Lenalidomide, and Dexamethasone With or Without Daratumumab in Treating Patients With High-Risk Smoldering Myeloma

Smoldering Plasma Cell Myeloma Clinical Trial

Official title:

Daratumumab to Enhance Therapeutic Effectiveness of Revlimid in Smoldering Myeloma (DETER-SMM)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03937635
• Other study ID #: EAA173
• Secondary ID: NCI-2018-02611EA
• Status: Recruiting
• Phase: Phase 3
• Start date: September 16, 2019
• Est. completion date: December 31, 2029

Study information

• Verified date: June 2023
• Source: Eastern Cooperative Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase III trial studies how well lenalidomide and dexamethasone works with or without daratumumab in treating patients with high-risk smoldering myeloma. Drugs used in chemotherapy, such as lenalidomide and dexamethasone, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as daratumumab, may induce changes in the body's immune system and may interfere with the ability of tumor cells to grow and spread. Giving lenalidomide and dexamethasone with daratumumab may work better in treating patients with smoldering myeloma.

Description:

PRIMARY OBJECTIVES: I. To compare overall survival in patients with high-risk smoldering multiple myeloma randomized to daratumumab-lenalidomide (revlimid)-dexamethasone or revlimid-dexamethasone. SECONDARY OBJECTIVES: I. To compare progression-free survival and response rates between arms. II. To evaluate safety and compare toxicity rates between arms. III. To monitor incidence of infusion-related reactions over the first cycle of daratumumab. IV. To evaluate stem cell mobilization failure and early stem cell mobilization feasibility. EXPLORATORY OBJECTIVES: I. To measure treatment exposure and adherence. II. To estimate treatment duration and time to progression. PATIENT-REPORTED OUTCOMES OBJECTIVES: I. To compare change in health-related quality of life (Functional Assessment of Cancer Therapy [FACT]- General [G]]) from baseline to end of study therapy between arms. II. To compare change in FACT-G scores from treatment end to 6-months post-treatment end between arms. III. To describe changes in FACT-G scores over study therapy and shortly after treatment discontinuation and evaluate correlation with survival. IV. To evaluate attributes of select patient reported treatment-emergent symptomatic adverse events (Patient Reported Outcomes [PRO]-Common Terminology Criteria for Adverse Events [CTCAE]) longitudinally. V. To derive an overall PRO-CTCAE score at each assessment time point. VI. To measure the likelihood of medication adherence (ASK-12) at 6 month intervals throughout treatment. VII. To assess the association of overall PRO-CTCAE score with FACT-G score. VIII. To compare select PRO-CTCAE items and related provider-reported CTCAEs. IX. To evaluate association between treatment adherence and Adherence Starts with Knowledge 12 (ASK-12) score. X. To assess correlation of treatment adherence and ASK-12 score with FACT-G score. XI. To tabulate PRO compliance and completion rates. LABORATORY OBJECTIVES: I. To compare minimal residual disease negative rate after 12 cycles of study therapy between arms. II. To compare minimal residual disease (MRD) positive to negative conversion rates from 12 cycles to end of treatment between arms. III. To examine patterns of change in minimal residual disease levels during study therapy. IV. To evaluate agreement and discordance between methods determining disease-free status. V. To assess the prognostic value of minimal residual disease status at 12 cycles for overall and progression-free survival. IMAGING OBJECTIVES: I. To evaluate the association of baseline fludeoxyglucose F-18 (FDG)-positron emission tomography (PET)/computed tomography (CT) imaging with progression-free survival. II. To assess the ability of baseline FDG-PET/CT to predict minimal residual disease status after 12 cycles of study therapy and at the end of study therapy. III. To describe the results of subsequent FDG-PET/CT imaging studies in the subset of patients with baseline abnormal FDG-PET/CT, and to associate these results with progression-free survival (PFS). OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive daratumumab intravenously (IV) on days 1, 8, 15, and 22 of courses 1-2, days 1 and 15 of courses 3-6, and day 1 of courses 7-24. Patients also receive lenalidomide orally (PO) daily on days 1-21 and dexamethasone PO on days 1, 8, 15, and 22 in courses 1-12. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive lenalidomide PO daily on days 1-21 and dexamethasone PO on days 1, 8, 15, and 22 of courses 1-12. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity. After completion of study, patients will be followed up every 3, 6 or 12 months for up to 15 years from study entry.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 288
• Est. completion date: December 31, 2029
• Est. primary completion date: December 31, 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients must be diagnosed with asymptomatic high-risk smoldering multiple myeloma (SMM) within the past 12 months. High-risk is defined by the presence of 2 or more of

the following factors:

• Abnormal serum free light chain ratio of involved to uninvolved >20, but less than 100 if the involved FLC is >= 10 mg/dL by serum free light chain (FLC) assay
• Serum M-protein level >= 2 gm/dL
• Presence of t(4;14) or del 17p, del 13q or 1q gain by conventional cytogenetics or fluorescence in situ hybridization (FISH) studies.
• >20% plasma cells on biopsy or aspirate
• Bone marrow aspirate and/or biopsy is required to be performed within 42 days prior to randomization and must demonstrate 10-59% clonal plasma cells.
• >= 1 g/dL on serum protein electrophoresis (within 28 days prior to randomization).
• >= 200 mg of monoclonal protein on a 24 hour urine protein electrophoresis (within 28 days prior to randomization).
• NOTE: In the rare situation where the serum protein electrophoresis (SPEP) is felt to be unreliable, then quantitative immunoglobulin levels on nephelometry or turbidometry can be accepted.
• SPEP, urine protein electrophoresis (UPEP), and serum FLC are required to be performed within 28 days prior to randomization.
• NOTE: UPEP (on a 24-hour collection) is required; no substitute method is acceptable. Urine must be followed monthly if the baseline urine M-spike is >= 200 mg/24 hour (hr), and urine in addition to serum must be followed in order to confirm a very good partial response (VGPR) or higher response.
• Patients must have no lytic lesions, no known plasmacytoma, and no unexplained hypercalcemia (i.e., > 11 mg/dL or 1mg/dL above upper limit of normal [ULN]).
• Hemoglobin >= 11 g/dL (within 28 days prior to randomization).
• Platelet count >= 100,000 cells/mm^3 (within 28 days prior to randomization).
• Absolute neutrophil count >= 1500 cells/mm^3 (within 28 days prior to randomization).
• Calculated creatinine clearance >= 30 mL/min (within 28 days prior to randomization).
• Bilirubin =< 1.5 mg/dL (within 28 days prior to randomization).
• 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 (within 28 days prior to randomization).
• Patients must not have any prior or concurrent systemic or radiation therapy for the treatment of myeloma. Patients must also not have contraindication to deep vein thrombosis (DVT) prophylaxis/aspirin.
• Patients must not have more than one focal marrow lesion on magnetic resonance imaging (MRI) of either pelvis or spine. Patients with indwelling pacemakers and/or ICD (implantable cardioverter-defibrillator) that is known or suspected to be MRI incompatible will be excused from this test.
• Concurrent use of erythropoietin is not allowed while on study therapy.
• Prior or glucocorticosteroid therapy for the treatment of multiple myeloma is not permitted. Prior systemic glucocorticosteroid use for the treatment of non-malignant disorders is permitted; concurrent use after registration on the study should be restricted to the equivalent of prednisone 10 mg per day. Prior or concurrent topical or localized glucocorticosteroid therapy to treat non-malignant comorbid disorders is permitted.
• Patients must not have active, uncontrolled seizure disorder. Patients must not have had a seizure in the last 6 months.
• Patients must not have uncontrolled intercurrent illness including uncontrolled hypertension, symptomatic congestive heart failure, unstable angina, uncontrolled cardiac arrhythmia, uncontrolled psychiatric illness or social situation that would limit compliance with the study, or a prior history of Stevens Johnson syndrome.
• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2.
• Patients with monoclonal gammopathy of undetermined significance are not eligible.
• Patients must not have grade 2 or higher peripheral neuropathy per CTCAE.
• Patients must not have active, uncontrolled infection.
• Patients may have a history of current or previous deep vein thrombosis or pulmonary embolism but are required to take some form of anti-coagulation as prophylaxis if they are not currently on full-dose anticoagulation.
• Patients should not have New York Heart Association classification III or IV heart failure at baseline.
• Patients with a history of prior malignancy are eligible provided they were treated with curative intent and have been free of disease for the time period considered appropriate for cure of the specific cancer. For most diseases this time frame is 5 years.
• Patients must agree to register into the mandatory Risk Evaluation and Mitigation Strategy (REMS) program and be willing and able to comply with the requirements of REMS.
• Women must not be pregnant due to potential harm to the fetus from daratumumab and lenalidomide. All females of childbearing potential (FCBP) must have a blood test or urine study with a sensitivity of at least 25 mIU/mL within 10-14 days prior to the first dose of lenalidomide and again within 24 hours prior to the first dose of lenalidomide. FCBP must also agree to ongoing pregnancy testing while on treatment. A female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy, or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
• Females of childbearing potential (FCBP) must either abstain from sexual intercourse for the duration of their participation in the study or agree to use TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME for 1) at least 28 days before starting study treatment; 2) while participating in the study; 3) during dose interruptions; and 4) for at least 28 days after the last dose of protocol treatment (FCBP who are assigned to Arm A and receive daratumumab must extend this contraception requirement to 3 months after the last dose of protocol treatment). Women must also agree to not breastfeed during this same time period. Men must agree to either abstain from sexual intercourse for the duration of their participation in the study or use a latex condom during sexual contact with a FCBP while participating in the study and for 28 days after the last dose of protocol treatment even if they have had a successful vasectomy. Men must also agree to abstain from donating sperm while on study treatment and for 28 days after the last dose of protocol treatment even if they have had a successful vasectomy. Both women and men must both agree to abstain from donating blood during study participation and for at least 28 days after the last dose of protocol treatment.
• Human immunodeficiency virus (HIV)+ patients with undetectable HIV viral loads tested within 6 months are eligible.
• Patients should not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to daratumumab, lenalidomide, or dexamethasone.
• Patients must not have known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) <50% of predicted normal or known moderate or severe persistent asthma within 2 years prior to randomization

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Smoldering Multiple Myeloma
• Smoldering Plasma Cell Myeloma

Intervention

Biological:
• Daratumumab
Given IV

Drug:
• Dexamethasone
Given PO
• Lenalidomide
Given PO

Other:
• Quality-of-Life Assessment
Ancillary studies
• Questionnaire Administration
Ancillary studies

Locations

Country	Name	City	State
United States	Providence Regional Cancer System-Aberdeen	Aberdeen	Washington
United States	Hickman Cancer Center	Adrian	Michigan
United States	Riverwood Healthcare Center	Aitkin	Minnesota
United States	Mayo Clinic Health System in Albert Lea	Albert Lea	Minnesota
United States	Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania
United States	American Fork Hospital / Huntsman Intermountain Cancer Center	American Fork	Utah
United States	Mary Greeley Medical Center	Ames	Iowa
United States	McFarland Clinic PC - Ames	Ames	Iowa
United States	Community Hospital of Anaconda	Anaconda	Montana
United States	Alaska Breast Care and Surgery LLC	Anchorage	Alaska
United States	Alaska Oncology and Hematology LLC	Anchorage	Alaska
United States	Alaska Women's Cancer Care	Anchorage	Alaska
United States	Anchorage Associates in Radiation Medicine	Anchorage	Alaska
United States	Anchorage Oncology Centre	Anchorage	Alaska
United States	Anchorage Radiation Therapy Center	Anchorage	Alaska
United States	Katmai Oncology Group	Anchorage	Alaska
United States	Providence Alaska Medical Center	Anchorage	Alaska
United States	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	ThedaCare Regional Cancer Center	Appleton	Wisconsin
United States	Mission Hope Medical Oncology - Arroyo Grande	Arroyo Grande	California
United States	PCR Oncology	Arroyo Grande	California
United States	Duluth Clinic Ashland	Ashland	Wisconsin
United States	Northwest Wisconsin Cancer Center	Ashland	Wisconsin
United States	Emory Saint Joseph's Hospital	Atlanta	Georgia
United States	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia
United States	MultiCare Auburn Medical Center	Auburn	Washington
United States	Rocky Mountain Cancer Centers-Aurora	Aurora	Colorado
United States	Rush - Copley Medical Center	Aurora	Illinois
United States	The Medical Center of Aurora	Aurora	Colorado
United States	Saint Alphonsus Medical Center-Baker City	Baker City	Oregon
United States	Saint Louis Cancer and Breast Institute-Ballwin	Ballwin	Missouri
United States	Saint Agnes Hospital	Baltimore	Maryland
United States	Flaget Memorial Hospital	Bardstown	Kentucky
United States	Hematology/Oncology Clinic PLLC	Baton Rouge	Louisiana
United States	Bronson Battle Creek	Battle Creek	Michigan
United States	Indu and Raj Soin Medical Center	Beavercreek	Ohio
United States	Overlake Medical Center	Bellevue	Washington
United States	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington
United States	Strecker Cancer Center-Belpre	Belpre	Ohio
United States	Saint Charles Health System	Bend	Oregon
United States	Lehigh Valley Hospital - Muhlenberg	Bethlehem	Pennsylvania
United States	Billings Clinic Cancer Center	Billings	Montana
United States	Saint Vincent Frontier Cancer Center	Billings	Montana
United States	Saint Vincent Healthcare	Billings	Montana
United States	Saint Elizabeth Boardman Hospital	Boardman	Ohio
United States	Prisma Health Cancer Institute - Spartanburg	Boiling Springs	South Carolina
United States	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho
United States	Saint Luke's Cancer Institute - Boise	Boise	Idaho
United States	Central Care Cancer Center - Bolivar	Bolivar	Missouri
United States	McFarland Clinic PC-Boone	Boone	Iowa
United States	Tufts Medical Center	Boston	Massachusetts
United States	Boulder Community Hospital	Boulder	Colorado
United States	Rocky Mountain Cancer Centers-Boulder	Boulder	Colorado
United States	Bozeman Deaconess Hospital	Bozeman	Montana
United States	Essentia Health Saint Joseph's Medical Center	Brainerd	Minnesota
United States	Cox Cancer Center Branson	Branson	Missouri
United States	Harrison HealthPartners Hematology and Oncology-Bremerton	Bremerton	Washington
United States	Harrison Medical Center	Bremerton	Washington
United States	United Hospital Center	Bridgeport	West Virginia
United States	IHA Hematology Oncology Consultants-Brighton	Brighton	Michigan
United States	Saint Joseph Mercy Brighton	Brighton	Michigan
United States	Henry Ford Cancer Institute-Downriver	Brownstown	Michigan
United States	Saint Joseph Regional Cancer Center	Bryan	Texas
United States	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California
United States	Highline Medical Center-Main Campus	Burien	Washington
United States	Aurora Cancer Care-Southern Lakes VLCC	Burlington	Wisconsin
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Minnesota Oncology - Burnsville	Burnsville	Minnesota
United States	Loyola Center for Health at Burr Ridge	Burr Ridge	Illinois
United States	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana
United States	Saint Alphonsus Cancer Care Center-Caldwell	Caldwell	Idaho
United States	Cambridge Medical Center	Cambridge	Minnesota
United States	IHA Hematology Oncology Consultants-Canton	Canton	Michigan
United States	Saint Joseph Mercy Canton	Canton	Michigan
United States	Caro Cancer Center	Caro	Michigan
United States	Saint Anthony Regional Hospital	Carroll	Iowa
United States	Carson Tahoe Regional Medical Center	Carson City	Nevada
United States	Sandra L Maxwell Cancer Center	Cedar City	Utah
United States	Rocky Mountain Cancer Centers - Centennial	Centennial	Colorado
United States	Dayton Physicians LLC-Miami Valley South	Centerville	Ohio
United States	Miami Valley Hospital South	Centerville	Ohio
United States	Providence Regional Cancer System-Centralia	Centralia	Washington
United States	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	Geauga Hospital	Chardon	Ohio
United States	Medical University of South Carolina	Charleston	South Carolina
United States	West Virginia University Charleston Division	Charleston	West Virginia
United States	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina
United States	University of Virginia Cancer Center	Charlottesville	Virginia
United States	IHA Hematology Oncology Consultants-Chelsea	Chelsea	Michigan
United States	Saint Joseph Mercy Chelsea	Chelsea	Michigan
United States	Cheyenne Regional Medical Center-West	Cheyenne	Wyoming
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	Bethesda North Hospital	Cincinnati	Ohio
United States	Good Samaritan Hospital - Cincinnati	Cincinnati	Ohio
United States	Oncology Hematology Care Inc-Kenwood	Cincinnati	Ohio
United States	TriHealth Cancer Institute-Anderson	Cincinnati	Ohio
United States	TriHealth Cancer Institute-Westside	Cincinnati	Ohio
United States	Clackamas Radiation Oncology Center	Clackamas	Oregon
United States	Providence Cancer Institute Clackamas Clinic	Clackamas	Oregon
United States	Hematology Oncology Consultants-Clarkston	Clarkston	Michigan
United States	Newland Medical Associates-Clarkston	Clarkston	Michigan
United States	Case Western Reserve University	Cleveland	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	Henry Ford Macomb Hospital-Clinton Township	Clinton Township	Michigan
United States	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa
United States	Mercy Cancer Center-West Lakes	Clive	Iowa
United States	Billings Clinic-Cody	Cody	Wyoming
United States	Kootenai Health - Coeur d'Alene	Coeur d'Alene	Idaho
United States	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	Rocky Mountain Cancer Centers-Penrose	Colorado Springs	Colorado
United States	Saint Francis Cancer Center	Colorado Springs	Colorado
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	Mercy Hospital	Coon Rapids	Minnesota
United States	Bay Area Hospital	Coos Bay	Oregon
United States	Commonwealth Cancer Center-Corbin	Corbin	Kentucky
United States	Alegent Health Mercy Hospital	Council Bluffs	Iowa
United States	Greater Regional Medical Center	Creston	Iowa
United States	Siteman Cancer Center at West County Hospital	Creve Coeur	Missouri
United States	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas
United States	Carle on Vermilion	Danville	Illinois
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Dayton Physician LLC-Miami Valley Hospital North	Dayton	Ohio
United States	Dayton Veterans Affairs Medical Center	Dayton	Ohio
United States	Good Samaritan Hospital - Dayton	Dayton	Ohio
United States	Miami Valley Hospital	Dayton	Ohio
United States	Miami Valley Hospital North	Dayton	Ohio
United States	Henry Ford Medical Center-Fairlane	Dearborn	Michigan
United States	Essentia Health - Deer River Clinic	Deer River	Minnesota
United States	Northwestern Medicine Cancer Center Kishwaukee	DeKalb	Illinois
United States	Delaware Health Center-Grady Cancer Center	Delaware	Ohio
United States	Grady Memorial Hospital	Delaware	Ohio
United States	Cancer Center of Colorado at Sloan's Lake	Denver	Colorado
United States	Colorado Blood Cancer Institute	Denver	Colorado
United States	National Jewish Health-Main Campus	Denver	Colorado
United States	Porter Adventist Hospital	Denver	Colorado
United States	Presbyterian - Saint Lukes Medical Center - Health One	Denver	Colorado
United States	Rocky Mountain Cancer Centers-Midtown	Denver	Colorado
United States	Rocky Mountain Cancer Centers-Rose	Denver	Colorado
United States	Rose Medical Center	Denver	Colorado
United States	SCL Health Saint Joseph Hospital	Denver	Colorado
United States	The Women's Imaging Center	Denver	Colorado
United States	Western Surgical Care	Denver	Colorado
United States	Smilow Cancer Hospital-Derby Care Center	Derby	Connecticut
United States	Broadlawns Medical Center	Des Moines	Iowa
United States	Iowa Lutheran Hospital	Des Moines	Iowa
United States	Iowa Methodist Medical Center	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	Ascension Saint John Hospital	Detroit	Michigan
United States	Henry Ford Hospital	Detroit	Michigan
United States	Essentia Health Saint Mary's - Detroit Lakes Clinic	Detroit Lakes	Minnesota
United States	Dublin Methodist Hospital	Dublin	Ohio
United States	Epic Care-Dublin	Dublin	California
United States	Essentia Health Cancer Center	Duluth	Minnesota
United States	Essentia Health Saint Mary's Medical Center	Duluth	Minnesota
United States	Miller-Dwan Hospital	Duluth	Minnesota
United States	Mercy Medical Center	Durango	Colorado
United States	Southwest Oncology PC	Durango	Colorado
United States	Prisma Health Cancer Institute - Easley	Easley	South Carolina
United States	Great Lakes Cancer Management Specialists-Doctors Park	East China Township	Michigan
United States	Pocono Medical Center	East Stroudsburg	Pennsylvania
United States	Marshfield Medical Center-EC Cancer Center	Eau Claire	Wisconsin
United States	Mayo Clinic Health System-Eau Claire Clinic	Eau Claire	Wisconsin
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Swedish Cancer Institute-Edmonds	Edmonds	Washington
United States	Carle Physician Group-Effingham	Effingham	Illinois
United States	Bay Area Breast Surgeons Inc	Emeryville	California
United States	Epic Care Partners in Cancer Care	Emeryville	California
United States	Walter Knox Memorial Hospital	Emmett	Idaho
United States	Mountain Blue Cancer Care Center - Swedish	Englewood	Colorado
United States	Swedish Medical Center	Englewood	Colorado
United States	The Melanoma and Skin Cancer Institute	Englewood	Colorado
United States	Saint Elizabeth Hospital	Enumclaw	Washington
United States	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois
United States	Providence Regional Cancer Partnership	Everett	Washington
United States	Fairbanks Memorial Hospital	Fairbanks	Alaska
United States	Smilow Cancer Hospital Care Center-Fairfield	Fairfield	Connecticut
United States	Essentia Health Cancer Center-South University Clinic	Fargo	North Dakota
United States	Saint Francis Hospital	Federal Way	Washington
United States	Lake Region Healthcare Corporation-Cancer Care	Fergus Falls	Minnesota
United States	Armes Family Cancer Center	Findlay	Ohio
United States	Blanchard Valley Hospital	Findlay	Ohio
United States	Orion Cancer Care	Findlay	Ohio
United States	Genesee Cancer and Blood Disease Treatment Center	Flint	Michigan
United States	Genesee Hematology Oncology PC	Flint	Michigan
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Aurora Health Center-Fond du Lac	Fond Du Lac	Wisconsin
United States	McFarland Clinic PC-Trinity Cancer Center	Fort Dodge	Iowa
United States	Trinity Regional Medical Center	Fort Dodge	Iowa
United States	Holy Cross Hospital	Fort Lauderdale	Florida
United States	Mercy Hospital Fort Smith	Fort Smith	Arkansas
United States	UT Southwestern/Simmons Cancer Center-Fort Worth	Fort Worth	Texas
United States	Essentia Health - Fosston	Fosston	Minnesota
United States	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio
United States	Dayton Physicians LLC-Atrium	Franklin	Ohio
United States	Unity Hospital	Fridley	Minnesota
United States	Saint Luke's Cancer Institute - Fruitland	Fruitland	Idaho
United States	Central Ohio Breast and Endocrine Surgery	Gahanna	Ohio
United States	Central Care Cancer Center - Garden City	Garden City	Kansas
United States	Northwestern Medicine Cancer Center Delnor	Geneva	Illinois
United States	Aurora Health Care Germantown Health Center	Germantown	Wisconsin
United States	MultiCare Gig Harbor Medical Park	Gig Harbor	Washington
United States	Smilow Cancer Hospital Care Center at Glastonbury	Glastonbury	Connecticut
United States	Glens Falls Hospital	Glens Falls	New York
United States	NorthShore University HealthSystem-Glenbrook Hospital	Glenview	Illinois
United States	National Jewish Health-Western Hematology Oncology	Golden	Colorado
United States	CTCA at Western Regional Medical Center	Goodyear	Arizona
United States	Aurora Cancer Care-Grafton	Grafton	Wisconsin
United States	CHI Health Saint Francis	Grand Island	Nebraska
United States	Saint Mary's Hospital and Regional Medical Center	Grand Junction	Colorado
United States	Helen DeVos Children's Hospital at Spectrum Health	Grand Rapids	Michigan
United States	Mercy Health Saint Mary's	Grand Rapids	Michigan
United States	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan
United States	Central Care Cancer Center - Great Bend	Great Bend	Kansas
United States	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana
United States	Great Falls Clinic	Great Falls	Montana
United States	North Colorado Medical Center	Greeley	Colorado
United States	Aurora BayCare Medical Center	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	Dayton Physicians LLC-Wayne	Greenville	Ohio
United States	Prisma Health Cancer Institute - Butternut	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Eastside	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Faris	Greenville	South Carolina
United States	Prisma Health Greenville Memorial Hospital	Greenville	South Carolina
United States	Wayne Hospital	Greenville	Ohio
United States	Self Regional Healthcare	Greenwood	South Carolina
United States	Prisma Health Cancer Institute - Greer	Greer	South Carolina
United States	Academic Hematology Oncology Specialists	Grosse Pointe Woods	Michigan
United States	Great Lakes Cancer Management Specialists-Van Elslander Cancer Center	Grosse Pointe Woods	Michigan
United States	Michigan Breast Specialists-Grosse Pointe Woods	Grosse Pointe Woods	Michigan
United States	Mount Carmel Grove City Hospital	Grove City	Ohio
United States	Smilow Cancer Hospital Care Center - Guiford	Guilford	Connecticut
United States	Smilow Cancer Hospital Care Center at Saint Francis	Hartford	Connecticut
United States	Ingalls Memorial Hospital	Harvey	Illinois
United States	Geisinger Medical Center-Cancer Center Hazleton	Hazleton	Pennsylvania
United States	Lehigh Valley Hospital-Hazleton	Hazleton	Pennsylvania
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-Horizon Ridge	Henderson	Nevada
United States	Comprehensive Cancer Centers of Nevada-Southeast Henderson	Henderson	Nevada
United States	Las Vegas Cancer Center-Henderson	Henderson	Nevada
United States	Las Vegas Urology - Green Valley	Henderson	Nevada
United States	Las Vegas Urology - Pebble	Henderson	Nevada
United States	OptumCare Cancer Care at Seven Hills	Henderson	Nevada
United States	Urology Specialists of Nevada - Green Valley	Henderson	Nevada
United States	Essentia Health Hibbing Clinic	Hibbing	Minnesota
United States	NorthShore University HealthSystem-Highland Park Hospital	Highland Park	Illinois
United States	Loyola Medicine Homer Glen	Homer Glen	Illinois
United States	CHI Saint Vincent Cancer Center Hot Springs	Hot Springs	Arkansas
United States	M D Anderson Cancer Center	Houston	Texas
United States	Indiana University/Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	Springmill Medical Center	Indianapolis	Indiana
United States	Swedish Cancer Institute-Issaquah	Issaquah	Washington
United States	Allegiance Health	Jackson	Michigan
United States	Essentia Health - Jamestown Clinic	Jamestown	North Dakota
United States	McFarland Clinic PC-Jefferson	Jefferson	Iowa
United States	Duly Health and Care Joliet	Joliet	Illinois
United States	Freeman Health System	Joplin	Missouri
United States	Mercy Hospital Joplin	Joplin	Missouri
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	Saint Luke's Hospital of Kansas City	Kansas City	Missouri
United States	CHI Health Good Samaritan	Kearney	Nebraska
United States	Vidant Oncology-Kenansville	Kenansville	North Carolina
United States	Kadlec Clinic Hematology and Oncology	Kennewick	Washington
United States	Aurora Cancer Care-Kenosha South	Kenosha	Wisconsin
United States	First Dayton Cancer Care	Kettering	Ohio
United States	Greater Dayton Cancer Center	Kettering	Ohio
United States	Kettering Medical Center	Kettering	Ohio
United States	Kingman Regional Medical Center	Kingman	Arizona
United States	Vidant Oncology-Kinston	Kinston	North Carolina
United States	Gundersen Lutheran Medical Center	La Crosse	Wisconsin
United States	UC San Diego Moores Cancer Center	La Jolla	California
United States	Providence Regional Cancer System-Lacey	Lacey	Washington
United States	Good Samaritan Medical Center	Lafayette	Colorado
United States	Saint Anthony Hospital	Lakewood	Colorado
United States	Saint Clare Hospital	Lakewood	Washington
United States	Fairfield Medical Center	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	Alliance for Childhood Diseases/Cure 4 the Kids Foundation	Las Vegas	Nevada
United States	Ann M Wierman MD LTD	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	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 - Town Center	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada-Summerlin	Las Vegas	Nevada
United States	Desert West Surgery	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	Hope Cancer Care of Nevada	Las Vegas	Nevada
United States	Las Vegas Cancer Center-Medical Center	Las Vegas	Nevada
United States	Las Vegas Prostate Cancer Center	Las Vegas	Nevada
United States	Las Vegas Urology - Cathedral Rock	Las Vegas	Nevada
United States	Las Vegas Urology - Pecos	Las Vegas	Nevada
United States	Las Vegas Urology - Smoke Ranch	Las Vegas	Nevada
United States	Las Vegas Urology - Sunset	Las Vegas	Nevada
United States	OptumCare Cancer Care at Charleston	Las Vegas	Nevada
United States	OptumCare Cancer Care at Fort Apache	Las Vegas	Nevada
United States	OptumCare Cancer Care at MountainView	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	Summerlin Hospital Medical Center	Las Vegas	Nevada
United States	Sunrise Hospital and Medical Center	Las Vegas	Nevada
United States	University Cancer Center	Las Vegas	Nevada
United States	University Medical Center of Southern Nevada	Las Vegas	Nevada
United States	Urology Specialists of Nevada - Central	Las Vegas	Nevada
United States	Urology Specialists of Nevada - Northwest	Las Vegas	Nevada
United States	Urology Specialists of Nevada - Southwest	Las Vegas	Nevada
United States	Saint Luke's East - Lee's Summit	Lee's Summit	Missouri
United States	Geisinger Medical Oncology-Lewisburg	Lewisburg	Pennsylvania
United States	Lewistown Hospital	Lewistown	Pennsylvania
United States	Saint Joseph Hospital East	Lexington	Kentucky
United States	Saint Joseph Radiation Oncology Resource Center	Lexington	Kentucky
United States	Saint Rita's Medical Center	Lima	Ohio
United States	Saint Elizabeth Regional Medical Center	Lincoln	Nebraska
United States	Littleton Adventist Hospital	Littleton	Colorado
United States	Rocky Mountain Cancer Centers-Littleton	Littleton	Colorado
United States	Hope Cancer Clinic	Livonia	Michigan
United States	Saint Mary Mercy Hospital	Livonia	Michigan
United States	Logan Regional Hospital	Logan	Utah
United States	Saint Joseph London	London	Kentucky
United States	Rocky Mountain Cancer Centers-Sky Ridge	Lone Tree	Colorado
United States	Sky Ridge Medical Center	Lone Tree	Colorado
United States	Longmont United Hospital	Longmont	Colorado
United States	Rocky Mountain Cancer Centers-Longmont	Longmont	Colorado
United States	PeaceHealth Saint John Medical Center	Longview	Washington
United States	Jewish Hospital	Louisville	Kentucky
United States	Jewish Hospital Medical Center Northeast	Louisville	Kentucky
United States	Saints Mary and Elizabeth Hospital	Louisville	Kentucky
United States	The James Graham Brown Cancer Center at University of Louisville	Louisville	Kentucky
United States	McKee Medical Center	Loveland	Colorado
United States	Great Lakes Cancer Management Specialists-Macomb Medical Campus	Macomb	Michigan
United States	Michigan Breast Specialists-Macomb Township	Macomb	Michigan
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin
United States	OhioHealth Mansfield Hospital	Mansfield	Ohio
United States	Fairview Clinics and Surgery Center Maple Grove	Maple Grove	Minnesota
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	Aurora Bay Area Medical Group-Marinette	Marinette	Wisconsin
United States	OhioHealth Marion General Hospital	Marion	Ohio
United States	Saint Mary's Oncology/Hematology Associates of Marlette	Marlette	Michigan
United States	McFarland Clinic PC-Marshalltown	Marshalltown	Iowa
United States	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin
United States	Contra Costa Regional Medical Center	Martinez	California
United States	WVUH-Berkely Medical Center	Martinsburg	West Virginia
United States	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois
United States	UH Seidman Cancer Center at Landerbrook Health Center	Mayfield Heights	Ohio
United States	Loyola University Medical Center	Maywood	Illinois
United States	Marjorie Weinberg Cancer Center at Loyola-Gottlieb	Melrose Park	Illinois
United States	UH Seidman Cancer Center at Lake Health Mentor Campus	Mentor	Ohio
United States	Idaho Urologic Institute-Meridian	Meridian	Idaho
United States	Saint Luke's Cancer Institute - Meridian	Meridian	Idaho
United States	UH Seidman Cancer Center at Southwest General Hospital	Middleburg Heights	Ohio
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	Ochsner LSU Health Monroe Medical Center	Monroe	Louisiana
United States	Toledo Clinic Cancer Centers-Monroe	Monroe	Michigan
United States	Monticello Cancer Center	Monticello	Minnesota
United States	West Virginia University Healthcare	Morgantown	West Virginia
United States	Morristown Medical Center	Morristown	New Jersey
United States	Good Samaritan Regional Health Center	Mount Vernon	Illinois
United States	Knox Community Hospital	Mount Vernon	Ohio
United States	ProHealth D N Greenwald Center	Mukwonago	Wisconsin
United States	Intermountain Medical Center	Murray	Utah
United States	Mercy Health Mercy Campus	Muskegon	Michigan
United States	Saint Alphonsus Medical Center-Nampa	Nampa	Idaho
United States	Saint Luke's Cancer Institute - Nampa	Nampa	Idaho
United States	Smilow Cancer Center/Yale-New Haven Hospital	New Haven	Connecticut
United States	Yale University	New Haven	Connecticut
United States	Ochsner Medical Center Jefferson	New Orleans	Louisiana
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	Licking Memorial Hospital	Newark	Ohio
United States	Newark Radiation Oncology	Newark	Ohio
United States	Providence Newberg Medical Center	Newberg	Oregon
United States	Illinois Cancer Specialists-Niles	Niles	Illinois
United States	Lakeland Hospital Niles	Niles	Michigan
United States	Yale-New Haven Hospital North Haven Medical Center	North Haven	Connecticut
United States	Cancer and Hematology Centers of Western Michigan - Norton Shores	Norton Shores	Michigan
United States	Henry Ford Medical Center-Columbus	Novi	Michigan
United States	Alta Bates Summit Medical Center - Summit Campus	Oakland	California
United States	Bay Area Tumor Institute	Oakland	California
United States	ProHealth Oconomowoc Memorial Hospital	Oconomowoc	Wisconsin
United States	Saint Vincent Hospital Cancer Center at Oconto Falls	Oconto Falls	Wisconsin
United States	McKay-Dee Hospital Center	Ogden	Utah
United States	Mercy Hospital Oklahoma City	Oklahoma City	Oklahoma
United States	Alegent Health Bergan Mercy Medical Center	Omaha	Nebraska
United States	Alegent Health Immanuel Medical Center	Omaha	Nebraska
United States	Alegent Health Lakeside Hospital	Omaha	Nebraska
United States	Creighton University Medical Center	Omaha	Nebraska
United States	Nebraska Medicine-Village Pointe	Omaha	Nebraska
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Saint Alphonsus Medical Center-Ontario	Ontario	Oregon
United States	Smilow Cancer Hospital-Orange Care Center	Orange	Connecticut
United States	Vince Lombardi Cancer Clinic - Oshkosh	Oshkosh	Wisconsin
United States	Saint Luke's South Hospital	Overland Park	Kansas
United States	Hope Cancer Care of Nevada-Pahrump	Pahrump	Nevada
United States	Midlands Community Hospital	Papillion	Nebraska
United States	Essentia Health - Park Rapids	Park Rapids	Minnesota
United States	Parker Adventist Hospital	Parker	Colorado
United States	Camden Clark Medical Center	Parkersburg	West Virginia
United States	Mercy Health Perrysburg Cancer Center	Perrysburg	Ohio
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	Cancer Center at Saint Joseph's	Phoenix	Arizona
United States	Mayo Clinic Hospital in Arizona	Phoenix	Arizona
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	West Penn Hospital	Pittsburgh	Pennsylvania
United States	21st Century Oncology-Pontiac	Pontiac	Michigan
United States	Hope Cancer Center	Pontiac	Michigan
United States	Newland Medical Associates-Pontiac	Pontiac	Michigan
United States	Saint Joseph Mercy Oakland	Pontiac	Michigan
United States	Huron Medical Center PC	Port Huron	Michigan
United States	Lake Huron Medical Center	Port Huron	Michigan
United States	Jefferson Healthcare	Port Townsend	Washington
United States	Oregon Health and Science University	Portland	Oregon
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	Southern Ohio Medical Center	Portsmouth	Ohio
United States	Kootenai Clinic Cancer Services - Post Falls	Post Falls	Idaho
United States	Pottstown Hospital	Pottstown	Pennsylvania
United States	Geisinger Cancer Services-Pottsville	Pottsville	Pennsylvania
United States	Harrison HealthPartners Hematology and Oncology-Poulsbo	Poulsbo	Washington
United States	Fairview Northland Medical Center	Princeton	Minnesota
United States	Utah Valley Regional Medical Center	Provo	Utah
United States	Saint Mary Corwin Medical Center	Pueblo	Colorado
United States	MultiCare Good Samaritan Hospital	Puyallup	Washington
United States	Aurora Cancer Care-Racine	Racine	Wisconsin
United States	Eisenhower Medical Center	Rancho Mirage	California
United States	Saint Charles Health System-Redmond	Redmond	Oregon
United States	Spectrum Health Reed City Hospital	Reed City	Michigan
United States	Radiation Oncology Associates	Reno	Nevada
United States	Renown Regional Medical Center	Reno	Nevada
United States	Saint Mary's Regional Medical Center	Reno	Nevada
United States	Valley Medical Center	Renton	Washington
United States	Marshfield Medical Center-Rice Lake	Rice Lake	Wisconsin
United States	UT Southwestern Clinical Center at Richardson/Plano	Richardson	Texas
United States	Vidant Oncology-Richlands	Richlands	North Carolina
United States	Reid Health	Richmond	Indiana
United States	Riverton Hospital	Riverton	Utah
United States	North Memorial Medical Health Center	Robbinsdale	Minnesota
United States	Mayo Clinic in Rochester	Rochester	Minnesota
United States	Great Lakes Cancer Management Specialists-Rochester Hills	Rochester Hills	Michigan
United States	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri
United States	Mercy Clinic-Rolla-Cancer and Hematology	Rolla	Missouri
United States	Ascension Saint Mary's Hospital	Saginaw	Michigan
United States	Oncology Hematology Associates of Saginaw Valley PC	Saginaw	Michigan
United States	Dixie Medical Center Regional Cancer Center	Saint George	Utah
United States	Heartland Regional Medical Center	Saint Joseph	Missouri
United States	Lakeland Medical Center Saint Joseph	Saint Joseph	Michigan
United States	Marie Yeager Cancer Center	Saint Joseph	Michigan
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Mercy Hospital South	Saint Louis	Missouri
United States	Saint Louis Cancer and Breast Institute-South City	Saint Louis	Missouri
United States	Siteman Cancer Center at Christian Hospital	Saint Louis	Missouri
United States	Siteman Cancer Center-South County	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
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	Siteman Cancer Center at Saint Peters Hospital	Saint Peters	Missouri
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	LDS Hospital	Salt Lake City	Utah
United States	Utah Cancer Specialists-Salt Lake City	Salt Lake City	Utah
United States	Pacific Central Coast Health Center-San Luis Obispo	San Luis Obispo	California
United States	Kootenai Cancer Clinic	Sandpoint	Idaho
United States	Essentia Health Sandstone	Sandstone	Minnesota
United States	UH Seidman Cancer Center at Firelands Regional Medical Center	Sandusky	Ohio
United States	Mission Hope Medical Oncology - Santa Maria	Santa Maria	California
United States	Lewis Cancer and Research Pavilion at Saint Joseph's/Candler	Savannah	Georgia
United States	Mayo Clinic in Arizona	Scottsdale	Arizona
United States	Community Medical Center	Scranton	Pennsylvania
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Pacific Gynecology Specialists	Seattle	Washington
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	Seattle Cancer Care Alliance at Northwest Hospital	Seattle	Washington
United States	Swedish Medical Center-Ballard Campus	Seattle	Washington
United States	Swedish Medical Center-Cherry Hill	Seattle	Washington
United States	Swedish Medical Center-First Hill	Seattle	Washington
United States	University of Washington Medical Center - Montlake	Seattle	Washington
United States	PeaceHealth United General Medical Center	Sedro-Woolley	Washington
United States	Geisinger Medical Oncology-Selinsgrove	Selinsgrove	Pennsylvania
United States	Prisma Health Cancer Institute - Seneca	Seneca	South Carolina
United States	Saint Francis Regional Medical Center	Shakopee	Minnesota
United States	Vince Lombardi Cancer Clinic-Sheboygan	Sheboygan	Wisconsin
United States	Henry Ford Macomb Health Center - Shelby Township	Shelby	Michigan
United States	Providence Regional Cancer System-Shelton	Shelton	Washington
United States	Jewish Hospital Medical Center South	Shepherdsville	Kentucky
United States	Welch Cancer Center	Sheridan	Wyoming
United States	LSU Health Sciences Center at Shreveport	Shreveport	Louisiana
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	North Shore Medical Center	Skokie	Illinois
United States	MultiCare Deaconess Cancer and Blood Specialty Center - Downtown	Spokane	Washington
United States	MultiCare Deaconess Cancer and Blood Specialty Center - North	Spokane	Washington
United States	MultiCare Deaconess Cancer and Blood Specialty Center - Valley	Spokane Valley	Washington
United States	CoxHealth South Hospital	Springfield	Missouri
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Mercy Medical Center	Springfield	Massachusetts
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	Bhadresh Nayak MD PC-Sterling Heights	Sterling Heights	Michigan
United States	Marshfield Clinic Stevens Point Center	Stevens Point	Wisconsin
United States	Lakeview Hospital	Stillwater	Minnesota
United States	Saint Vincent Hospital Cancer Center at Sturgeon Bay	Sturgeon Bay	Wisconsin
United States	Aurora Medical Center in Summit	Summit	Wisconsin
United States	Franciscan Research Center-Northwest Medical Plaza	Tacoma	Washington
United States	Mary Bridge Children's Hospital and Health Center	Tacoma	Washington
United States	MultiCare Tacoma General Hospital	Tacoma	Washington
United States	Ascension Saint Joseph Hospital	Tawas City	Michigan
United States	National Jewish Health-Northern Hematology Oncology	Thornton	Colorado
United States	Rocky Mountain Cancer Centers-Thornton	Thornton	Colorado
United States	Mercy Health - Saint Anne Hospital	Toledo	Ohio
United States	Saint Vincent Mercy Medical Center	Toledo	Ohio
United States	Toledo Clinic Cancer Centers-Toledo	Toledo	Ohio
United States	Cotton O'Neil Cancer Center / Stormont Vail Health	Topeka	Kansas
United States	Smilow Cancer Hospital-Torrington Care Center	Torrington	Connecticut
United States	Munson Medical Center	Traverse City	Michigan
United States	Dayton Physicians LLC-Upper Valley	Troy	Ohio
United States	Upper Valley Medical Center	Troy	Ohio
United States	Smilow Cancer Hospital Care Center-Trumbull	Trumbull	Connecticut
United States	Saint Luke's Cancer Institute - Twin Falls	Twin Falls	Idaho
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	PeaceHealth Southwest Medical Center	Vancouver	Washington
United States	Essentia Health Virginia Clinic	Virginia	Minnesota
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Providence Saint Mary Regional Cancer Center	Walla Walla	Washington
United States	Epic Care Cyberknife Center	Walnut Creek	California
United States	Advanced Breast Care Center PLLC	Warren	Michigan
United States	Great Lakes Cancer Management Specialists-Macomb Professional Building	Warren	Michigan
United States	Macomb Hematology Oncology PC	Warren	Michigan
United States	Michigan Breast Specialists-Warren	Warren	Michigan
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
United States	Saint Joseph Warren Hospital	Warren	Ohio
United States	Northwestern Medicine Cancer Center Warrenville	Warrenville	Illinois
United States	Mercy Hospital Washington	Washington	Missouri
United States	Smilow Cancer Hospital-Waterbury Care Center	Waterbury	Connecticut
United States	Smilow Cancer Hospital Care Center - Waterford	Waterford	Connecticut
United States	ProHealth Waukesha Memorial Hospital	Waukesha	Wisconsin
United States	UW Cancer Center at ProHealth Care	Waukesha	Wisconsin
United States	Aurora Cancer Care-Milwaukee West	Wauwatosa	Wisconsin
United States	Aurora West Allis Medical Center	West Allis	Wisconsin
United States	Henry Ford West Bloomfield Hospital	West Bloomfield	Michigan
United States	Saint Mary's Oncology/Hematology Associates of West Branch	West Branch	Michigan
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	Smilow Cancer Hospital Care Center - Westerly	Westerly	Rhode Island
United States	Saint Ann's Hospital	Westerville	Ohio
United States	UH Seidman Cancer Center at Saint John Medical Center	Westlake	Ohio
United States	Cleveland Clinic-Weston	Weston	Florida
United States	Marshfield Medical Center - Weston	Weston	Wisconsin
United States	SCL Health Lutheran Medical Center	Wheat Ridge	Colorado
United States	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania
United States	Rice Memorial Hospital	Willmar	Minnesota
United States	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota
United States	Fairview Lakes Medical Center	Wyoming	Minnesota
United States	Metro Health Hospital	Wyoming	Michigan
United States	North Star Lodge Cancer Center at Yakima Valley Memorial Hospital	Yakima	Washington
United States	Providence Regional Cancer System-Yelm	Yelm	Washington
United States	Rush-Copley Healthcare Center	Yorkville	Illinois
United States	Saint Elizabeth Youngstown Hospital	Youngstown	Ohio
United States	Huron Gastroenterology PC	Ypsilanti	Michigan
United States	IHA Hematology Oncology Consultants-Ann Arbor	Ypsilanti	Michigan
United States	Genesis Healthcare System Cancer Care Center	Zanesville	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
ECOG-ACRIN Cancer Research Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Cumulative dose calculated as the sum of all doses taken across all cycles	Cumulative dose will be calculated overall and by cycle. Data will be summarized by treatment arm with descriptive statistics and graphically over time. Patients will be classified into dichotomous groups based on a 75% relative dose intensity cutoff (< 75% versus [vs] >= 75% represents poor vs good treatment adherence). The proportion of patients with poor lenalidomide treatment adherence will be compared between arms using the Fisher's exact test. In addition, multi-variable logistic regression analysis will be conducted to identify the baseline factors associated with calculated good treatment adherence.	Up to 24 months
Other	Dose intensity calculated as cumulative dose received divided by treatment duration	Dose intensity will be calculated overall and by cycle. Data will be summarized by treatment arm with descriptive statistics and graphically over time. Patients will be classified into dichotomous groups based on a 75% relative dose intensity cutoff (< 75% vs >= 75% represents poor vs good treatment adherence). The proportion of patients with poor lenalidomide treatment adherence will be compared between arms using the Fisher's exact test. In addition, multi-variable logistic regression analysis will be conducted to identify the baseline factors associated with calculated good treatment adherence.	Up to 24 months
Other	Relative dose intensity calculated as the dose intensity divided by planned dose intensity	Dose intensity will be calculated overall and by cycle. Data will be summarized by treatment arm with descriptive statistics and graphically over time. Patients will be classified into dichotomous groups based on a 75% relative dose intensity cutoff (< 75% vs >= 75% represents poor vs good treatment adherence). The proportion of patients with poor lenalidomide treatment adherence will be compared between arms using the Fisher's exact test. In addition, multi-variable logistic regression analysis will be conducted to identify the baseline factors associated with calculated good treatment adherence.	Up to 24 months
Other	Duration of treatment	Treatment duration in each arm will be estimated using Kaplan-Meier methods and compared between arms with the log-rank test.	From randomization to date off treatment, or censored at the date of last treatment, assessed up to 24 months
Other	Time to progression	Will be estimated using the Kaplan-Meier method.	From randomization to progression, or censored at date of last disease evaluation, assessed up to 15 years
Other	Presence, frequency, interference, amount and/or severity of select patient reported outcomes (PRO)-CTCAEs	Descriptive statistics (mean, standard deviation, median, range) will be used to summarize selected PRO-CTCAEs tabulated at each cycle overall and by arm. Will map PRO-CTCAEs with provider reported adverse events (AEs) and evaluate differences in incidence and worst severity. Items correspond to 5 attributes measured [frequency (F), severity (S), interference (I), presence/absence (P) and amount (A)] based on multiple choice questions. Response for each attribute except P which is binary is on a 5-point Likert scale with 5 indicating 'almost constantly' frequency, 'very severe' severity, 'very much' amount or 'very much' interference. An overall PRO-CTCAE score will be calculated at each time point.	Assessed at each treatment cycle, from cycle 1 of treatment to end of treatment, up to 24 cycles of treatment (each cycle is 28 days)
Other	Overall PRO-CTCAE score	Defined as the sum of item scores on all symptomatic adverse events (AEs). Descriptive statistics will be used to summarize selected PRO-CTCAEs tabulated at each cycle overall and by arm. Will map PRO-CTCAEs with provider reported AEs and evaluate differences in incidence and worst severity. An overall PRO-CTCAE score will be calculated at each time point.	Up to 15 years
Other	Adherence Starts with Knowledge (ASK)-12 scores	Descriptive statistics will be used to summarize ASK-12 scores tabulated at cycles 7, 13 and 19 overall and by arm. Differences between arms will be evaluated based a t-test (or Wilcoxon rank sum test). Patients will also be classified into high versus low likelihood of medication adherence groups according to tertile distributions (lowest tertile vs second and top). Association between likelihood of medication adherence and calculated treatment adherence dichotomous groups will be evaluated in patients with both ASK-12 and treatment data at cycles 7, 13 and 19 post randomization. In addition, multivariable logistic regression analysis will be conducted to identify the baseline factors associated with low likelihood of medication adherence.	At 7, 13, and 19 cycles of treatment (each cycle is 28 days)
Other	PRO compliance rate	Defined as the proportion of patients who submit the given PRO instrument among those eligible at each time point which excludes those missing by design (due to death or disease progression, early treatment discontinuation).	Up to 15 years
Other	PRO completion rate	Defined as the proportion of patients who complete given PRO instrument based on the instrument's scoring system among those eligible at each time point.	Up to 15 years
Primary	Overall survival (OS)	Will be estimated using the Kaplan-Meier (KM) method and compared using a stratified log-rank test. Stratified cox proportional hazards regression will produce a treatment hazard ratio estimate.	From randomization to death due to any cause, or censored at date last known alive, assessed up to 15 years
Primary	Functional Assessment of Cancer Therapy-General (FACT-G) score	A general effect size measure of half standard deviation will be used to establish the minimally important difference. Descriptive statistics (mean, standard deviation [SD], median, range) will be used to evaluate the distribution of levels and changes for the set of health-related quality of life (QOL) evaluations. Levels and changes will also be assessed graphically. Changes from baseline will be analyzed using linear mixed models based on restricted maximum likelihood estimation with covariance matrix maximizing Akaike information criteria. Models with treatment, assessment time, and treatment by assessment time interaction with and without other predictors will be fit. If there is substantial missingness, will analyze the data according to the methods described in Schluchter and Schluchter, Greene and Beck.	Baseline to 24 cycles of treatment (each cycle is 28 days)
Secondary	Progression-free survival (PFS)	Will be estimated using the KM method and compared using a stratified log-rank test. Stratified cox proportional hazards regression will produce a treatment hazard ratio estimate.	From randomization until disease progression or death due to any cause, or censored at date of last disease evaluation, assessed up to 15 years
Secondary	Best response on treatment based on International Myeloma Working Group (IMWG) criteria	Response will be tabulated by category. Response rates of very good partial response (VGPR) or better and partial response (PR) or better will be compared using the Fisher's exact test. Ineligible patients are excluded from the analysis and unevaluable patients are counted in the denominator.	At 12 and 24 months
Secondary	Incidence of adverse events by worst grade and type for treated patients determined using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0	Will monitor the toxicities experienced by all treated patients. Will compare rates of worst grade 3 or higher non-hematologic treatment-related events using the Fisher's exact test.	Up to 28 days post-treatment
Secondary	Incidence of grade 3 or higher infusion-related reactions over course 1 determined based on CTCAE	Will monitor the toxicities experienced by all treated patients. Will compare rates of worst grade 3 or higher non-hematologic treatment-related events using the Fisher's exact test.	During cycle 1 of treatment (each cycle is 28 days)
Secondary	Stem cell (SC) mobilization failure	Defined as not collecting a minimum of 5x10^6 CD34 cells per kilogram weight. SC mobilization and type of growth factor support will be summarized overall and by treatment arm with descriptive statistics.	After 4 to 6 cycles of treatment (each cycle is 28 days)
Secondary	Early SC mobilization feasibility	Defined as the proportion of patients less than 65 years of age treated for 6 courses who opt for SC mobilization. SC mobilization and type of growth factor support will be summarized overall and by treatment arm with descriptive statistics.	Up to 6 cycles of treatment (each cycle is 28 days)
Secondary	Type of growth factor support	SC mobilization and type of growth factor support will be summarized overall and by treatment arm with descriptive statistics.	During 4 to 6 cycles of treatment (each cycle is 28 days)
Secondary	Change in FACT-G score	A general effect size measure of half standard deviation will be used to establish the minimally important difference. Descriptive statistics (mean, SD, median, range) will be used to evaluate the distribution of levels and changes for the set of health-related QOL evaluations. Levels and changes will also be assessed graphically. Changes from baseline will be analyzed using linear mixed models based on restricted maximum likelihood estimation with covariance matrix maximizing Akaike information criteria. Models with treatment, assessment time, and treatment by assessment time interaction with and without other predictors will be fit. If there is substantial missingness, will analyze the data according to the methods described in Schluchter and Schluchter, Greene and Beck.	From treatment end to 6 months post-treatment
Secondary	Levels of FACT-G score at each assessment time point	A general effect size measure of half standard deviation will be used to establish the minimally important difference. Descriptive statistics (mean, SD, median, range) will be used to evaluate the distribution of levels and changes for the set of health-related QOL evaluations. Levels and changes will also be assessed graphically. Changes from baseline will be analyzed using linear mixed models based on restricted maximum likelihood estimation with covariance matrix maximizing Akaike information criteria. Models with treatment, assessment time, and treatment by assessment time interaction with and without other predictors will be fit. If there is substantial missingness, will analyze the data according to the methods described in Schluchter and Schluchter, Greene and Beck.	From baseline, at 3, f7, 13, 19 cycles of treatment, and early discontinuation of treatment, assessed up to 24 cycles of treatment (each cycle is 28 days)
Secondary	Time to worsening of FACT-G	Will be analyzed with Kaplan-Meier methods and Cox regression with the related treatment arm as the only factor. Correlation between time to worsening of symptoms with PFS and OS will be assessed with Kendall's Tau adjusted for censored observations.	From baseline until a decrease of 9 points, or censored at date of last assessment, assessed up to 6 months post-treatment