Diagnosis of smoldering multiple myeloma or monoclonal gammopathy of undetermined significance (MGUS). Smoldering multiple myeloma is defined as asymptomatic multiple myeloma with absence of lytic bone lesions. MGUS is defined by presence of serum monoclonal protein <3 g/dL; absence of lytic bone lesions, anemia, hypercalcemia, and renal insufficiency related to the monoclonal protein; and (if determined) proportion of plasma cells in the bone marrow of 10% or less.
- Diagnosis of Waldenström's disease or other conditions in which immunoglobulin M (IgM) M-protein is present in the absence of a clonal plasma cell infiltration or lytic bone lesions.
- Previously or currently treated with any systemic therapy for multiple myeloma. Prior treatment of hypercalcemia or spinal cord compression with corticosteroids or radiation therapy, respectively, does not disqualify the subject (the dose of corticosteroids should not exceed the equivalent of 160 mg of dexamethasone in 2-week period).
- Radiation therapy within 2 weeks before randomization. Enrollment of patients who require concurrent radiotherapy (which must be localized in its field size) should be deferred until the radiotherapy is completed and 2 weeks have elapsed since the last date of therapy.
- Major surgery within 30 days before randomization (Kyphoplasty is not considered major surgery)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BortezomibAlso: VelcadeBortezomib bolus intravenous (IV) injection | Drug | Bortezomib and Dexamethasone (VD), Bortezomib, Melphalan and Prednisone (VMP), Bortezomib, Thalidomide, and Dexamethasone (VTD) |
| DexamethasoneDexamethasone for oral administration | Drug | Bortezomib and Dexamethasone (VD), Bortezomib, Thalidomide, and Dexamethasone (VTD) |
| MelphalanMelphalan for oral administration | Drug | Bortezomib, Melphalan and Prednisone (VMP) |
| PrednisonePrednisone for oral administration | Drug | Bortezomib, Melphalan and Prednisone (VMP) |
| ThalidomideThalidomide for oral administration | Drug | Bortezomib, Thalidomide, and Dexamethasone (VTD) |
Primary outcome
Progression Free Survival (PFS)
Time frame: From randomization until disease progression. Median follow-up time was 43 months.
PFS is defined as the time from randomization to disease progression or death, whichever occurs first. Participants who did not progress and were still alive at the cut-off date were censored at the date of last contact. Response was assessed by the Investigator using the International Myeloma Working Group (IMWG) uniform response criteria. Progressive disease requires 1 of the following: * Increase of ≥ 25% from nadir in: * Serum M-component (absolute increase ≥ 0.5 g/dl) * Urine M-component (absolute increase ≥ 200 mg/24 hours) * In patients without measurable serum and urine M-protein levels the difference between involved and uninvolved free light chain (FLC) levels (absolute increase > 100 mg/dl) * Bone marrow plasma cell percentage (absolute % ≥ 10%) * Development of new or increase in the size of existing bone lesions or soft tissue plasmacytomas. * Development of hypercalcemia (corrected serum calcium > 11.5 mg/dl) attributed solely to plasma cell proliferative disease
7 secondary outcomes
Percentage of Participants With an Overall Response
Time frame: Response assessed every other cycle for up to 13 cycles (49 weeks).
Percentage of Participants With a Complete Response
Time frame: Response assessed every other cycle, for up to 13 cycles (49 weeks).
Percentage of Participants With a Complete Response or a Very Good Partial Response
Time frame: Response assessed every other cycle for up to 13 cycles (49 weeks).
Duration of Response
Time frame: From first documented response until disease progression. Median follow-up time was 43 months.
Overall Survival
Time frame: From randomization until death. Median follow-up time was 43 months.
Time to Alternative Therapy
Time frame: From randomization until alternative therapy. Median follow-up time was 43 months.
Change From Baseline in EORTC QLQ-C30 - Global Health Status
Time frame: Baseline and Day 1 of Cycles 3, 5, 7, 9, 11 and 13
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 May 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26056177Niesvizky R, Flinn IW, Rifkin R, Gabrail N, Charu V, Clowney B, Essell J, Gaffar Y, Warr T, Neuwirth R, Zhu Y, Elliott J, Esseltine DL, Niculescu L, Reeves J. Community-Based Phase IIIB Trial of Three UPFRONT Bortezomib-Based Myeloma Regimens. J Clin Oncol. 2015 Nov 20;33(33):3921-9. doi: 10.1200/JCO.2014.58.7618. Epub 2015 Jun 8.
Related trials for Multiple Myeloma
Not yet recruitingPhase 2
Study of YKST02 in Adults With Relapsed or Refractory Multiple Myeloma
Relapsed or Refractory Multiple Myeloma (RRMM)
RecruitingPhase 2
Engaging T-cells to Eliminate MRD in Newly Diagnosed Myeloma Optimizing Response With Talquetmab and Teclistamab (ROTATE)
Multiple Myeloma
Active, not recruitingPhase 3
A Phase III Study of Eque-cel in Subjects With Len-refractory RRMM (FUMANBA-03)
Multiple Myeloma
Active, not recruitingPhase 1/2
A Window of Opportunity Trial to Learn if Linvoseltamab is Safe and Well Tolerated, and How Well it Works in Adult Participants With Recently Diagnosed Multiple Myeloma Who Have Not Already Received Treatment
Multiple Myeloma
Active, not recruitingPhase 2
Testing AZD5363 as a Potential Targeted Treatment in Cancers With AKT Genetic Changes (MATCH-Subprotocol Y)
Advanced Lymphoma, Advanced Malignant Solid Neoplasm
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Monitor study director
Millennium Pharmaceuticals, Inc.
235 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Bortezomib, Dexamethasone and Melphalan in people with Multiple Myeloma, run by Millennium Pharmaceuticals, Inc. at 235 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 May 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 235 sites in United States, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 May 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression Free Survival (PFS) (time frame: From randomization until disease progression. Median follow-up time was 43 months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00507416, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 May 2014.