S1304, Carfilzomib and Dexamethasone for Treating Patients With Relapsed or Refractory Myeloma

Recurrent Plasma Cell Myeloma Clinical Trial

Official title:

A Phase II Randomized Study Comparing Two Doses of Carfilzomib (NSC-756640) With Dexamethasone for Multiple Myeloma Patients With Relapsed or Refractory Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01903811
• Other study ID #: S1304
• Secondary ID: NCI-2013-00796PS
• Status: Completed
• Phase: Phase 2
• Start date: October 2013
• Est. completion date: March 7, 2019

Study information

• Verified date: April 2020
• Source: Southwest Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This randomized phase II trial compares how well two different doses of carfilzomib work when given with dexamethasone in treating patients with multiple myeloma that has come back after a period of improvement or has not responded to treatment. Carfilzomib 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, by stopping them from dividing, or by stopping them from spreading. Giving carfilzomib together with dexamethasone may kill more cancer cells. It is not yet known whether a higher or lower dose of carfilzomib works better when given with dexamethasone.

Description:

PRIMARY OBJECTIVES:

I. To evaluate and compare progression free survival (PFS) of two different doses of carfilzomib with dexamethasone in multiple myeloma (MM) patients with relapsed and/or refractory disease.

SECONDARY OBJECTIVES:

I. To evaluate and compare response rates (RR) for each arm. II. To evaluate response rates (RR) for patients that relapse on low dose carfilzomib and subsequently cross-over to high dose carfilzomib.

III. To evaluate the safety of this combination for this patient population. IV. To evaluate overall survival (OS).

TERTIARY OBJECTIVES:

I. To explore the molecular variability in MM cells obtained from extramedullary bone marrow relapse sites.

II. To explore the role of positron emission tomography (PET) scanning in assessing disease burden and as a tool to assess treatment response.

III. To explore changes in left ventricular ejection fraction (LVEF) in patients with relapsed or refractory multiple myeloma treated with low dose carfilzomib or high dose carfilzomib plus dexamethasone.

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

ARM I: Patients receive dexamethasone intravenously (IV) and low-dose carfilzomib IV over 2-10 minutes on days 1, 2, 8, 9, 15, and 16. Patients with progression cross-over to Arm II.

ARM II: Patients receive dexamethasone IV and high-dose carfilzomib IV over 30 minutes on days 1, 2, 8, 9, 15, and 16.

Note that for the first course of treatment on both arms carfilzomib is given at a reduced rate to assess toxicity.

In both arms, treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 3 years from initial registration.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 143
• Est. completion date: March 7, 2019
• Est. primary completion date: November 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• REGISTRATION STEP 1: INITIAL RANDOMIZATION

• Patients must have a confirmed diagnosis of symptomatic multiple myeloma and must be currently relapsed or refractory; all tests for establishing disease status must be completed within 28 days prior to registration and documented on the Baseline Tumor Assessment Form for Multiple Myeloma

• Patients must have measurable disease within 28 days prior to registration

• Patients must have received at least one prior regimen of chemotherapy for symptomatic multiple myeloma; patients may not have more than six (6) previous regimens of therapy for the disease; prior chemotherapy must have been completed at least 21 days prior to registration; for study purposes, a regimen is defined as follows:

• An anti-myeloma therapy used at the time of initial diagnosis or documented disease progression which is given with the intent to decrease disease burden

• Any maintenance therapy used after an Induction should be considered part of that Induction regimen

• Use of any agent or combination of agents more than once during the patient's disease history for separate documented disease progressions will be counted as separate regimens (e.g., if a patient receives lenalidomide/bortezomib at initial diagnosis and achieves response, but then progresses and receives lenalidomide/bortezomib after progression, these count as 2 separate regimens)

• In cases of allogeneic or autologous stem cell transplant, the entire induction + stem cell mobilization + conditioning + planned maintenance should be considered one regimen

• Patients may not have received any prior carfilzomib treatment

• Patients must not be receiving any other concurrent therapy considered to be investigational; patients must not be planning to receive any radiotherapy (except localized radiation for palliative care); patients must not be planning to receive any concurrent chemotherapy, immunotherapy, radiotherapy or other treatment with curative intent

• Patients must have complete history and physical examination within 28 days prior to registration

• Patients must have baseline PET scan within 28 days prior to registration; note that images are submitted centrally for review

• Patients with non-secretory MM or known primary amyloidosis are not eligible

• Patients must have Zubrod performance status 0-2

• Patients must not have clinically significant illness including uncontrolled, active infection requiring intravenous antibiotics, New York Heart Association (NYHA) class III or class IV heart failure, unstable angina pectoris, myocardial infarction within the past 6 months, or >= grade 3 cardiac arrhythmias

• Patients must have undergone an electrocardiogram (EKG) within 28 days prior to registration

• Patients must have either echocardiogram (ECHO) with ejection fraction >= 45% within 28 days prior to registration

• Patients must not have > grade 2 neuropathy and/or POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)

• Total bilirubin =< 1.5 x upper limit of normal (ULN)

• Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) =< 3 x ULN

• Absolute neutrophil count (ANC) >= 1,000 cell/mm^3 without growth factor support within 14 days prior to registration

• Platelets >= 50,000 cells/mm^3 for patients who have bone marrow plasmacytosis < 50% or >= 30,000 cells/mm^3 for patients who have bone marrow plasmacytosis of >= 50% within 14 days prior to registration

• Calculated or measured creatinine clearance >= 30 ml/min within 14 days prior to registration

• Patients who are known to be human immunodeficiency virus positive (HIV+) are eligible providing they meet all of the following additional criteria within 28 days prior to registration:

• Cluster of differentiation (CD)4 cells >= 500/mm^3

• Viral load of < 50 copies HIV messenger ribonucleic acid (mRNA)/mm^3 if on combination antiretroviral therapy (cART) or < 25,000 copies HIV mRNA if not on cART

• No zidovudine or stavudine as part of cART

• Patients who are HIV+ and do not meet all of these criteria are not eligible for this study

• Patients with known hepatitis B or hepatitis C infection must have viral load < 800,000 IU/L within 28 days prior to registration

• Patients must have baseline skeletal survey to document lytic lesions, osteopenia or compression fracture within 28 days prior to registration

• Patients may have received palliative external beam radiation therapy (XRT) for local disease control with no curative intent. XRT must be completed at least 7 days prior to registration

• Patients must be offered participation in specimen submission for translational medicine studies and banking; with patient consent, specimens must be submitted

• Patients must not be pregnant or nursing; women/men of reproductive potential must have agreed to use an effective contraceptive method; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures

• No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for three years

• Patients or their legally authorized representative must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines

• As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system

• REGISTRATION STEP 2: CROSSOVER

• Patient must have been eligible for and initially randomized to Arm 1 (low dose carfilzomib), begun cycle 2 of treatment, and progressed prior to completing 12 cycles of protocol therapy

• At least 14 days and no more than 28 days must have elapsed between the last day of treatment on Arm 1 and registration to Arm 3

• Patients must have recovered from all non-hematologic toxicities to =< grade 2 and from all hematologic toxicities to =< grade 3 prior to registration

• Patients must have begun cycle 2 (carfilzomib - 27 mg/m^2) and must not have received any dose reduction for toxicity in the last cycle of treatment, immediately preceding progression

• Patients must have serum protein electrophoresis (SPEP) and kappa and lambda light chain testing performed within 14 days prior to registration in order to establish baseline measurements

• Patients must not have ejection fraction decrease > 10% from baseline (as determined by ECHO) or other ejection fraction decrease accompanied by other clinical signs/symptoms of New York Heart Association (NYHA) class III or IV heart failure, measured within 28 days prior to registration; if any question exists regarding individual patient eligibility in this situation, contact the study chair for determination

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Recurrent Plasma Cell Myeloma
• Refractory Plasma Cell Myeloma

Intervention

Drug:
• Carfilzomib
Given IV
• Dexamethasone
Given IV

Other:
• Laboratory Biomarker Analysis
Correlative studies

Locations

Country	Name	City	State
United States	Hawaii Oncology Inc-Pali Momi	'Aiea	Hawaii
United States	Pali Momi Medical Center	'Aiea	Hawaii
United States	Bixby Medical Center	Adrian	Michigan
United States	Hickman Cancer Center	Adrian	Michigan
United States	Mary Greeley Medical Center	Ames	Iowa
United States	McFarland Clinic PC-William R Bliss Cancer Center	Ames	Iowa
United States	Kaiser Permanente-Anaheim	Anaheim	California
United States	AnMed Health Cancer Center	Anderson	South Carolina
United States	Michigan Cancer Research Consortium NCORP	Ann Arbor	Michigan
United States	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	Kaiser Permanente-Deer Valley Medical Center	Antioch	California
United States	Randolph Hospital	Asheboro	North Carolina
United States	Sutter Auburn Faith Hospital	Auburn	California
United States	Sutter Cancer Centers Radiation Oncology Services-Auburn	Auburn	California
United States	Harold Alfond Center for Cancer Care	Augusta	Maine
United States	Rush - Copley Medical Center	Aurora	Illinois
United States	Kaiser Permanente-Baldwin Park	Baldwin Park	California
United States	Eastern Maine Medical Center	Bangor	Maine
United States	Hematology/Oncology Clinic LLP	Baton Rouge	Louisiana
United States	Louisiana Hematology Oncology Associates LLC	Baton Rouge	Louisiana
United States	LSU Health Baton Rouge-North Clinic	Baton Rouge	Louisiana
United States	Mary Bird Perkins Cancer Center	Baton Rouge	Louisiana
United States	Medical Oncology LLC	Baton Rouge	Louisiana
United States	Kaiser Permanente-Bellflower	Bellflower	California
United States	Strecker Cancer Center-Belpre	Belpre	Ohio
United States	Sanford Clinic North-Bemidgi	Bemidji	Minnesota
United States	Alta Bates Summit Medical Center-Herrick Campus	Berkeley	California
United States	Constantinou, Costas L MD (UIA Investigator)	Bettendorf	Iowa
United States	Hematology Oncology Associates-Quad Cities	Bettendorf	Iowa
United States	Beverly Hospital	Beverly	Massachusetts
United States	Billings Clinic Cancer Center	Billings	Montana
United States	Montana Cancer Consortium NCORP	Billings	Montana
United States	Saint Vincent Healthcare	Billings	Montana
United States	Sanford Bismarck Medical Center	Bismarck	North Dakota
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	Saint Joseph Medical Center	Bloomington	Illinois
United States	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho
United States	Central Care Cancer Center-Carrie J Babb Cancer Center	Bolivar	Missouri
United States	Parkland Health Center-Bonne Terre	Bonne Terre	Missouri
United States	McFarland Clinic PC-Boone	Boone	Iowa
United States	Boston Medical Center	Boston	Massachusetts
United States	Toledo Clinic Cancer Centers-Bowling Green	Bowling Green	Ohio
United States	Bozeman Deaconess Hospital	Bozeman	Montana
United States	CoxHealth Cancer Center	Branson	Missouri
United States	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania
United States	Mills - Peninsula Hospitals	Burlingame	California
United States	Aurora Cancer Care-Southern Lakes VLCC	Burlington	Wisconsin
United States	Cone Health Cancer Center at Alamance Regional	Burlington	North Carolina
United States	Lahey Hospital and Medical Center	Burlington	Massachusetts
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana
United States	Sutter Cancer Centers Radiation Oncology Services-Cameron Park	Cameron Park	California
United States	Aultman Health Foundation	Canton	Ohio
United States	Illinois CancerCare-Canton	Canton	Illinois
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Southeast Cancer Center	Cape Girardeau	Missouri
United States	Memorial Hospital of Carbondale	Carbondale	Illinois
United States	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Rocky Mountain Oncology	Casper	Wyoming
United States	Eden Hospital Medical Center	Castro Valley	California
United States	Miami Valley Hospital South	Centerville	Ohio
United States	Centralia Oncology Clinic	Centralia	Illinois
United States	Cancer Center of Kansas - Chanute	Chanute	Kansas
United States	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	Saint Luke's Hospital	Chesterfield	Missouri
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	Marshfield Clinic-Chippewa Center	Chippewa Falls	Wisconsin
United States	Oncology Hematology Care Inc - Anderson	Cincinnati	Ohio
United States	Oncology Hematology Care Inc-Blue Ash	Cincinnati	Ohio
United States	Oncology Hematology Care Inc-Eden Park	Cincinnati	Ohio
United States	Oncology Hematology Care Inc-Kenwood	Cincinnati	Ohio
United States	Oncology Hematology Care Inc-Mercy West	Cincinnati	Ohio
United States	Southeastern Medical Oncology Center-Clinton	Clinton	North Carolina
United States	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa
United States	Mercy Cancer Center-West Lakes	Clive	Iowa
United States	Big Horn Basin Cancer Center	Cody	Wyoming
United States	Billings Clinic-Cody	Cody	Wyoming
United States	Kootenai Medical Center	Coeur d'Alene	Idaho
United States	Columbus NCI Community Oncology Research Program	Columbus	Ohio
United States	Columbus Oncology and Hematology Associates Inc	Columbus	Ohio
United States	Doctors Hospital	Columbus	Ohio
United States	Grant Medical Center	Columbus	Ohio
United States	Mount Carmel East Hospital	Columbus	Ohio
United States	Mount Carmel Health Center West	Columbus	Ohio
United States	Riverside Methodist Hospital	Columbus	Ohio
United States	The Mark H Zangmeister Center	Columbus	Ohio
United States	John Muir Medical Center-Concord Campus	Concord	California
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	Mary Bird Cancer Center/Saint Tammany Parish	Covington	Louisiana
United States	Oncology Hematology Care Inc-Crestview	Crestview Hills	Kentucky
United States	Carle on Vermilion	Danville	Illinois
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Genesis Medical Center - East Campus	Davenport	Iowa
United States	Sutter Davis Hospital	Davis	California
United States	Dayton NCI Community Oncology Research Program	Dayton	Ohio
United States	Good Samaritan Hospital - Dayton	Dayton	Ohio
United States	Miami Valley Hospital	Dayton	Ohio
United States	Samaritan North Health Center	Dayton	Ohio
United States	Beaumont Hospital-Dearborn	Dearborn	Michigan
United States	Cancer Care Center of Decatur	Decatur	Illinois
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Delaware Health Center-Grady Cancer Center	Delaware	Ohio
United States	Delaware Radiation Oncology	Delaware	Ohio
United States	Grady Memorial Hospital	Delaware	Ohio
United States	Smilow Cancer Hospital-Derby Care Center	Derby	Connecticut
United States	Iowa Lutheran Hospital	Des Moines	Iowa
United States	Iowa Methodist Medical Center	Des Moines	Iowa
United States	Iowa-Wide Oncology Research Coalition NCORP	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates-Laurel	Des Moines	Iowa
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Henry Ford Hospital	Detroit	Michigan
United States	Saint John Hospital and Medical Center	Detroit	Michigan
United States	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan
United States	Cancer Center of Kansas - Dodge City	Dodge City	Kansas
United States	Marshfield Clinic Cancer Center at Sacred Heart	Eau Claire	Wisconsin
United States	Sacred Heart Hospital	Eau Claire	Wisconsin
United States	Fairview-Southdale Hospital	Edina	Minnesota
United States	Carle Physician Group-Effingham	Effingham	Illinois
United States	Crossroads Cancer Center	Effingham	Illinois
United States	Cancer Center of Kansas - El Dorado	El Dorado	Kansas
United States	Green Bay Oncology - Escanaba	Escanaba	Michigan
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	Fairbanks Memorial Hospital	Fairbanks	Alaska
United States	Oncology Hematology Care Inc-Healthplex	Fairfield	Ohio
United States	Smilow Cancer Hospital Care Center-Fairfield	Fairfield	Connecticut
United States	Roger Maris Cancer Center	Fargo	North Dakota
United States	Sanford Clinic North-Fargo	Fargo	North Dakota
United States	Sanford Medical Center-Fargo	Fargo	North Dakota
United States	Weisberg Cancer Treatment Center	Farmington Hills	Michigan
United States	Blanchard Valley Hospital	Findlay	Ohio
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	McLeod Regional Medical Center	Florence	South Carolina
United States	Aurora Health Center-Fond du Lac	Fond Du Lac	Wisconsin
United States	Kaiser Permanente Hospital	Fontana	California
United States	McFarland Clinic PC-Trinity Cancer Center	Fort Dodge	Iowa
United States	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas
United States	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio
United States	Fredericksburg Oncology Inc	Fredericksburg	Virginia
United States	Kaiser Permanente-Fremont	Fremont	California
United States	Kaiser Permanente	Fresno	California
United States	Unity Hospital	Fridley	Minnesota
United States	University of Florida	Gainesville	Florida
United States	Illinois CancerCare-Galesburg	Galesburg	Illinois
United States	Western Illinois Cancer Treatment Center	Galesburg	Illinois
United States	Aurora Health Care Germantown Health Center	Germantown	Wisconsin
United States	Addison Gilbert Hospital	Gloucester	Massachusetts
United States	Southeastern Medical Oncology Center-Goldsboro	Goldsboro	North Carolina
United States	Wayne Memorial Hospital	Goldsboro	North Carolina
United States	Aurora Cancer Care-Grafton	Grafton	Wisconsin
United States	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana
United States	Aurora BayCare Medical Center	Green Bay	Wisconsin
United States	Green Bay Oncology at Saint Vincent Hospital	Green Bay	Wisconsin
United States	Green Bay Oncology Limited at Saint Mary's Hospital	Green Bay	Wisconsin
United States	Saint Vincent Hospital Cancer Center at Saint Mary's	Green Bay	Wisconsin
United States	Saint Vincent Hospital Cancer Center Green Bay	Green Bay	Wisconsin
United States	Cone Health Cancer Center	Greensboro	North Carolina
United States	Wayne Hospital	Greenville	Ohio
United States	Medical Oncology and Hematology Group PC-Guilford	Guilford	Connecticut
United States	Kaiser Permanente - Harbor City	Harbor City	California
United States	Smilow Cancer Hospital Care Center at Saint Francis	Hartford	Connecticut
United States	Geisinger Medical Center-Cancer Center Hazleton	Hazleton	Pennsylvania
United States	Saint Peter's Community Hospital	Helena	Montana
United States	21st Century Oncology - Henderson	Henderson	Nevada
United States	Cancer and Blood Specialists-Henderson	Henderson	Nevada
United States	Comprehensive Cancer Centers of Nevada - Henderson	Henderson	Nevada
United States	Comprehensive Cancer Centers of Nevada-Southeast Henderson	Henderson	Nevada
United States	Las Vegas Cancer Center-Henderson	Henderson	Nevada
United States	Hendersonville Hematology and Oncology at Pardee	Hendersonville	North Carolina
United States	Margaret R Pardee Memorial Hospital	Hendersonville	North Carolina
United States	Hinsdale Hematology Oncology Associates Incorporated	Hinsdale	Illinois
United States	Hawaii Cancer Care Inc-Liliha	Honolulu	Hawaii
United States	Hawaii Cancer Care Inc-POB II	Honolulu	Hawaii
United States	Hawaii Oncology Inc-Kuakini	Honolulu	Hawaii
United States	Kaiser Permanente Moanalua Medical Center	Honolulu	Hawaii
United States	Kuakini Medical Center	Honolulu	Hawaii
United States	Queen's Medical Center	Honolulu	Hawaii
United States	Straub Clinic and Hospital	Honolulu	Hawaii
United States	University of Hawaii Cancer Center	Honolulu	Hawaii
United States	Mary Bird Perkins Cancer Center/Terrebonne General Medical Center	Houma	Louisiana
United States	M D Anderson Cancer Center	Houston	Texas
United States	Hutchinson Area Health Care	Hutchinson	Minnesota
United States	Cancer Center of Kansas-Independence	Independence	Kansas
United States	Green Bay Oncology - Iron Mountain	Iron Mountain	Michigan
United States	Kaiser Permanente-Irvine	Irvine	California
United States	Allegiance Health	Jackson	Michigan
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Mayo Clinic in Florida	Jacksonville	Florida
United States	Southeastern Medical Oncology Center-Jacksonville	Jacksonville	North Carolina
United States	Mercy Health System	Janesville	Wisconsin
United States	McFarland Clinic PC-Jefferson	Jefferson	Iowa
United States	Capital Region Medical Center-Goldschmidt Cancer Center	Jefferson City	Missouri
United States	Freeman Health System	Joplin	Missouri
United States	Castle Medical Center	Kailua	Hawaii
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Aurora Cancer Care-Kenosha South	Kenosha	Wisconsin
United States	Kettering Medical Center	Kettering	Ohio
United States	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois
United States	Cancer Center of Kansas-Kingman	Kingman	Kansas
United States	Kinston Medical Specialists PA	Kinston	North Carolina
United States	Fairfield Medical Center	Lancaster	Ohio
United States	Lancaster Radiation Oncology	Lancaster	Ohio
United States	Sparrow Hospital	Lansing	Michigan
United States	21st Century Oncology	Las Vegas	Nevada
United States	21st Century Oncology - Fort Apache	Las Vegas	Nevada
United States	21st Century Oncology - Vegas Tenaya	Las Vegas	Nevada
United States	Cancer and Blood Specialists-Fort Apache	Las Vegas	Nevada
United States	Cancer and Blood Specialists-Shadow	Las Vegas	Nevada
United States	Cancer and Blood Specialists-Tenaya	Las Vegas	Nevada
United States	Cancer Therapy and Integrative Medicine	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada - Central Valley	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada - Northwest	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada-Summerlin	Las Vegas	Nevada
United States	HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills	Las Vegas	Nevada
United States	HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway	Las Vegas	Nevada
United States	HealthCare Partners Medical Group Oncology/Hematology-San Martin	Las Vegas	Nevada
United States	HealthCare Partners Medical Group Oncology/Hematology-Tenaya	Las Vegas	Nevada
United States	Las Vegas Cancer Center-Medical Center	Las Vegas	Nevada
United States	Nevada Cancer Research Foundation CCOP	Las Vegas	Nevada
United States	Radiation Oncology Centers of Nevada Central	Las Vegas	Nevada
United States	Radiation Oncology Centers of Nevada Southeast	Las Vegas	Nevada
United States	University Medical Center of Southern Nevada	Las Vegas	Nevada
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Beebe Medical Center	Lewes	Delaware
United States	Geisinger Medical Oncology-Lewisburg	Lewisburg	Pennsylvania
United States	Central Maine Medical Center	Lewiston	Maine
United States	Lewistown Hospital	Lewistown	Pennsylvania
United States	Cancer Center of Kansas-Liberal	Liberal	Kansas
United States	Wilcox Memorial Hospital and Kauai Medical Clinic	Lihue	Hawaii
United States	Lima Memorial Hospital	Lima	Ohio
United States	Saint Mary Mercy Hospital	Livonia	Michigan
United States	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California
United States	Kaiser Permanente-Cadillac	Los Angeles	California
United States	Los Angeles County-USC Medical Center	Los Angeles	California
United States	USC / Norris Comprehensive Cancer Center	Los Angeles	California
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	Cancer Center of Kansas-Manhattan	Manhattan	Kansas
United States	Holy Family Memorial Hospital	Manitowoc	Wisconsin
United States	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota
United States	Saint John's Hospital - Healtheast	Maplewood	Minnesota
United States	Marietta Memorial Hospital	Marietta	Ohio
United States	Bay Area Medical Center	Marinette	Wisconsin
United States	Vince Lombardi Cancer Clinic-Marinette	Marinette	Wisconsin
United States	OneHealth Marion General Hospital	Marion	Ohio
United States	McFarland Clinic PC-Marshalltown	Marshalltown	Iowa
United States	Marshfield Clinic	Marshfield	Wisconsin
United States	Saint Joseph's Hospital	Marshfield	Wisconsin
United States	Fremont - Rideout Cancer Center	Marysville	California
United States	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois
United States	Toledo Clinic Cancer Centers-Maumee	Maumee	Ohio
United States	Toledo Radiation Oncology at Northwest Ohio Onocolgy Center	Maumee	Ohio
United States	Loyola University Medical Center	Maywood	Illinois
United States	Cancer Center of Kansas - McPherson	McPherson	Kansas
United States	Cone Heath Cancer Center at Mebane	Mebane	North Carolina
United States	Riddle Memorial Hospital	Media	Pennsylvania
United States	Franciscan Saint Anthony Health-Michigan City	Michigan City	Indiana
United States	Woodland Cancer Care Center	Michigan City	Indiana
United States	Orange Regional Medical Center	Middletown	New York
United States	Aurora Cancer Care-Milwaukee	Milwaukee	Wisconsin
United States	Aurora Saint Luke's Medical Center	Milwaukee	Wisconsin
United States	Aurora Sinai Medical Center	Milwaukee	Wisconsin
United States	Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Health Partners Inc	Minneapolis	Minnesota
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin
United States	Community Medical Hospital	Missoula	Montana
United States	Saint Patrick Hospital - Community Hospital	Missoula	Montana
United States	Kaiser Permanente-Modesto	Modesto	California
United States	Memorial Medical Center	Modesto	California
United States	Garneau, Stewart C MD (UIA Investigator)	Moline	Illinois
United States	Porubcin, Michael MD (UIA Investigator)	Moline	Illinois
United States	Spector, David MD (UIA Investigator)	Moline	Illinois
United States	Trinity Medical Center	Moline	Illinois
United States	Illinois CancerCare-Monmouth	Monmouth	Illinois
United States	Mercy Memorial Hospital	Monroe	Michigan
United States	Toledo Clinic Cancer Centers-Monroe	Monroe	Michigan
United States	Good Samaritan Regional Health Center	Mount Vernon	Illinois
United States	Knox Community Hospital	Mount Vernon	Ohio
United States	Palo Alto Medical Foundation-Camino Division	Mountain View	California
United States	Palo Alto Medical Foundation-Gynecologic Oncology	Mountain View	California
United States	ProHealth D N Greenwald Center	Mukwonago	Wisconsin
United States	Yale University	New Haven	Connecticut
United States	Tulane University Health Sciences Center	New Orleans	Louisiana
United States	Cancer Center of Western Wisconsin	New Richmond	Wisconsin
United States	New Ulm Medical Center	New Ulm	Minnesota
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	Christiana Gynecologic Oncology LLC	Newark	Delaware
United States	Delaware Clinical and Laboratory Physicians PA	Newark	Delaware
United States	Helen F Graham Cancer Center	Newark	Delaware
United States	Licking Memorial Hospital	Newark	Ohio
United States	Medical Oncology Hematology Consultants PA	Newark	Delaware
United States	Newark Radiation Oncology	Newark	Ohio
United States	Regional Hematology and Oncology PA	Newark	Delaware
United States	USC Norris Oncology/Hematology-Newport Beach	Newport Beach	California
United States	Cancer Center of Kansas - Newton	Newton	Kansas
United States	Community Cancer Center Foundation	Normal	Illinois
United States	Yale-New Haven Hospital North Haven Medical Center	North Haven	Connecticut
United States	Sutter Cancer Research Consortium	Novato	California
United States	Kaiser Permanente-Oakland	Oakland	California
United States	ProHealth Oconomowoc Memorial Hospital	Oconomowoc	Wisconsin
United States	Green Bay Oncology - Oconto Falls	Oconto Falls	Wisconsin
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Smilow Cancer Hospital-Orange Care Center	Orange	Connecticut
United States	UC Irvine Health/Chao Family Comprehensive Cancer Center	Orange	California
United States	Saint Charles Hospital	Oregon	Ohio
United States	Toledo Clinic Cancer Centers-Oregon	Oregon	Ohio
United States	Florida Hospital Orlando	Orlando	Florida
United States	Vince Lombardi Cancer Clinic - Oshkosh	Oshkosh	Wisconsin
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	Radiation Oncology of Northern Illinois	Ottawa	Illinois
United States	Palo Alto Medical Foundation Health Care	Palo Alto	California
United States	Kaiser Permanente - Panorama City	Panorama City	California
United States	Paoli Memorial Hospital	Paoli	Pennsylvania
United States	Cancer Center of Kansas - Parsons	Parsons	Kansas
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center	Pekin	Illinois
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	OSF Saint Francis Medical Center	Peoria	Illinois
United States	OSF Saint Francis Radiation Oncology at Peoria Cancer Center	Peoria	Illinois
United States	Illinois CancerCare-Peru	Peru	Illinois
United States	Valley Radiation Oncology	Peru	Illinois
United States	University of Pennsylvania/Abramson Cancer Center	Philadelphia	Pennsylvania
United States	Saint Joseph Mercy Oakland	Pontiac	Michigan
United States	Lake Huron Medical Center	Port Huron	Michigan
United States	Southern Ohio Medical Center	Portsmouth	Ohio
United States	Kootenai Cancer Center	Post Falls	Idaho
United States	Geisinger Medical Oncology-Pottsville	Pottsville	Pennsylvania
United States	Cancer Center of Kansas - Pratt	Pratt	Kansas
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Aurora Cancer Care-Racine	Racine	Wisconsin
United States	Rapid City Regional Hospital	Rapid City	South Dakota
United States	Penn State Health Saint Joseph Medical Center	Reading	Pennsylvania
United States	Kaiser Permanente-Redwood City	Redwood City	California
United States	Beebe Health Campus	Rehoboth Beach	Delaware
United States	Annie Penn Memorial Hospital	Reidsville	North Carolina
United States	Marshfield Clinic at James Beck Cancer Center	Rhinelander	Wisconsin
United States	Saint Mary's Hospital	Rhinelander	Wisconsin
United States	Lakeview Medical Center-Marshfield Clinic	Rice Lake	Wisconsin
United States	Marshfield Clinic-Rice Lake Center	Rice Lake	Wisconsin
United States	Kaiser Permanente-Richmond	Richmond	California
United States	Reid Health	Richmond	Indiana
United States	Kaiser Permanente-Riverside	Riverside	California
United States	North Memorial Medical Health Center	Robbinsdale	Minnesota
United States	Mayo Clinic	Rochester	Minnesota
United States	SwedishAmerican Regional Cancer Center/ACT	Rockford	Illinois
United States	Penobscot Bay Medical Center	Rockport	Maine
United States	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri
United States	Saint John's Clinic-Rolla-Cancer and Hematology	Rolla	Missouri
United States	Kaiser Permanente-Roseville	Roseville	California
United States	Sutter Cancer Centers Radiation Oncology Services-Roseville	Roseville	California
United States	Sutter Roseville Medical Center	Roseville	California
United States	Kaiser Permanente - Sacramento	Sacramento	California
United States	Kaiser Permanente-South Sacramento	Sacramento	California
United States	Sutter General Hospital	Sacramento	California
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California
United States	Saint Mary's of Michigan	Saginaw	Michigan
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Saint Louis Cancer and Breast Institute-South City	Saint Louis	Missouri
United States	Metro Minnesota Community Oncology Research Consortium	Saint Louis Park	Minnesota
United States	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota
United States	Regions Hospital	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Sainte Genevieve County Memorial Hospital	Sainte Genevieve	Missouri
United States	Cancer Center of Kansas - Salina	Salina	Kansas
United States	Peninsula Regional Medical Center	Salisbury	Maryland
United States	Kaiser Permanente-San Diego Mission	San Diego	California
United States	Kaiser Permanente-San Diego Zion	San Diego	California
United States	California Pacific Medical Center-Pacific Campus	San Francisco	California
United States	Kaiser Permanente-San Francisco	San Francisco	California
United States	Kaiser Permanente-Santa Teresa-San Jose	San Jose	California
United States	Kaiser Permanente San Leandro	San Leandro	California
United States	Kaiser Permanente-San Marcos	San Marcos	California
United States	Kaiser Permanente-San Rafael	San Rafael	California
United States	Kootenai Cancer Clinic	Sandpoint	Idaho
United States	Kaiser Permanente Medical Center - Santa Clara	Santa Clara	California
United States	Palo Alto Medical Foundation-Santa Cruz	Santa Cruz	California
United States	Kaiser Permanente-Santa Rosa	Santa Rosa	California
United States	Sutter Pacific Medical Foundation	Santa Rosa	California
United States	Lewis Cancer and Research Pavilion at Saint Joseph's/Candler	Savannah	Georgia
United States	Nanticoke Memorial Hospital	Seaford	Delaware
United States	Pacific Medical Center-First Hill	Seattle	Washington
United States	Virginia Mason Medical Center	Seattle	Washington
United States	Grand View Hospital	Sellersville	Pennsylvania
United States	Saint Francis Regional Medical Center	Shakopee	Minnesota
United States	HSHS Saint Nicholas Hospital	Sheboygan	Wisconsin
United States	Vince Lombardi Cancer Clinic-Sheboygan	Sheboygan	Wisconsin
United States	Welch Cancer Center	Sheridan	Wyoming
United States	Mercy Medical Center-Sioux City	Sioux City	Iowa
United States	Saint Luke's Regional Medical Center	Sioux City	Iowa
United States	Siouxland Regional Cancer Center	Sioux City	Iowa
United States	Sanford Cancer Center-Oncology Clinic	Sioux Falls	South Dakota
United States	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota
United States	Kaiser Permanente-South San Francisco	South San Francisco	California
United States	Providence Hospital-Southfield Cancer Center	Southfield	Michigan
United States	Cancer Research for the Ozarks NCORP	Springfield	Missouri
United States	Central Illinois Hematology Oncology Center	Springfield	Illinois
United States	CoxHealth South Hospital	Springfield	Missouri
United States	Memorial Medical Center	Springfield	Illinois
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	Springfield Clinic	Springfield	Illinois
United States	Springfield Regional Cancer Center	Springfield	Ohio
United States	Springfield Regional Medical Center	Springfield	Ohio
United States	Geisinger Medical Group	State College	Pennsylvania
United States	Iredell Memorial Hospital	Statesville	North Carolina
United States	Marshfield Clinic Cancer Care at Saint Michael's Hospital	Stevens Point	Wisconsin
United States	Saint Michael's Hospital	Stevens Point	Wisconsin
United States	Lakeview Hospital	Stillwater	Minnesota
United States	Kaiser Permanente-Stockton	Stockton	California
United States	Green Bay Oncology - Sturgeon Bay	Sturgeon Bay	Wisconsin
United States	Missouri Baptist Sullivan Hospital	Sullivan	Missouri
United States	Aurora Medical Center in Summit	Summit	Wisconsin
United States	Palo Alto Medical Foundation-Sunnyvale	Sunnyvale	California
United States	Missouri Baptist Outpatient Center-Sunset Hills	Sunset Hills	Missouri
United States	Cancer Care Specialists of Illinois-Swansea	Swansea	Illinois
United States	Flower Hospital	Sylvania	Ohio
United States	Mercy Hospital of Tiffin	Tiffin	Ohio
United States	Mercy Saint Anne Hospital	Toledo	Ohio
United States	Saint Vincent Mercy Medical Center	Toledo	Ohio
United States	The Toledo Hospital/Toledo Children's Hospital	Toledo	Ohio
United States	Toledo Clinic Cancer Centers-Toledo	Toledo	Ohio
United States	Toledo Community Hospital Oncology Program CCOP	Toledo	Ohio
United States	University of Toledo	Toledo	Ohio
United States	Charlotte Hungerford Hospital Center for Cancer Care	Torrington	Connecticut
United States	Upper Valley Medical Center	Troy	Ohio
United States	Gene Upshaw Memorial Tahoe Forest Cancer Center	Truckee	California
United States	Smilow Cancer Hospital Care Center-Trumbull	Trumbull	Connecticut
United States	The University of Arizona Medical Center-University Campus	Tucson	Arizona
United States	University of Arizona Cancer Center-North Campus	Tucson	Arizona
United States	Vince Lombardi Cancer Clinic-Two Rivers	Two Rivers	Wisconsin
United States	Carle Cancer Center	Urbana	Illinois
United States	The Carle Foundation Hospital	Urbana	Illinois
United States	Kaiser Permanente Medical Center-Vacaville	Vacaville	California
United States	Sutter Cancer Centers Radiation Oncology Services-Vacaville	Vacaville	California
United States	Kaiser Permanente-Vallejo	Vallejo	California
United States	Sutter Solano Medical Center/Cancer Center	Vallejo	California
United States	Inspira Medical Center Vineland	Vineland	New Jersey
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	John Muir Medical Center-Walnut Creek	Walnut Creek	California
United States	Kaiser Permanente-Walnut Creek	Walnut Creek	California
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
United States	MedStar Georgetown University Hospital	Washington	District of Columbia
United States	MedStar Washington Hospital Center	Washington	District of Columbia
United States	Smilow Cancer Hospital-Waterbury Care Center	Waterbury	Connecticut
United States	Aurora Cancer Care-Waukesha	Waukesha	Wisconsin
United States	ProHealth Waukesha Memorial Hospital	Waukesha	Wisconsin
United States	UW Cancer Center at ProHealth Care	Waukesha	Wisconsin
United States	Marshfield Clinic-Wausau Center	Wausau	Wisconsin
United States	Fulton County Health Center	Wauseon	Ohio
United States	Aurora Cancer Care-Milwaukee West	Wauwatosa	Wisconsin
United States	Cancer Center of Kansas - Wellington	Wellington	Kansas
United States	Aurora West Allis Medical Center	West Allis	Wisconsin
United States	Mercy Medical Center-West Lakes	West Des Moines	Iowa
United States	Methodist West Hospital	West Des Moines	Iowa
United States	Reading Hospital	West Reading	Pennsylvania
United States	Saint Ann's Hospital	Westerville	Ohio
United States	Marshfield Clinic - Weston Center	Weston	Wisconsin
United States	Saint Clare's Hospital	Weston	Wisconsin
United States	Associates In Womens Health	Wichita	Kansas
United States	Cancer Center of Kansas - Wichita	Wichita	Kansas
United States	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas
United States	Via Christi Regional Medical Center	Wichita	Kansas
United States	Wichita NCI Community Oncology Research Program	Wichita	Kansas
United States	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania
United States	Rice Memorial Hospital	Willmar	Minnesota
United States	Christiana Care Health System-Wilmington Hospital	Wilmington	Delaware
United States	Southeastern Medical Oncology Center-Wilson	Wilson	North Carolina
United States	Cancer Center of Kansas - Winfield	Winfield	Kansas
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	Marshfield Clinic - Wisconsin Rapids Center	Wisconsin Rapids	Wisconsin
United States	Inspira Medical Center Woodbury	Woodbury	New Jersey
United States	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota
United States	Kaiser Permanente	Woodland Hills	California
United States	Wright-Patterson Medical Center	Wright-Patterson Air Force Base	Ohio
United States	Lankenau Medical Center	Wynnewood	Pennsylvania
United States	Main Line Health NCORP	Wynnewood	Pennsylvania
United States	Rush-Copley Healthcare Center	Yorkville	Illinois
United States	Genesis Healthcare System Cancer Care Center	Zanesville	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Southwest Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Gene Expression Profiles	Bone marrow compared to that of an aspirate taken at the site of the EMP. Data will be log-transformed before analysis. Exploratory analyses will examine underlying distributions using boxplots, density plots, scatter plots, etc. For differential expression analysis of the two sample types t-tests will be conducted on genes. False discovery rate will be used to control the average false positive proportions among selected genes. Genes will be ranked by their q-value and pathway analysis conducted upon selected genes to determine biological plausibility and relevance to molecular functionality.	Up to 3 years
Other	Incidence of CR by PET, Defined as the Disappearance of All Focal Lesions and the Resolution of EMD	Univariate and multivariate logistic regression will be used to determine the impact of biochemical CR on CR by PET. In the multivariate analysis adjustment for standard prognostic factors such as age, albumin, beta-2 microglobulin, serum creatinine, c-reactive protein and lactate dehydrogenase will be included.	Up to week 45
Primary	Progression-free Survival	Assessed in each arm using the method of Kaplan Meier and compared between arms using the stratified long-rank test. Progression is defined using the International Uniform Response Criteria for Multiple Myeloma as new or increase in size of existing bone lesions or soft tissue plasmacytomas; or development of hypercalcemia attributable solely to MM; or = 25% increase from baseline or lowest response level of either serum M protein, urine M protein, difference in involved & uninvolved serum free light chain level or bone marrow plasma cell percentage.	From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause, assessed up to 2 years
Secondary	Overall Survival	Assessed in each arm using the method of Kaplan Meier and compared between arms using the stratified log-rank test.	From date of registration to date of death due to any cause, assessed up to 3 years
Secondary	Best Overall Response - Partial Response (PR), Very Good Partial Response (VGPR), Unconfirmed PR (uPR), Stable Disease (SD) Progression (PROG)	Per International Uniform Response Criteria for Multiple Myeloma PR- = 50% reduction in size of soft tissue plasmacytomas & plasma cells; = 50% decrease in serum & reduction in urine M protein = 90% or to < 200 mg/24hr or = 50% decrease in difference in uninvolved & involved serum free light chain levels; VGPR- PR + Serum and urine M proteins detectable by immunofixation but not on electrophoresis or = 90% reduction in serum M protein & urine M protein < 100 mg/24 hrs; uPR- 1 objective status of PR, but confirmation studies are not done, or do not meet the requirements necessary to confirm response; SD- does not meet criteria for sCR, CR, VGPR, PR or PROG; PROG- new or increase in size of existing bone lesions or soft tissue plasmacytomas/ development of hypercalcemia attributable solely to MM/ = 25% increase from baseline/ lowest response level of either serum or Urine M protein, difference in involved & uninvolved serum free light chain level or bone marrow plasma cell percentage.	From date of registration to date of best response while on study treatment
Secondary	Progression-free Survival of Crossover Group	Assessed in the crossover arm using the method of Kaplan Meier. Progression is defined using the International Uniform Response Criteria for Multiple Myeloma as new or increase in size of existing bone lesions or soft tissue plasmacytomas; or development of hypercalcemia attributable solely to MM; or = 25% increase from baseline or lowest response level of either serum M protein, urine M protein, difference in involved & uninvolved serum free light chain level or bone marrow plasma cell percentage.	From date of crossover to date of subsequent documentation of progression or symptomatic deterioration, or death due to any cause, assessed up to 3 years from randomization
Secondary	Overall Survival Crossover Group	Assessed in the crossover arm using the method of Kaplan Meier.	From date of crossover to date of death due to any cause, assessed up to 3 years from randomization