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

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT00644228
• Collaborator: (none)
• Enrollment: 525
• Locations: 505
• Arms: 2
• Patients Per Site: 1

Study Details

Study Description

Brief Summary

This randomized phase III trial studies lenalidomide, dexamethasone, and bortezomib to see how well it works compared to dexamethasone and lenalidomide alone in treating patients with previously untreated multiple myeloma. Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. 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. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the cancer. It is not yet known whether lenalidomide and dexamethasone is more effective with or without bortezomib in treating multiple myeloma.

Condition or Disease	Intervention/Treatment	Phase
DS Stage I Plasma Cell Myeloma; DS Stage II Plasma Cell Myeloma; DS Stage III Plasma Cell Myeloma	Drug: Bortezomib; Drug: Dexamethasone; Other: Laboratory Biomarker Analysis; Drug: Lenalidomide	Phase 3

Detailed Description

PRIMARY OBJECTIVES:

1. To compare progression-free survival (PFS) in patients with newly diagnosed myeloma treated with lenalidomide plus low dose dexamethasone versus bortezomib plus lenalidomide and low dose dexamethasone.

SECONDARY OBJECTIVES:

1. Assess response using the new international response criteria. II. To bank specimens for future translational medicine research. III. Follow patients to assess overall survival and other long-term outcomes stratified by intent to transplant at progression.

TERTIARY OBJECTIVES:

1. To evaluate custom and genome-wide single nucleotide polymorphisms in correlation with biology, prognosis and outcome for both treatment regimens combined; to verify the findings recently obtained with the custom Bank on a Cure program (BOAC) single nucleotide polymorphism (SNP) chip on Total Therapy 2 (TT2) data with respect to bone disease in the cooperative group setting.

2. To use baseline gene expression profiling as a tool to evaluate the biology, prognostic and risk factors, and response to therapy for both treatment regimens combined. To validate John Shaughnessy's 70 gene risk model developed for Total Therapy 2 (TT2) in the cooperative group setting.

OUTLINE:

INDUCTION THERAPY: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive dexamethasone orally (PO) once daily (QD) on days 1, 8, 15, and 22 and lenalidomide PO QD on days 1-21. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive dexamethasone PO QD on days 1, 2, 4, 5, 8, 9, 11, and 12; lenalidomide PO QD on days 1-14; and bortezomib intravenously (IV) over 3-5 seconds on days 1, 4, 8, and 11. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity.

In both arms, patients who intend to undergo transplantation at relapse undergo peripheral blood stem cell collection, preferably after course 2.

MAINTENANCE THERAPY: After the completion of at least 4 courses (Arm I) or at least 6 courses (Arm II) of induction therapy, patients receive maintenance therapy comprising dexamethasone PO QD on days 1, 8, 15, and 22 and lenalidomide PO QD on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically for up to 6 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 525 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Phase III Trial of CC-5013 (Lenalidomide, NSC-703813) and Low Dose Dexamethasone (LLD) Versus Bortezomib (PS-341, NSC-681239), Lenalidomide and Low Dose Dexamethasone (BLLD) for Induction, in Patients With Previously Untreated Multiple Myeloma Without an Intent for Immediate Autologous Stem Cell Transplant
• Actual Study Start Date: Apr 1, 2008
• Actual Primary Completion Date: Jul 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm I (dexamethasone and lenalidomide) Patients receive dexamethasone PO QD on days 1, 8, 15, and 22 and lenalidomide PO QD on days 1-21. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.	Drug: Dexamethasone; Given PO; Other Names: Aacidexam Adexone Aknichthol Dexa Alba-Dex Alin Alin Depot Alin Oftalmico Amplidermis Anemul mono Auricularum Auxiloson Baycadron Baycuten Baycuten N Cortidexason Cortisumman Decacort Decadrol Decadron Decadron DP Decalix Decameth Decasone R.p. Dectancyl Dekacort Deltafluorene Deronil Desamethasone Desameton Dexa-Mamallet Dexa-Rhinosan Dexa-Scheroson Dexa-sine Dexacortal Dexacortin Dexafarma Dexafluorene Dexalocal Dexamecortin Dexameth Dexamethasone Intensol Dexamethasonum Dexamonozon Dexapos Dexinoral Dexone Dinormon Dxevo Fluorodelta Fortecortin Gammacorten Hemady Hexadecadrol Hexadrol Lokalison-F Loverine Methylfluorprednisolone Millicorten Mymethasone Orgadrone Spersadex TaperDex Visumetazone ZoDex ; Other: Laboratory Biomarker Analysis; Optional correlative studies; Drug: Lenalidomide; Given PO; Other Names: CC-5013 CC5013 CDC 501 Revlimid
Experimental: Arm II (dexamethasone, lenalidomide, bortezomib) Patients receive dexamethasone PO QD on days 1, 2, 4, 5, 8, 9, 11, and 12; lenalidomide PO QD on days 1-14; and bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity.	Drug: Bortezomib; Given IV; Other Names: [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid LDP 341 MLN341 PS-341 PS341 Velcade ; Drug: Dexamethasone; Given PO; Other Names: Aacidexam Adexone Aknichthol Dexa Alba-Dex Alin Alin Depot Alin Oftalmico Amplidermis Anemul mono Auricularum Auxiloson Baycadron Baycuten Baycuten N Cortidexason Cortisumman Decacort Decadrol Decadron Decadron DP Decalix Decameth Decasone R.p. Dectancyl Dekacort Deltafluorene Deronil Desamethasone Desameton Dexa-Mamallet Dexa-Rhinosan Dexa-Scheroson Dexa-sine Dexacortal Dexacortin Dexafarma Dexafluorene Dexalocal Dexamecortin Dexameth Dexamethasone Intensol Dexamethasonum Dexamonozon Dexapos Dexinoral Dexone Dinormon Dxevo Fluorodelta Fortecortin Gammacorten Hemady Hexadecadrol Hexadrol Lokalison-F Loverine Methylfluorprednisolone Millicorten Mymethasone Orgadrone Spersadex TaperDex Visumetazone ZoDex ; Other: Laboratory Biomarker Analysis; Optional correlative studies; Drug: Lenalidomide; Given PO; Other Names: CC-5013 CC5013 CDC 501 Revlimid

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival [From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause, assessed up to 6 years]

   Unstratified median progression-free survival in months.

Secondary Outcome Measures

1. Overall Survival [Up to 6 years]

   Unstratified median overall survival in months.

2. Response Rates () [Up to 6 years]

   The response rate was calculated as the number of patients with documented confirmed partial response (PR) or better, which includes confirmed/unconfirmed stringent complete response (sCR), confirmed/unconfirmed complete response (CR), confirmed/unconfirmed very good partial response (VGPR), or confirmed partial response (PR), as best response divided by the total number of evaluable patients, in each arm. Patients with measurable disease, as defined in the protocol, are evaluable. Response rates were compared between the two treatment arms using a stratified Cochran-Mantel-Haenszel test. Response designations were based on the International Uniform Response Criteria for Multiple Myeloma. Due to the complexity of these criteria, the details of these criteria have been omitted.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients must have newly diagnosed multiple myeloma with measurable disease; patients with non-secretory multiple myeloma (MM) based upon standard M-component criteria (i.e., measurable serum/urine M-component) are not eligible for this study; exception: patients with non-secretory MM will be eligible only if the baseline serum Freelite is elevated (Note that serum Freelite must be drawn; serum light chains are not acceptable); all tests for establishing baseline disease status must be completed within 28 days prior to registration and documented on the baseline and follow-up tumor assessment form for multiple myeloma

• Patients must have received no prior chemotherapy for this disease; patients must have received no prior radiotherapy to a large area of the pelvis (more than half of the pelvis); prior steroid treatment is allowed provided treatment was not more than 2 weeks in duration; patients must not have received any prior treatment with bortezomib or lenalidomide

• Patients must have a Zubrod performance status (PS) of 0 - 3; NOTE: patients with PS 3 are eligible only if it is documented by the treating physician that the patient's multiple myeloma is the central cause of his/her disability; patients who have a PS of 3 due to other concurrent medical conditions are not eligible for this trial

• Platelet count >= 80 x 10^3/mcL; must be obtained within 28 days prior to registration; exception: patients with biopsy-proven heavy-marrow involvement, as defined by having at least 30% marrow cellularity, with > 50% of the cells being malignant plasma cells (documented marrow results required); in this case, although there are no required lower limits of normal for the blood counts, the treating physician must use his/her medical judgment as to the appropriateness of this study therapy for these patients

• Absolute neutrophil count (ANC) >= 1 x 10^3/mcL; must be obtained within 28 days prior to registration; exception: patients with biopsy-proven heavy-marrow involvement, as defined by having at least 30% marrow cellularity, with > 50% of the cells being malignant plasma cells (documented marrow results required); in this case, although there are no required lower limits of normal for the blood counts, the treating physician must use his/her medical judgment as to the appropriateness of this study therapy for these patients

• Hemoglobin (including patients who have been either transfused or treated with erythropoietin [EPO]) >= 9 g/dL; must be obtained within 28 days prior to registration; exception: patients with biopsy-proven heavy-marrow involvement, as defined by having at least 30% marrow cellularity, with > 50% of the cells being malignant plasma cells (documented marrow results required); in this case, although there are no required lower limits of normal for the blood counts, the treating physician must use his/her medical judgment as to the appropriateness of this study therapy for these patients

• Patients must be offered participation in the Myeloma Specimen Repository for banking and future research; with the patient's consent, bone marrow aspirates and serum specimens will be submitted to the Myeloma Specimen Repository for additional testing and banking (including SNP testing); patient consent must be obtained before specimens may be submitted

• Patients must have baseline skeletal survey to include lateral skull, anterior-posterior (AP) pelvis and posterior-anterior (PA) chest within 28 days prior to registration

• Institutions must submit a local cytogenetics report and fluorescence in situ hybridization (FISH) analysis report obtained prior to enrollment to S0777; for FISH analysis two probes will be utilized: LSI 13 (RBI) 13q14 SpectrumOrange Probe for detection of chromosome 13 deletion and LSI p53 (17p13.1) SpectrumOrange probe for detection of tumor protein (p)53 locus on chromosome 17; if these exact probes are not available locally, it is acceptable to submit results using local protocol; this must be noted on the prestudy form; NOTE: it is not required that the results of the FISH analysis be known prior to registration, only that pre-registration specimens be drawn and sent for analysis prior to registration, and the FISH analysis report be submitted

• Patients with pathologic fractures, pneumonia at diagnosis or symptomatic hyperviscosity must have these conditions attended to prior to registration (i.e., intramedullary rod, I.V. antibiotics, plasmapheresis)

• Patients must have a calculated or measured creatinine clearance > 30 cc/min; measured creatinine clearance or serum creatinine used in calculation must be obtained within 28 days prior to registration

• Patients must not have uncontrolled, active infection requiring intravenous antibiotics, New York Heart Association (NYHA) class III or class IV heart failure, myocardial infarction within the last 6 months, history of treatment for clinically significant ventricular cardiac arrhythmias, poorly controlled hypertension, or poorly controlled diabetes mellitus; patients must have undergone an electrocardiogram (EKG) within 28 days prior to registration

• Patients must not have any psychiatric illness that could potentially interfere with the completion of treatment according to this protocol

• Patients must not be hepatitis B, hepatitis C or human immunodeficiency virus (HIV) positive; patients must have a negative hepatitis B and HIV test performed within 28 days prior to registration; exception: treatment-sensitive HIV infection patients will be eligible provided that immunological and virologic indices are indicative of favorable long-term survival prospects on the basis of HIV infection, but whose life expectancy is limited predominantly by multiple myeloma rather than HIV infection in the judgment of the treating physician

• Patients must not have a history of cerebral vascular accident with persistent neurologic deficits

• Patients must be able to take aspirin 325 mg daily (or enoxaparin 40 mg subcutaneously [SQ] daily if patient is unable to take aspirin) as prophylactic anticoagulation; exception: patients receiving anticoagulation therapy such as Coumadin or heparin will NOT receive aspirin, and therefore need not be able to take it

• Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 - 14 days and again within 24 hours prior to starting cycle 1 of lenalidomide; further, they must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control: one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before starting lenalidomide; FCBP must also agree to ongoing pregnancy testing; men must agree to use a latex condom during sexual contact with a FCBP, even if they have had a successful vasectomy; a FCBP is a sexually mature woman who: has not undergone a hysterectomy or bilateral oophorectomy; or has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months); all patients must be counseled by a trained counselor every 28 days about pregnancy precautions and risks of fetal exposure

• No prior malignancy is allowed except for adequately treated basal cell (or squamous cell) skin cancer, in situ cervical cancer or other cancer for which the patient has been disease-free for five years

• Patients must be offered participation in gene expression profiling (GEP) molecular studies for the evaluation of genetic polymorphisms

• All patients must be informed of the investigational nature of this study and must sign and give written consent in accordance with institutional federal guidelines

• At the time of patient registration, the treating institution's name and identification (ID) number must be provided to the statistical center in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered into the data base

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Providence Alaska Medical Center	Anchorage	Alaska	United States	99508
2	Mayo Clinic in Arizona	Scottsdale	Arizona	United States	85259
3	University of Arizona Cancer Center-Orange Grove Campus	Tucson	Arizona	United States	85704
4	Banner University Medical Center - Tucson	Tucson	Arizona	United States	85719
5	University of Arizona Cancer Center-North Campus	Tucson	Arizona	United States	85719
6	University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
7	Kaiser Permanente-Deer Valley Medical Center	Antioch	California	United States	94531
8	PCR Oncology	Arroyo Grande	California	United States	93420
9	Alta Bates Summit Medical Center-Herrick Campus	Berkeley	California	United States	94704
10	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California	United States	91505
11	Mills-Peninsula Medical Center	Burlingame	California	United States	94010
12	Kaiser Permanente-Fremont	Fremont	California	United States	94538
13	Kaiser Permanente-Fresno	Fresno	California	United States	93720
14	Saint Jude Medical Center	Fullerton	California	United States	92835
15	Marin General Hospital	Greenbrae	California	United States	94904
16	Fremont - Rideout Cancer Center	Marysville	California	United States	95901
17	Providence Holy Cross Medical Center	Mission Hills	California	United States	91346-9600
18	Palo Alto Medical Foundation-Camino Division	Mountain View	California	United States	94040
19	Sutter Cancer Research Consortium	Novato	California	United States	94945
20	Kaiser Permanente-Oakland	Oakland	California	United States	94611
21	Saint Joseph Hospital - Orange	Orange	California	United States	92868
22	Desert Regional Medical Center	Palm Springs	California	United States	92262
23	Palo Alto Medical Foundation Health Care	Palo Alto	California	United States	94301
24	Valley Medical Oncology Consultants	Pleasanton	California	United States	94588
25	Eisenhower Medical Center	Rancho Mirage	California	United States	92270
26	Kaiser Permanente-Redwood City	Redwood City	California	United States	94063
27	Kaiser Permanente-Richmond	Richmond	California	United States	94801
28	Kaiser Permanente-Roseville	Roseville	California	United States	95661
29	University of California Davis Comprehensive Cancer Center	Sacramento	California	United States	95817
30	Kaiser Permanente-South Sacramento	Sacramento	California	United States	95823
31	Kaiser Permanente - Sacramento	Sacramento	California	United States	95825
32	California Pacific Medical Center-Pacific Campus	San Francisco	California	United States	94115
33	Kaiser Permanente-San Francisco	San Francisco	California	United States	94115
34	Kaiser Permanente-Santa Teresa-San Jose	San Jose	California	United States	95119
35	Kaiser Permanente San Leandro	San Leandro	California	United States	94577
36	Kaiser Permanente-San Rafael	San Rafael	California	United States	94903
37	Kaiser Permanente Medical Center - Santa Clara	Santa Clara	California	United States	95051
38	Kaiser Permanente-Santa Rosa	Santa Rosa	California	United States	95403
39	Kaiser Permanente-South San Francisco	South San Francisco	California	United States	94080
40	Kaiser Permanente-Stockton	Stockton	California	United States	95210
41	Gene Upshaw Memorial Tahoe Forest Cancer Center	Truckee	California	United States	96161
42	Kaiser Permanente Medical Center-Vacaville	Vacaville	California	United States	95688
43	Kaiser Permanente-Vallejo	Vallejo	California	United States	94589
44	Sutter Solano Medical Center/Cancer Center	Vallejo	California	United States	94589
45	Kaiser Permanente-Walnut Creek	Walnut Creek	California	United States	94596
46	The Medical Center of Aurora	Aurora	Colorado	United States	80012
47	University of Colorado Hospital	Aurora	Colorado	United States	80045
48	Boulder Community Hospital	Boulder	Colorado	United States	80301
49	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado	United States	80907
50	Denver Health Medical Center	Denver	Colorado	United States	80204
51	Kaiser Permanente-Franklin	Denver	Colorado	United States	80205
52	Porter Adventist Hospital	Denver	Colorado	United States	80210
53	University of Colorado	Denver	Colorado	United States	80217-3364
54	Presbyterian - Saint Lukes Medical Center - Health One	Denver	Colorado	United States	80218
55	SCL Health Saint Joseph Hospital	Denver	Colorado	United States	80218
56	Rose Medical Center	Denver	Colorado	United States	80220
57	Western States Cancer Research NCORP	Denver	Colorado	United States	80222
58	Swedish Medical Center	Englewood	Colorado	United States	80113
59	Poudre Valley Hospital	Fort Collins	Colorado	United States	80524
60	Saint Mary's Hospital and Regional Medical Center	Grand Junction	Colorado	United States	81501
61	North Colorado Medical Center	Greeley	Colorado	United States	80631
62	Kaiser Permanente-Rock Creek	Lafayette	Colorado	United States	80026
63	Saint Anthony Hospital	Lakewood	Colorado	United States	80228
64	Sky Ridge Medical Center	Lone Tree	Colorado	United States	80124
65	Longmont United Hospital	Longmont	Colorado	United States	80501
66	McKee Medical Center	Loveland	Colorado	United States	80539
67	Parker Adventist Hospital	Parker	Colorado	United States	80138
68	Saint Mary Corwin Medical Center	Pueblo	Colorado	United States	81004
69	North Suburban Medical Center	Thornton	Colorado	United States	80229
70	SCL Health Lutheran Medical Center	Wheat Ridge	Colorado	United States	80033
71	Danbury Hospital	Danbury	Connecticut	United States	06810
72	Smilow Cancer Hospital Care Center at Saint Francis	Hartford	Connecticut	United States	06105
73	The Hospital of Central Connecticut	New Britain	Connecticut	United States	06050
74	Norwalk Hospital	Norwalk	Connecticut	United States	06856
75	Beebe Medical Center	Lewes	Delaware	United States	19958
76	Christiana Care Health System-Christiana Hospital	Newark	Delaware	United States	19718
77	Mayo Clinic in Florida	Jacksonville	Florida	United States	32224-9980
78	AdventHealth Orlando	Orlando	Florida	United States	32803
79	Orlando Health Cancer Institute	Orlando	Florida	United States	32806
80	Martin Medical Center	Stuart	Florida	United States	34994
81	Robert and Carol Weissman Cancer Center at Martin Health	Stuart	Florida	United States	34994
82	Martin Hospital South	Stuart	Florida	United States	34997
83	Piedmont Hospital	Atlanta	Georgia	United States	30309
84	Atlanta Regional CCOP	Atlanta	Georgia	United States	30342
85	Emory Saint Joseph's Hospital	Atlanta	Georgia	United States	30342
86	Northside Hospital	Atlanta	Georgia	United States	30342
87	WellStar Cobb Hospital	Austell	Georgia	United States	30106
88	John B Amos Cancer Center	Columbus	Georgia	United States	31904
89	Dekalb Medical Center	Decatur	Georgia	United States	30033
90	Piedmont Fayette Hospital	Fayetteville	Georgia	United States	30214
91	Northside Hospital - Gwinnett	Lawrenceville	Georgia	United States	30046
92	Wellstar Kennestone Hospital	Marietta	Georgia	United States	30060
93	Southern Regional Medical Center	Riverdale	Georgia	United States	30274
94	Harbin Clinic Medical Oncology and Clinical Research	Rome	Georgia	United States	30165
95	Pali Momi Medical Center	'Aiea	Hawaii	United States	96701
96	Hawaii Cancer Care Inc - Waterfront Plaza	Honolulu	Hawaii	United States	96813
97	Queen's Medical Center	Honolulu	Hawaii	United States	96813
98	Straub Clinic and Hospital	Honolulu	Hawaii	United States	96813
99	University of Hawaii Cancer Center	Honolulu	Hawaii	United States	96813
100	Queen's Cancer Center - Kuakini	Honolulu	Hawaii	United States	96817
101	The Cancer Center of Hawaii-Liliha	Honolulu	Hawaii	United States	96817
102	Kaiser Permanente Moanalua Medical Center	Honolulu	Hawaii	United States	96819
103	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii	United States	96826
104	Castle Medical Center	Kailua	Hawaii	United States	96734
105	Wilcox Memorial Hospital and Kauai Medical Clinic	Lihue	Hawaii	United States	96766
106	Maui Memorial Medical Center	Wailuku	Hawaii	United States	96793
107	Pacific Cancer Institute of Maui	Wailuku	Hawaii	United States	96793
108	Saint Anthony's Health	Alton	Illinois	United States	62002
109	Rush - Copley Medical Center	Aurora	Illinois	United States	60504
110	MacNeal Hospital and Cancer Center	Berwyn	Illinois	United States	60402
111	Saint Joseph Medical Center	Bloomington	Illinois	United States	61701
112	Illinois CancerCare-Bloomington	Bloomington	Illinois	United States	61704
113	Graham Hospital Association	Canton	Illinois	United States	61520
114	Illinois CancerCare-Canton	Canton	Illinois	United States	61520
115	Illinois CancerCare-Carthage	Carthage	Illinois	United States	62321
116	Memorial Hospital	Carthage	Illinois	United States	62321
117	Hematology and Oncology Associates	Chicago	Illinois	United States	60611
118	Northwestern University	Chicago	Illinois	United States	60611
119	University of Illinois	Chicago	Illinois	United States	60612
120	Decatur Memorial Hospital	Decatur	Illinois	United States	62526
121	Heartland Cancer Research NCORP	Decatur	Illinois	United States	62526
122	Advocate Good Samaritan Hospital	Downers Grove	Illinois	United States	60515
123	Eureka Hospital	Eureka	Illinois	United States	61530
124	Illinois CancerCare-Eureka	Eureka	Illinois	United States	61530
125	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois	United States	60201
126	Galesburg Cottage Hospital	Galesburg	Illinois	United States	61401
127	Illinois CancerCare-Galesburg	Galesburg	Illinois	United States	61401
128	Illinois CancerCare-Havana	Havana	Illinois	United States	62644
129	Mason District Hospital	Havana	Illinois	United States	62644
130	Hematology Oncology Associates of Illinois-Highland Park	Highland Park	Illinois	United States	60035
131	Hopedale Medical Complex - Hospital	Hopedale	Illinois	United States	61747
132	Midwest Center for Hematology Oncology	Joliet	Illinois	United States	60432
133	Duly Health and Care Joliet	Joliet	Illinois	United States	60435
134	Presence Saint Mary's Hospital	Kankakee	Illinois	United States	60901
135	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois	United States	61443
136	AMG Libertyville - Oncology	Libertyville	Illinois	United States	60048
137	Illinois CancerCare-Macomb	Macomb	Illinois	United States	61455
138	Mcdonough District Hospital	Macomb	Illinois	United States	61455
139	Loyola University Medical Center	Maywood	Illinois	United States	60153
140	Holy Family Medical Center	Monmouth	Illinois	United States	61462
141	Illinois CancerCare-Monmouth	Monmouth	Illinois	United States	61462
142	Good Samaritan Regional Health Center	Mount Vernon	Illinois	United States	62864
143	DuPage Medical Group-Ogden	Naperville	Illinois	United States	60563
144	Illinois Cancer Specialists-Niles	Niles	Illinois	United States	60714
145	Bromenn Regional Medical Center	Normal	Illinois	United States	61761
146	Carle Cancer Institute Normal	Normal	Illinois	United States	61761
147	Illinois CancerCare-Community Cancer Center	Normal	Illinois	United States	61761
148	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois	United States	61350
149	Ottawa Regional Hospital and Healthcare Center	Ottawa	Illinois	United States	61350
150	Illinois CancerCare-Pekin	Pekin	Illinois	United States	61554
151	OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center	Pekin	Illinois	United States	61554
152	Pekin Hospital	Pekin	Illinois	United States	61554
153	Proctor Hospital	Peoria	Illinois	United States	61614
154	Illinois CancerCare-Peoria	Peoria	Illinois	United States	61615
155	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61636
156	OSF Saint Francis Medical Center	Peoria	Illinois	United States	61637
157	Illinois CancerCare-Peru	Peru	Illinois	United States	61354
158	Illinois Valley Hospital	Peru	Illinois	United States	61354
159	Illinois CancerCare-Princeton	Princeton	Illinois	United States	61356
160	Perry Memorial Hospital	Princeton	Illinois	United States	61356
161	Hematology Oncology Associates of Illinois - Skokie	Skokie	Illinois	United States	60076
162	Illinois CancerCare-Spring Valley	Spring Valley	Illinois	United States	61362
163	Saint Margaret's Hospital	Spring Valley	Illinois	United States	61362
164	Memorial Medical Center	Springfield	Illinois	United States	62781
165	Carle Cancer Center	Urbana	Illinois	United States	61801
166	Northwestern Medicine Cancer Center Warrenville	Warrenville	Illinois	United States	60555
167	Northwestern Medicine Central DuPage Hospital	Winfield	Illinois	United States	60190
168	Franciscan Saint Francis Health-Beech Grove	Beech Grove	Indiana	United States	46107
169	Elkhart Clinic	Elkhart	Indiana	United States	46514-2098
170	Michiana Hematology Oncology PC-Elkhart	Elkhart	Indiana	United States	46514
171	Elkhart General Hospital	Elkhart	Indiana	United States	46515
172	Fort Wayne Medical Oncology and Hematology Inc-Parkview	Fort Wayne	Indiana	United States	46845
173	Goshen Center for Cancer Care	Goshen	Indiana	United States	46526
174	Community Howard Regional Health	Kokomo	Indiana	United States	46904
175	IU Health La Porte Hospital	La Porte	Indiana	United States	46350
176	Franciscan Saint Anthony Health-Michigan City	Michigan City	Indiana	United States	46360
177	Michiana Hematology Oncology PC-Mishawaka	Mishawaka	Indiana	United States	46545
178	Saint Joseph Regional Medical Center-Mishawaka	Mishawaka	Indiana	United States	46545
179	The Community Hospital	Munster	Indiana	United States	46321
180	Michiana Hematology Oncology PC-Plymouth	Plymouth	Indiana	United States	46563
181	Reid Health	Richmond	Indiana	United States	47374
182	Memorial Hospital of South Bend	South Bend	Indiana	United States	46601
183	Michiana Hematology Oncology PC-South Bend	South Bend	Indiana	United States	46601
184	Northern Indiana Cancer Research Consortium	South Bend	Indiana	United States	46628
185	Michiana Hematology Oncology PC-Westville	Westville	Indiana	United States	46391
186	Mercy Hospital	Cedar Rapids	Iowa	United States	52403
187	Oncology Associates at Mercy Medical Center	Cedar Rapids	Iowa	United States	52403
188	Iowa-Wide Oncology Research Coalition NCORP	Des Moines	Iowa	United States	50309
189	Mercy Medical Center - North Iowa	Mason City	Iowa	United States	50401
190	Ottumwa Regional Health Center	Ottumwa	Iowa	United States	52501
191	Siouxland Regional Cancer Center	Sioux City	Iowa	United States	51101
192	Mercy Medical Center-Sioux City	Sioux City	Iowa	United States	51102
193	Saint Luke's Regional Medical Center	Sioux City	Iowa	United States	51104
194	Lawrence Memorial Hospital	Lawrence	Kansas	United States	66044
195	Menorah Medical Center	Overland Park	Kansas	United States	66209
196	Saint Luke's South Hospital	Overland Park	Kansas	United States	66213
197	Kansas City NCI Community Oncology Research Program	Prairie Village	Kansas	United States	66208
198	Salina Regional Health Center	Salina	Kansas	United States	67401
199	Advent Health - Shawnee Mission Medical Center	Shawnee Mission	Kansas	United States	66204
200	Cotton O'Neil Cancer Center / Stormont Vail Health	Topeka	Kansas	United States	66606
201	Wesley Medical Center	Wichita	Kansas	United States	67214
202	Wichita NCI Community Oncology Research Program	Wichita	Kansas	United States	67214
203	Mary Bird Perkins Cancer Center	Baton Rouge	Louisiana	United States	70809
204	Louisiana State University Health Science Center	New Orleans	Louisiana	United States	70112
205	University Medical Center New Orleans	New Orleans	Louisiana	United States	70112
206	Harold Alfond Center for Cancer Care	Augusta	Maine	United States	04330
207	Eastern Maine Medical Center	Bangor	Maine	United States	04401
208	York Hospital	York	Maine	United States	03909
209	Greater Baltimore Medical Center	Baltimore	Maryland	United States	21204
210	Sinai Hospital of Baltimore	Baltimore	Maryland	United States	21215
211	Christiana Care - Union Hospital	Elkton	Maryland	United States	21921
212	Boston Medical Center	Boston	Massachusetts	United States	02118
213	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
214	Commonwealth Hematology Oncology PC-Concord	Concord	Massachusetts	United States	01742
215	Dana Farber Community Cancer Care-Haverhill	Haverhill	Massachusetts	United States	01830
216	Dana Farber-Merrimack Valley	Methuen	Massachusetts	United States	01844
217	Dana Farber Community Cancer Care-Quincy	Quincy	Massachusetts	United States	02169
218	Baystate Medical Center	Springfield	Massachusetts	United States	01199
219	Dana Farber Community Cancer Care-Stoneham	Stoneham	Massachusetts	United States	02180
220	Dana Farber Community Cancer Care-Weymouth	Weymouth	Massachusetts	United States	02189
221	Commonwealth Hematology Oncology PC-Worcester	Worcester	Massachusetts	United States	01605
222	Bixby Medical Center	Adrian	Michigan	United States	49221
223	Hickman Cancer Center	Adrian	Michigan	United States	49221
224	Michigan Cancer Research Consortium NCORP	Ann Arbor	Michigan	United States	48106
225	Saint Joseph Mercy Hospital	Ann Arbor	Michigan	United States	48106
226	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109
227	Bronson Battle Creek	Battle Creek	Michigan	United States	49017
228	Spectrum Health Big Rapids Hospital	Big Rapids	Michigan	United States	49307
229	Beaumont Hospital - Dearborn	Dearborn	Michigan	United States	48124
230	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan	United States	48201
231	Ascension Saint John Hospital	Detroit	Michigan	United States	48236
232	Green Bay Oncology - Escanaba	Escanaba	Michigan	United States	49829
233	Hurley Medical Center	Flint	Michigan	United States	48503
234	Genesys Regional Medical Center-West Flint Campus	Flint	Michigan	United States	48532
235	Cancer Research Consortium of West Michigan NCORP	Grand Rapids	Michigan	United States	49503
236	Mercy Health Saint Mary's	Grand Rapids	Michigan	United States	49503
237	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan	United States	49503
238	Holland Community Hospital	Holland	Michigan	United States	49423
239	Green Bay Oncology - Iron Mountain	Iron Mountain	Michigan	United States	49801
240	Allegiance Health	Jackson	Michigan	United States	49201
241	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
242	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007
243	Borgess Medical Center	Kalamazoo	Michigan	United States	49048
244	Sparrow Hospital	Lansing	Michigan	United States	48912
245	Trinity Health Saint Mary Mercy Livonia Hospital	Livonia	Michigan	United States	48154
246	UP Health System Marquette	Marquette	Michigan	United States	49855
247	Mercy Memorial Hospital	Monroe	Michigan	United States	48162
248	Toledo Clinic Cancer Centers-Monroe	Monroe	Michigan	United States	48162
249	McLaren Cancer Institute-Macomb	Mount Clemens	Michigan	United States	48043
250	Mercy Health Partners-Hackley Campus	Muskegon	Michigan	United States	49442
251	Mercy Health Mercy Campus	Muskegon	Michigan	United States	49444
252	Lakeland Hospital Niles	Niles	Michigan	United States	49120
253	Saint Joseph Mercy Oakland	Pontiac	Michigan	United States	48341
254	Lake Huron Medical Center	Port Huron	Michigan	United States	48060
255	William Beaumont Hospital-Royal Oak	Royal Oak	Michigan	United States	48073
256	Ascension Saint Mary's Hospital	Saginaw	Michigan	United States	48601
257	Lakeland Medical Center Saint Joseph	Saint Joseph	Michigan	United States	49085
258	Marie Yeager Cancer Center	Saint Joseph	Michigan	United States	49085
259	Ascension Providence Hospitals - Southfield	Southfield	Michigan	United States	48075
260	Munson Medical Center	Traverse City	Michigan	United States	49684
261	Saint John Macomb-Oakland Hospital	Warren	Michigan	United States	48093
262	Metro Health Hospital	Wyoming	Michigan	United States	49519
263	Medini, Eitan MD (UIA Investigator)	Alexandria	Minnesota	United States	56308
264	Essentia Health Saint Joseph's Medical Center	Brainerd	Minnesota	United States	56401
265	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
266	Mercy Hospital	Coon Rapids	Minnesota	United States	55433
267	Essentia Health Cancer Center	Duluth	Minnesota	United States	55805
268	Essentia Health Saint Mary's Medical Center	Duluth	Minnesota	United States	55805
269	Miller-Dwan Hospital	Duluth	Minnesota	United States	55805
270	Fairview Southdale Hospital	Edina	Minnesota	United States	55435
271	Etzell, Paul S MD (UIA Investigator)	Fergus Falls	Minnesota	United States	56537
272	Swenson, Wade II, MD (UIA Investigator)	Fergus Falls	Minnesota	United States	56537
273	Unity Hospital	Fridley	Minnesota	United States	55432
274	Hutchinson Area Health Care	Hutchinson	Minnesota	United States	55350
275	Meeker County Memorial Hospital	Litchfield	Minnesota	United States	55355
276	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota	United States	55109
277	Saint John's Hospital - Healtheast	Maplewood	Minnesota	United States	55109
278	Abbott-Northwestern Hospital	Minneapolis	Minnesota	United States	55407
279	Virginia Piper Cancer Institute	Minneapolis	Minnesota	United States	55407
280	Hennepin County Medical Center	Minneapolis	Minnesota	United States	55415
281	North Memorial Medical Health Center	Robbinsdale	Minnesota	United States	55422
282	Mayo Clinic in Rochester	Rochester	Minnesota	United States	55905
283	Coborn Cancer Center at Saint Cloud Hospital	Saint Cloud	Minnesota	United States	56303
284	Saint Cloud Hospital	Saint Cloud	Minnesota	United States	56303
285	Metro Minnesota Community Oncology Research Consortium	Saint Louis Park	Minnesota	United States	55416
286	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota	United States	55416
287	Regions Hospital	Saint Paul	Minnesota	United States	55101
288	Saint Joseph's Hospital - Healtheast	Saint Paul	Minnesota	United States	55102
289	United Hospital	Saint Paul	Minnesota	United States	55102
290	Saint Francis Regional Medical Center	Shakopee	Minnesota	United States	55379
291	Lakeview Hospital	Stillwater	Minnesota	United States	55082
292	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
293	Rice Memorial Hospital	Willmar	Minnesota	United States	56201
294	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota	United States	55125
295	Woodwinds Health Campus	Woodbury	Minnesota	United States	55125
296	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
297	Keesler Medical Center	Keesler Air Force Base	Mississippi	United States	39534
298	Singing River Hospital	Pascagoula	Mississippi	United States	39581
299	Southeast Missouri Hospital	Cape Girardeau	Missouri	United States	63701
300	Saint Francis Medical Center	Cape Girardeau	Missouri	United States	63703
301	Freeman Health System	Joplin	Missouri	United States	64804
302	Truman Medical Centers	Kansas City	Missouri	United States	64108
303	Saint Luke's Hospital of Kansas City	Kansas City	Missouri	United States	64111
304	Saint Joseph Health Center	Kansas City	Missouri	United States	64114
305	North Kansas City Hospital	Kansas City	Missouri	United States	64116
306	Heartland Hematology and Oncology Associates Incorporated	Kansas City	Missouri	United States	64118
307	Research Medical Center	Kansas City	Missouri	United States	64132
308	Saint Luke's East - Lee's Summit	Lee's Summit	Missouri	United States	64086
309	Liberty Radiation Oncology Center	Liberty	Missouri	United States	64068
310	Heartland Regional Medical Center	Saint Joseph	Missouri	United States	64506
311	Saint Joseph Oncology Inc	Saint Joseph	Missouri	United States	64507
312	Saint Louis Cancer and Breast Institute-South City	Saint Louis	Missouri	United States	63109
313	Mercy Hospital Saint Louis	Saint Louis	Missouri	United States	63141
314	Saint Louis-Cape Girardeau CCOP	Saint Louis	Missouri	United States	63141
315	Billings Clinic Cancer Center	Billings	Montana	United States	59101
316	Northern Rockies Radiation Oncology Center	Billings	Montana	United States	59101
317	Saint Vincent Healthcare	Billings	Montana	United States	59101
318	Montana Cancer Consortium NCORP	Billings	Montana	United States	59102
319	Saint Vincent Frontier Cancer Center	Billings	Montana	United States	59102
320	Bozeman Deaconess Hospital	Bozeman	Montana	United States	59715
321	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana	United States	59701
322	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana	United States	59405
323	Berdeaux, Donald MD (UIA Investigator)	Great Falls	Montana	United States	59405
324	Great Falls Clinic	Great Falls	Montana	United States	59405
325	Northern Montana Hospital	Havre	Montana	United States	59501
326	Saint Peter's Community Hospital	Helena	Montana	United States	59601
327	Glacier Oncology PLLC	Kalispell	Montana	United States	59901
328	Kalispell Medical Oncology	Kalispell	Montana	United States	59901
329	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
330	Montana Cancer Specialists	Missoula	Montana	United States	59802
331	Saint Patrick Hospital - Community Hospital	Missoula	Montana	United States	59802
332	Community Medical Hospital	Missoula	Montana	United States	59804
333	Guardian Oncology and Center for Wellness	Missoula	Montana	United States	59804
334	University Medical Center of Southern Nevada	Las Vegas	Nevada	United States	89102
335	Nevada Cancer Research Foundation NCORP	Las Vegas	Nevada	United States	89169
336	Cooper Hospital University Medical Center	Camden	New Jersey	United States	08103
337	CentraState Medical Center	Freehold	New Jersey	United States	07728
338	Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital	New Brunswick	New Jersey	United States	08903
339	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey	United States	08903
340	Rutgers New Jersey Medical School	Newark	New Jersey	United States	07101
341	Lovelace Medical Center-Saint Joseph Square	Albuquerque	New Mexico	United States	87102
342	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87102
343	Memorial Medical Center - Las Cruces	Las Cruces	New Mexico	United States	88011
344	San Juan Regional Medical Center	San Juan	New Mexico	United States	87401
345	Montefiore Medical Center-Wakefield Campus	Bronx	New York	United States	10466
346	Adirondack Cancer Center	Glens Falls	New York	United States	12801
347	Garnet Health Medical Center	Middletown	New York	United States	10940
348	NYU Winthrop Hospital	Mineola	New York	United States	11501
349	Mount Sinai Union Square	New York	New York	United States	10003
350	Mount Sinai West	New York	New York	United States	10019
351	Highland Hospital	Rochester	New York	United States	14620
352	University of Rochester	Rochester	New York	United States	14642
353	Mission Hospital	Asheville	North Carolina	United States	28801
354	Novant Health Presbyterian Medical Center	Charlotte	North Carolina	United States	28204
355	Wayne Memorial Hospital	Goldsboro	North Carolina	United States	27534
356	Margaret R Pardee Memorial Hospital	Hendersonville	North Carolina	United States	28791
357	Vidant Oncology-Kinston	Kinston	North Carolina	United States	28501
358	Rutherford Hospital	Rutherfordton	North Carolina	United States	28139
359	Southeast Clinical Oncology Research Consortium NCORP	Winston-Salem	North Carolina	United States	27104
360	Mid Dakota Clinic	Bismarck	North Dakota	United States	58501
361	Saint Alexius Medical Center	Bismarck	North Dakota	United States	58501
362	Sanford Bismarck Medical Center	Bismarck	North Dakota	United States	58501
363	Cleveland Clinic Cancer Center Beachwood	Beachwood	Ohio	United States	44122
364	Toledo Clinic Cancer Centers-Bowling Green	Bowling Green	Ohio	United States	43402
365	Case Western Reserve University	Cleveland	Ohio	United States	44106
366	MetroHealth Medical Center	Cleveland	Ohio	United States	44109
367	Cleveland Clinic Cancer Center/Fairview Hospital	Cleveland	Ohio	United States	44111
368	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
369	North Coast Cancer Care-Clyde	Clyde	Ohio	United States	43410
370	Grandview Hospital	Dayton	Ohio	United States	45405
371	Good Samaritan Hospital - Dayton	Dayton	Ohio	United States	45406
372	Miami Valley Hospital	Dayton	Ohio	United States	45409
373	Miami Valley Hospital North	Dayton	Ohio	United States	45415
374	Dayton Veterans Affairs Medical Center	Dayton	Ohio	United States	45428
375	Dayton NCI Community Oncology Research Program	Dayton	Ohio	United States	45459
376	Hematology Oncology Center Incorporated	Elyria	Ohio	United States	44035
377	Mercy Cancer Center-Elyria	Elyria	Ohio	United States	44035
378	Blanchard Valley Hospital	Findlay	Ohio	United States	45840
379	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio	United States	45005-1066
380	Wayne Hospital	Greenville	Ohio	United States	45331
381	Cleveland Clinic Cancer Center Independence	Independence	Ohio	United States	44131
382	Kettering Medical Center	Kettering	Ohio	United States	45429
383	Saint Rita's Medical Center	Lima	Ohio	United States	45801
384	Lima Memorial Hospital	Lima	Ohio	United States	45804
385	Saint Luke's Hospital	Maumee	Ohio	United States	43537
386	Toledo Clinic Cancer Centers-Maumee	Maumee	Ohio	United States	43537
387	Toledo Radiation Oncology at Northwest Ohio Onocolgy Center	Maumee	Ohio	United States	43537
388	Hillcrest Hospital Cancer Center	Mayfield Heights	Ohio	United States	44124
389	Fisher-Titus Medical Center	Norwalk	Ohio	United States	44857
390	Saint Charles Hospital	Oregon	Ohio	United States	43616
391	Toledo Clinic Cancer Centers-Oregon	Oregon	Ohio	United States	43616
392	University Hospitals Parma Medical Center	Parma	Ohio	United States	44129
393	North Coast Cancer Care	Sandusky	Ohio	United States	44870
394	ProMedica Flower Hospital	Sylvania	Ohio	United States	43560
395	Mercy Hospital of Tiffin	Tiffin	Ohio	United States	44883
396	ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital	Toledo	Ohio	United States	43606
397	Saint Vincent Mercy Medical Center	Toledo	Ohio	United States	43608
398	University of Toledo	Toledo	Ohio	United States	43614
399	Toledo Community Hospital Oncology Program CCOP	Toledo	Ohio	United States	43617
400	Mercy Health - Saint Anne Hospital	Toledo	Ohio	United States	43623
401	Toledo Clinic Cancer Centers-Toledo	Toledo	Ohio	United States	43623
402	Upper Valley Medical Center	Troy	Ohio	United States	45373
403	Fulton County Health Center	Wauseon	Ohio	United States	43567
404	Clinton Memorial Hospital	Wilmington	Ohio	United States	45177
405	Cleveland Clinic Wooster Family Health and Surgery Center	Wooster	Ohio	United States	44691
406	Greene Memorial Hospital	Xenia	Ohio	United States	45385
407	Clackamas Radiation Oncology Center	Clackamas	Oregon	United States	97015
408	Legacy Mount Hood Medical Center	Gresham	Oregon	United States	97030
409	Providence Milwaukie Hospital	Milwaukie	Oregon	United States	97222
410	Providence Newberg Medical Center	Newberg	Oregon	United States	97132
411	Providence Willamette Falls Medical Center	Oregon City	Oregon	United States	97045
412	Legacy Good Samaritan Hospital and Medical Center	Portland	Oregon	United States	97210
413	Providence Portland Medical Center	Portland	Oregon	United States	97213
414	Adventist Medical Center	Portland	Oregon	United States	97216
415	Providence Saint Vincent Medical Center	Portland	Oregon	United States	97225
416	Compass Oncology Rose Quarter	Portland	Oregon	United States	97227
417	Legacy Emanuel Hospital and Health Center	Portland	Oregon	United States	97227
418	Legacy Meridian Park Hospital	Tualatin	Oregon	United States	97062
419	Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania	United States	18103
420	Butler Memorial Hospital	Butler	Pennsylvania	United States	16001
421	Geisinger Medical Center	Danville	Pennsylvania	United States	17822
422	Oncology Hematology Associates of Northern Pennsylvania	DuBois	Pennsylvania	United States	15801
423	Geisinger Medical Center-Cancer Center Hazleton	Hazleton	Pennsylvania	United States	18201
424	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania	United States	17033-0850
425	Lancaster General Hospital	Lancaster	Pennsylvania	United States	17602
426	Pennsylvania Hospital	Philadelphia	Pennsylvania	United States	19107
427	Geisinger Medical Group	State College	Pennsylvania	United States	16801
428	Mount Nittany Medical Center	State College	Pennsylvania	United States	16803
429	Associates In Hematology Oncology PC-Upland	Upland	Pennsylvania	United States	19013
430	Jennersville Regional Hospital	West Grove	Pennsylvania	United States	19390
431	Reading Hospital	West Reading	Pennsylvania	United States	19611
432	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania	United States	18711
433	Geisinger South Wilkes-Barre	Wilkes-Barre	Pennsylvania	United States	18765
434	Hematology and Oncology Associates of Rhode Island Inc	Cranston	Rhode Island	United States	02920
435	Memorial Hospital of Rhode Island	Pawtucket	Rhode Island	United States	02860
436	Kent Hospital	Warwick	Rhode Island	United States	02886
437	AnMed Health Hospital	Anderson	South Carolina	United States	29621
438	Spartanburg Medical Center	Spartanburg	South Carolina	United States	29303
439	Rapid City Regional Hospital	Rapid City	South Dakota	United States	57701
440	Sanford Cancer Center Oncology Clinic	Sioux Falls	South Dakota	United States	57104
441	Avera Cancer Institute	Sioux Falls	South Dakota	United States	57105
442	Medical X-Ray Center	Sioux Falls	South Dakota	United States	57105
443	Avera McKennan Hospital and University Health Center	Sioux Falls	South Dakota	United States	57117-5045
444	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota	United States	57117-5134
445	Erlanger Medical Center	Chattanooga	Tennessee	United States	37403
446	Jackson-Madison County General Hospital	Jackson	Tennessee	United States	38301
447	The Jackson Clinic PA	Jackson	Tennessee	United States	38301
448	Wellmont Holston Valley Hospital and Medical Center	Kingsport	Tennessee	United States	37660
449	University of Tennessee Health Science Center	Memphis	Tennessee	United States	38163
450	The Don and Sybil Harrington Cancer Center	Amarillo	Texas	United States	79106
451	Brooke Army Medical Center	Fort Sam Houston	Texas	United States	78234
452	Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center	Houston	Texas	United States	77030
453	Baylor Saint Luke's Medical Center	Houston	Texas	United States	77030
454	Ben Taub General Hospital	Houston	Texas	United States	77030
455	Houston Methodist Hospital	Houston	Texas	United States	77030
456	M D Anderson Cancer Center	Houston	Texas	United States	77030
457	Michael E DeBakey VA Medical Center	Houston	Texas	United States	77030
458	Wilford Hall Medical Center	Lackland Air Force Base	Texas	United States	78236
459	Danville Regional Medical Center	Danville	Virginia	United States	24541
460	Fredericksburg Oncology Inc	Fredericksburg	Virginia	United States	22401
461	Sovah Health Martinsville	Martinsville	Virginia	United States	24115
462	Southwest VA Regional Cancer Center	Norton	Virginia	United States	24273
463	Virginia Mason Medical Center	Seattle	Washington	United States	98101
464	PeaceHealth Southwest Medical Center	Vancouver	Washington	United States	98664
465	Compass Oncology Vancouver	Vancouver	Washington	United States	98684
466	Legacy Salmon Creek Hospital	Vancouver	Washington	United States	98686
467	Wheeling Hospital/Schiffler Cancer Center	Wheeling	West Virginia	United States	26003
468	Aurora Cancer Care-Southern Lakes VLCC	Burlington	Wisconsin	United States	53105
469	Marshfield Clinic-Chippewa Center	Chippewa Falls	Wisconsin	United States	54729
470	HSHS Sacred Heart Hospital	Eau Claire	Wisconsin	United States	54701
471	Marshfield Clinic Cancer Center at Sacred Heart	Eau Claire	Wisconsin	United States	54701
472	Green Bay Oncology at Saint Vincent Hospital	Green Bay	Wisconsin	United States	54301-3526
473	Saint Vincent Hospital Cancer Center Green Bay	Green Bay	Wisconsin	United States	54301
474	Green Bay Oncology Limited at Saint Mary's Hospital	Green Bay	Wisconsin	United States	54303
475	Saint Vincent Hospital Cancer Center at Saint Mary's	Green Bay	Wisconsin	United States	54303
476	Aurora BayCare Medical Center	Green Bay	Wisconsin	United States	54311
477	UW Cancer Center Johnson Creek	Johnson Creek	Wisconsin	United States	53038
478	Gundersen Lutheran Medical Center	La Crosse	Wisconsin	United States	54601
479	Mayo Clinic Health System-Franciscan Healthcare	La Crosse	Wisconsin	United States	54601
480	Marshfield Clinic - Ladysmith Center	Ladysmith	Wisconsin	United States	54848
481	University of Wisconsin Carbone Cancer Center	Madison	Wisconsin	United States	53792
482	Holy Family Memorial Hospital	Manitowoc	Wisconsin	United States	54221
483	Aurora Bay Area Medical Group-Marinette	Marinette	Wisconsin	United States	54143
484	Bay Area Medical Center	Marinette	Wisconsin	United States	54143
485	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin	United States	54449
486	Marshfield Medical Center	Marshfield	Wisconsin	United States	54449
487	Ascension Southeast Wisconsin Hospital - Saint Joseph Campus	Milwaukee	Wisconsin	United States	53210
488	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin	United States	54548
489	Saint Vincent Hospital Cancer Center at Oconto Falls	Oconto Falls	Wisconsin	United States	54154
490	Ascension Saint Mary's Hospital	Rhinelander	Wisconsin	United States	54501
491	Marshfield Medical Center-Rice Lake	Rice Lake	Wisconsin	United States	54868
492	HSHS Saint Nicholas Hospital	Sheboygan	Wisconsin	United States	53081
493	Vince Lombardi Cancer Clinic-Sheboygan	Sheboygan	Wisconsin	United States	53081
494	Ascension Saint Michael's Hospital	Stevens Point	Wisconsin	United States	54481
495	Saint Vincent Hospital Cancer Center at Sturgeon Bay	Sturgeon Bay	Wisconsin	United States	54235-1495
496	Green Bay Oncology - Sturgeon Bay	Sturgeon Bay	Wisconsin	United States	54235
497	Aurora Medical Center in Summit	Summit	Wisconsin	United States	53066
498	Vince Lombardi Cancer Clinic-Two Rivers	Two Rivers	Wisconsin	United States	54241
499	Ascension Saint Clare's Hospital	Weston	Wisconsin	United States	54476
500	Marshfield Medical Center - Weston	Weston	Wisconsin	United States	54476
501	Marshfield Clinic - Wisconsin Rapids Center	Wisconsin Rapids	Wisconsin	United States	54494
502	Rocky Mountain Oncology	Casper	Wyoming	United States	82609
503	Welch Cancer Center	Sheridan	Wyoming	United States	82801
504	San Juan City Hospital	San Juan		Puerto Rico	00936
505	King Faisal Specialist Hospital and Research Centre	Riyadh		Saudi Arabia	11211

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Brian M Durie, Southwest Oncology Group

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive.

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00644228
• Other Study ID Numbers: NCI-2009-00798; NCI-2009-00798; SWOG-S0777; S0777; CDR0000590321; S0777; S0777; U10CA180888; U10CA032102
• First Posted: Mar 26, 2008
• Last Update Posted: Jun 29, 2022
• Last Verified: Mar 1, 2022

• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Dexamethasone; Dexamethasone acetate; Lenalidomide; Bortezomib; Ichthammol; BB 1101

Study Results

Participant Flow

Arm/Group Title	Arm I (Dexamethasone and Lenalidomide)	Arm II (Dexamethasone, Lenalidomide, Bortezomib)
Arm/Group Description	Patients receive dexamethasone PO QD on days 1, 8, 15, and 22 and lenalidomide PO QD on days 1-21. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Dexamethasone: Given PO Laboratory Biomarker Analysis: Optional correlative studies Lenalidomide: Given PO	Patients receive dexamethasone PO QD on days 1, 2, 4, 5, 8, 9, 11, and 12; lenalidomide PO QD on days 1-14; and bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. Bortezomib: Given IV Dexamethasone: Given PO Laboratory Biomarker Analysis: Optional correlative studies Lenalidomide: Given PO
Period Title: Randomization & Eligibility
STARTED	261	264
Eligible and Analyzable	229	242
COMPLETED	229	242
NOT COMPLETED	32	22
Period Title: Randomization & Eligibility
STARTED	229	242
COMPLETED	146	137
NOT COMPLETED	83	105
Period Title: Randomization & Eligibility
STARTED	143	135
COMPLETED	0	0
NOT COMPLETED	143	135

Baseline Characteristics

Arm/Group Title	Arm I (Dexamethasone and Lenalidomide)	Arm II (Dexamethasone, Lenalidomide, Bortezomib)	Total
Arm/Group Description	Patients receive dexamethasone PO QD on days 1, 8, 15, and 22 and lenalidomide PO QD on days 1-21. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Dexamethasone: Given PO Laboratory Biomarker Analysis: Optional correlative studies Lenalidomide: Given PO	Patients receive dexamethasone PO QD on days 1, 2, 4, 5, 8, 9, 11, and 12; lenalidomide PO QD on days 1-14; and bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. Bortezomib: Given IV Dexamethasone: Given PO Laboratory Biomarker Analysis: Optional correlative studies Lenalidomide: Given PO	Total of all reporting groups
Overall Participants	229	242	471
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	120 52.4%	149 61.6%	269 57.1%
>=65 years	109 47.6%	93 38.4%	202 42.9%
Sex: Female, Male (Count of Participants)
Female	107 46.7%	89 36.8%	196 41.6%
Male	122 53.3%	153 63.2%	275 58.4%
ISS Stage (Count of Participants)
ISS Stage I or II	150 65.5%	164 67.8%	314 66.7%
ISS Stage III	79 34.5%	78 32.2%	157 33.3%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival
Description	Unstratified median progression-free survival in months.
Time Frame	From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause, assessed up to 6 years

Outcome Measure Data

Analysis Population Description

All eligible and analyzable patients are included. An analyzable patient is one who provided valid consent and who did not withdraw consent prior to initiating treatment.

Arm/Group Title	Arm I (Dexamethasone and Lenalidomide)	Arm II (Dexamethasone, Lenalidomide, Bortezomib)
Arm/Group Description	Patients receive dexamethasone PO QD on days 1, 8, 15, and 22 and lenalidomide PO QD on days 1-21. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Dexamethasone: Given PO Laboratory Biomarker Analysis: Optional correlative studies Lenalidomide: Given PO	Patients receive dexamethasone PO QD on days 1, 2, 4, 5, 8, 9, 11, and 12; lenalidomide PO QD on days 1-14; and bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. Bortezomib: Given IV Dexamethasone: Given PO Laboratory Biomarker Analysis: Optional correlative studies Lenalidomide: Given PO
Measure Participants	229	242
Median (95% Confidence Interval) [Months]	30	43

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Dexamethasone and Lenalidomide), Arm II (Dexamethasone, Lenalidomide, Bortezomib)
	Comments	With four years of patient accrual and two and a half years of follow-up, 220 patients per arm yields 87% power to detect an increase of PFS of 50%, from a median of 3 years to 4.5 years, which corresponds to a hazard ratio of 1.5. These calculations are based on a one-sided stratified log-rank test at level 0.025 with two interim analyses. The final analysis will be carried out at the 0.02 significance level to allow for two interim analyses at the 0.0025 significance level.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0018
	Comments	The p-value is from a one-sided, stratified log-rank test. Stratification factors include those factors by which patients were randomized: intent to transplant (yes vs no) and ISS Stage (I vs II vs III).
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.712
	Confidence Interval	(2-Sided) 96%; 0.560 to 0.906
	Parameter Dispersion	Type: Value:
	Estimation Comments	The hazard ratio compares Bortezomib/Lenalidomide/Dexamethasone against Lenalidomide/Dexamethasone.

2. Secondary Outcome

Title	Overall Survival
Description	Unstratified median overall survival in months.
Time Frame	Up to 6 years

Outcome Measure Data

Analysis Population Description

All eligible and analyzable patients are included. An analyzable patient is one who provided valid consent and who did not withdraw consent prior to initiating treatment.

Arm/Group Title	Arm I (Dexamethasone and Lenalidomide)	Arm II (Dexamethasone, Lenalidomide, Bortezomib)
Arm/Group Description	Patients receive dexamethasone PO QD on days 1, 8, 15, and 22 and lenalidomide PO QD on days 1-21. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Dexamethasone: Given PO Laboratory Biomarker Analysis: Optional correlative studies Lenalidomide: Given PO	Patients receive dexamethasone PO QD on days 1, 2, 4, 5, 8, 9, 11, and 12; lenalidomide PO QD on days 1-14; and bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. Bortezomib: Given IV Dexamethasone: Given PO Laboratory Biomarker Analysis: Optional correlative studies Lenalidomide: Given PO
Measure Participants	229	242
Median (95% Confidence Interval) [Months]	64	75

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Dexamethasone and Lenalidomide), Arm II (Dexamethasone, Lenalidomide, Bortezomib)
	Comments	Overall survival will be compared between the two treatment arms using a stratified log-rank test.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0250
	Comments	The p-value is based on a two-sided, stratified log rank test. Stratification factors include those factors by which patients were randomized: intent to transplant (yes vs no) and ISS Stage (I vs II vs III).
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.709
	Confidence Interval	(2-Sided) 95%; 0.524 to 0.959
	Parameter Dispersion	Type: Value:
	Estimation Comments	The hazard ratio compares Bortezomib/Lenalidomide/Dexamethasone against Lenalidomide/Dexamethasone.

3. Secondary Outcome

Title	Response Rates ()
Description	The response rate was calculated as the number of patients with documented confirmed partial response (PR) or better, which includes confirmed/unconfirmed stringent complete response (sCR), confirmed/unconfirmed complete response (CR), confirmed/unconfirmed very good partial response (VGPR), or confirmed partial response (PR), as best response divided by the total number of evaluable patients, in each arm. Patients with measurable disease, as defined in the protocol, are evaluable. Response rates were compared between the two treatment arms using a stratified Cochran-Mantel-Haenszel test. Response designations were based on the International Uniform Response Criteria for Multiple Myeloma. Due to the complexity of these criteria, the details of these criteria have been omitted.
Time Frame	Up to 6 years

Outcome Measure Data

Analysis Population Description

All eligible, analyzable patients are included.

Arm/Group Title	Arm I (Dexamethasone and Lenalidomide)	Arm II (Dexamethasone, Lenalidomide, Bortezomib)
Arm/Group Description	Patients receive dexamethasone PO QD on days 1, 8, 15, and 22 and lenalidomide PO QD on days 1-21. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Dexamethasone: Given PO Laboratory Biomarker Analysis: Optional correlative studies Lenalidomide: Given PO	Patients receive dexamethasone PO QD on days 1, 2, 4, 5, 8, 9, 11, and 12; lenalidomide PO QD on days 1-14; and bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. Bortezomib: Given IV Dexamethasone: Given PO Laboratory Biomarker Analysis: Optional correlative studies Lenalidomide: Given PO
Measure Participants	229	242
Count of Participants [Participants]	153 66.8%	176 72.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Dexamethasone and Lenalidomide), Arm II (Dexamethasone, Lenalidomide, Bortezomib)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.20
	Comments	The p-value is based on a stratified Cochran-Mantel-Haenszel test. Stratification factors include those factors by which patients were randomized: intent to transplant (yes vs no) and ISS Stage (I vs II vs III).
	Method	Cochran-Mantel-Haenszel
	Comments

Adverse Events

Adverse Event Reporting Description	The number at risk excludes patients who went off study prior to starting treatment and were thus not evaluated for toxicity. The adverse events reported here are current up through the time of upload of these data.
Arm/Group Title	Arm I (Dexamethasone and Lenalidomide)		Arm II (Dexamethasone, Lenalidomide, Bortezomib)
Arm/Group Description	Patients receive dexamethasone PO QD on days 1, 8, 15, and 22 and lenalidomide PO QD on days 1-21. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Dexamethasone: Given PO Laboratory Biomarker Analysis: Optional correlative studies Lenalidomide: Given PO		Patients receive dexamethasone PO QD on days 1, 2, 4, 5, 8, 9, 11, and 12; lenalidomide PO QD on days 1-14; and bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. Bortezomib: Given IV Dexamethasone: Given PO Laboratory Biomarker Analysis: Optional correlative studies Lenalidomide: Given PO
All Cause Mortality
	Arm I (Dexamethasone and Lenalidomide)		Arm II (Dexamethasone, Lenalidomide, Bortezomib)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm I (Dexamethasone and Lenalidomide)		Arm II (Dexamethasone, Lenalidomide, Bortezomib)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	105/222 (47.3%)		124/237 (52.3%)
Blood and lymphatic system disorders
Febrile neutropenia	5/222 (2.3%)		0/237 (0%)
Hemoglobin	24/222 (10.8%)		13/237 (5.5%)
Hemolysis	1/222 (0.5%)		0/237 (0%)
Cardiac disorders
Cardiac Arrhythmia-Other	0/222 (0%)		1/237 (0.4%)
Cardiac General-Other	1/222 (0.5%)		3/237 (1.3%)
Cardiac-ischemia/infarction	4/222 (1.8%)		1/237 (0.4%)
Conduction abnormality NOS	1/222 (0.5%)		1/237 (0.4%)
Left ventricular diastolic dysfunction	4/222 (1.8%)		1/237 (0.4%)
Left ventricular systolic dysfunction	4/222 (1.8%)		0/237 (0%)
Pain - Cardiac/heart	2/222 (0.9%)		0/237 (0%)
SVT and nodal arrhythmia - Atrial fibrillation	5/222 (2.3%)		5/237 (2.1%)
SVT and nodal arrhythmia - Atrial flutter	1/222 (0.5%)		0/237 (0%)
SVT and nodal arrhythmia - Sinus bradycardia	1/222 (0.5%)		2/237 (0.8%)
SVT and nodal arrhythmia - Sinus tachycardia	1/222 (0.5%)		0/237 (0%)
Valvular heart disease	1/222 (0.5%)		0/237 (0%)
Endocrine disorders
Thyroid function, high	0/222 (0%)		1/237 (0.4%)
Eye disorders
Cataract	1/222 (0.5%)		0/237 (0%)
Dry eye syndrome	0/222 (0%)		1/237 (0.4%)
Ocular/Visual-Other	0/222 (0%)		1/237 (0.4%)
Ophthalmoplegia/diplopia (double vision)	0/222 (0%)		1/237 (0.4%)
Vision-blurred vision	0/222 (0%)		1/237 (0.4%)
Gastrointestinal disorders
Colitis	0/222 (0%)		2/237 (0.8%)
Constipation	0/222 (0%)		2/237 (0.8%)
Diarrhea	6/222 (2.7%)		10/237 (4.2%)
Dry mouth/salivary gland (xerostomia)	1/222 (0.5%)		1/237 (0.4%)
Dysphagia (difficulty swallowing)	1/222 (0.5%)		1/237 (0.4%)
Gastritis (including bile reflux gastritis)	1/222 (0.5%)		0/237 (0%)
Gastrointestinal-Other	0/222 (0%)		2/237 (0.8%)
Hemorrhage, GI - Lower GI NOS	1/222 (0.5%)		4/237 (1.7%)
Hemorrhage, GI - Rectum	2/222 (0.9%)		1/237 (0.4%)
Hemorrhage, GI - Stomach	0/222 (0%)		1/237 (0.4%)
Hemorrhage, GI - Upper GI NOS	0/222 (0%)		1/237 (0.4%)
Hemorrhage, GI - Varices (rectal)	1/222 (0.5%)		0/237 (0%)
Ileus, GI (functional obstruction of bowel)	0/222 (0%)		1/237 (0.4%)
Nausea	2/222 (0.9%)		2/237 (0.8%)
Obstruction, GI - Colon	1/222 (0.5%)		0/237 (0%)
Obstruction, GI - Small bowel NOS	0/222 (0%)		3/237 (1.3%)
Obstruction, GI - Stomach	0/222 (0%)		1/237 (0.4%)
Pain - Abdomen NOS	2/222 (0.9%)		5/237 (2.1%)
Perforation, GI - Colon	1/222 (0.5%)		1/237 (0.4%)
Typhlitis (cecal inflammation)	0/222 (0%)		1/237 (0.4%)
Vomiting	1/222 (0.5%)		3/237 (1.3%)
General disorders
Death - Multi-organ failure	0/222 (0%)		1/237 (0.4%)
Death not associated with CTCAE term - Death NOS	1/222 (0.5%)		4/237 (1.7%)
Edema: limb	1/222 (0.5%)		2/237 (0.8%)
Extremity-lower (gait/walking)	1/222 (0.5%)		1/237 (0.4%)
Fatigue (asthenia, lethargy, malaise)	5/222 (2.3%)		8/237 (3.4%)
Fever in absence of neutropenia, ANC lt1.0x10e9/L	1/222 (0.5%)		0/237 (0%)
Flu-like syndrome	0/222 (0%)		2/237 (0.8%)
Pain - Chest/thorax NOS	0/222 (0%)		3/237 (1.3%)
Pain - Pain NOS	1/222 (0.5%)		3/237 (1.3%)
Pain-Other	0/222 (0%)		1/237 (0.4%)
Sudden death	1/222 (0.5%)		1/237 (0.4%)
Hepatobiliary disorders
Cholecystitis	0/222 (0%)		2/237 (0.8%)
Hepatobiliary/Pancreas-Other	1/222 (0.5%)		0/237 (0%)
Liver dysfunction/failure (clinical)	2/222 (0.9%)		2/237 (0.8%)
Pain - Gallbladder	1/222 (0.5%)		0/237 (0%)
Immune system disorders
Allergic reaction/hypersensitivity	1/222 (0.5%)		1/237 (0.4%)
Infections and infestations
Colitis, infectious (e.g., Clostridium difficile)	1/222 (0.5%)		2/237 (0.8%)
Inf (clin/microbio) w/Gr 3-4 neuts - Blood	1/222 (0.5%)		0/237 (0%)
Inf (clin/microbio) w/Gr 3-4 neuts - Bronchus	1/222 (0.5%)		0/237 (0%)
Inf (clin/microbio) w/Gr 3-4 neuts - Cecum	1/222 (0.5%)		0/237 (0%)
Inf (clin/microbio) w/Gr 3-4 neuts - Lung	3/222 (1.4%)		3/237 (1.3%)
Inf (clin/microbio) w/Gr 3-4 neuts - UTI	1/222 (0.5%)		0/237 (0%)
Inf (clin/microbio) w/Gr 3-4 neuts - Upper airway	1/222 (0.5%)		0/237 (0%)
Inf w/normal ANC or Gr 1-2 neutrophils - Bladder	1/222 (0.5%)		0/237 (0%)
Inf w/normal ANC or Gr 1-2 neutrophils - Blood	0/222 (0%)		2/237 (0.8%)
Inf w/normal ANC or Gr 1-2 neutrophils - Catheter	0/222 (0%)		1/237 (0.4%)
Inf w/normal ANC or Gr 1-2 neutrophils - Colon	1/222 (0.5%)		0/237 (0%)
Inf w/normal ANC or Gr 1-2 neutrophils - Lung	6/222 (2.7%)		8/237 (3.4%)
Inf w/normal ANC or Gr 1-2 neutrophils - UTI	1/222 (0.5%)		5/237 (2.1%)
Inf w/normal ANC or Gr 1-2 neutrophils - Wound	2/222 (0.9%)		0/237 (0%)
Infection with unknown ANC - Anal/perianal	0/222 (0%)		1/237 (0.4%)
Infection with unknown ANC - Blood	3/222 (1.4%)		4/237 (1.7%)
Infection with unknown ANC - Bone (osteomyelitis)	1/222 (0.5%)		0/237 (0%)
Infection with unknown ANC - Bronchus	0/222 (0%)		1/237 (0.4%)
Infection with unknown ANC - Catheter-related	0/222 (0%)		1/237 (0.4%)
Infection with unknown ANC - Eye NOS	1/222 (0.5%)		0/237 (0%)
Infection with unknown ANC - Heart (endocarditis)	0/222 (0%)		1/237 (0.4%)
Infection with unknown ANC - Joint	1/222 (0.5%)		1/237 (0.4%)
Infection with unknown ANC - Lung (pneumonia)	15/222 (6.8%)		10/237 (4.2%)
Infection with unknown ANC - Meninges (meningitis)	1/222 (0.5%)		0/237 (0%)
Infection with unknown ANC - Mucosa	0/222 (0%)		1/237 (0.4%)
Infection with unknown ANC - Pharynx	1/222 (0.5%)		0/237 (0%)
Infection with unknown ANC - Sinus	1/222 (0.5%)		0/237 (0%)
Infection with unknown ANC - Skin (cellulitis)	0/222 (0%)		4/237 (1.7%)
Infection with unknown ANC - Upper airway NOS	0/222 (0%)		2/237 (0.8%)
Infection with unknown ANC - Urinary tract NOS	2/222 (0.9%)		2/237 (0.8%)
Infection-Other	5/222 (2.3%)		4/237 (1.7%)
Injury, poisoning and procedural complications
Fracture	4/222 (1.8%)		6/237 (2.5%)
Thrombosis/embolism (vascular access-related)	1/222 (0.5%)		3/237 (1.3%)
Wound complication, non-infectious	0/222 (0%)		1/237 (0.4%)
Investigations
ALT, SGPT (serum glutamic pyruvic transaminase)	2/222 (0.9%)		3/237 (1.3%)
AST, SGOT	2/222 (0.9%)		1/237 (0.4%)
Alkaline phosphatase	1/222 (0.5%)		1/237 (0.4%)
Bilirubin (hyperbilirubinemia)	1/222 (0.5%)		1/237 (0.4%)
Cardiac troponin I (cTnI)	0/222 (0%)		1/237 (0.4%)
Creatinine	9/222 (4.1%)		7/237 (3%)
INR (of prothrombin time)	1/222 (0.5%)		3/237 (1.3%)
Leukocytes (total WBC)	2/222 (0.9%)		3/237 (1.3%)
Lymphopenia	0/222 (0%)		5/237 (2.1%)
Metabolic/Laboratory-Other	0/222 (0%)		1/237 (0.4%)
Neutrophils/granulocytes (ANC/AGC)	2/222 (0.9%)		5/237 (2.1%)
PTT (Partial thromboplastin time)	0/222 (0%)		1/237 (0.4%)
Platelets	5/222 (2.3%)		13/237 (5.5%)
Weight loss	1/222 (0.5%)		2/237 (0.8%)
Metabolism and nutrition disorders
Acidosis (metabolic or respiratory)	0/222 (0%)		1/237 (0.4%)
Albumin, serum-low (hypoalbuminemia)	0/222 (0%)		1/237 (0.4%)
Anorexia	2/222 (0.9%)		5/237 (2.1%)
Calcium, serum-high (hypercalcemia)	2/222 (0.9%)		2/237 (0.8%)
Calcium, serum-low (hypocalcemia)	6/222 (2.7%)		5/237 (2.1%)
Dehydration	9/222 (4.1%)		17/237 (7.2%)
Glucose, serum-high (hyperglycemia)	6/222 (2.7%)		6/237 (2.5%)
Glucose, serum-low (hypoglycemia)	2/222 (0.9%)		1/237 (0.4%)
Phosphate, serum-low (hypophosphatemia)	1/222 (0.5%)		2/237 (0.8%)
Potassium, serum-low (hypokalemia)	2/222 (0.9%)		12/237 (5.1%)
Sodium, serum-high (hypernatremia)	1/222 (0.5%)		0/237 (0%)
Sodium, serum-low (hyponatremia)	3/222 (1.4%)		5/237 (2.1%)
Tumor lysis syndrome	2/222 (0.9%)		2/237 (0.8%)
Uric acid, serum-high (hyperuricemia)	1/222 (0.5%)		0/237 (0%)
Musculoskeletal and connective tissue disorders
Arthritis (non-septic)	1/222 (0.5%)		2/237 (0.8%)
Joint-effusion	0/222 (0%)		1/237 (0.4%)
Muscle weakness, not d/t neuropathy - Extrem-lower	1/222 (0.5%)		4/237 (1.7%)
Muscle weakness, not d/t neuropathy - body/general	3/222 (1.4%)		11/237 (4.6%)
Musculoskeletal/Soft Tissue-Other	1/222 (0.5%)		3/237 (1.3%)
Osteonecrosis (avascular necrosis)	2/222 (0.9%)		1/237 (0.4%)
Pain - Back	4/222 (1.8%)		4/237 (1.7%)
Pain - Bone	3/222 (1.4%)		1/237 (0.4%)
Pain - Chest wall	1/222 (0.5%)		0/237 (0%)
Pain - Extremity-limb	1/222 (0.5%)		2/237 (0.8%)
Pain - Joint	1/222 (0.5%)		1/237 (0.4%)
Pain - Muscle	1/222 (0.5%)		0/237 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Death - Disease progression NOS	2/222 (0.9%)		0/237 (0%)
Myelodysplasia	1/222 (0.5%)		0/237 (0%)
Secondary Malignancy-poss rel to cancer Tx	3/222 (1.4%)		2/237 (0.8%)
Nervous system disorders
CNS cerebrovascular ischemia	3/222 (1.4%)		1/237 (0.4%)
Cognitive disturbance	2/222 (0.9%)		0/237 (0%)
Dizziness	0/222 (0%)		4/237 (1.7%)
Encephalopathy	3/222 (1.4%)		1/237 (0.4%)
Hemorrhage, CNS	1/222 (0.5%)		0/237 (0%)
Neurology-Other	3/222 (1.4%)		1/237 (0.4%)
Neuropathy: motor	1/222 (0.5%)		2/237 (0.8%)
Neuropathy: sensory	2/222 (0.9%)		7/237 (3%)
Ocular/Visual-Other	0/222 (0%)		1/237 (0.4%)
Pain - Head/headache	0/222 (0%)		1/237 (0.4%)
Seizure	0/222 (0%)		2/237 (0.8%)
Somnolence/depressed level of consciousness	3/222 (1.4%)		2/237 (0.8%)
Syncope (fainting)	5/222 (2.3%)		12/237 (5.1%)
Taste alteration (dysgeusia)	1/222 (0.5%)		0/237 (0%)
Tremor	0/222 (0%)		2/237 (0.8%)
Psychiatric disorders
Confusion	5/222 (2.3%)		3/237 (1.3%)
Mood alteration - depression	0/222 (0%)		1/237 (0.4%)
Psychosis (hallucinations/delusions)	1/222 (0.5%)		0/237 (0%)
Renal and urinary disorders
Fistula, GU - Bladder	0/222 (0%)		1/237 (0.4%)
Glomerular filtration rate	1/222 (0.5%)		1/237 (0.4%)
Hemorrhage, GU - Urinary NOS	1/222 (0.5%)		0/237 (0%)
Incontinence, urinary	1/222 (0.5%)		0/237 (0%)
Renal failure	13/222 (5.9%)		3/237 (1.3%)
Renal/Genitourinary-Other	2/222 (0.9%)		2/237 (0.8%)
Urinary retention (including neurogenic bladder)	1/222 (0.5%)		1/237 (0.4%)
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome (ARDS)	0/222 (0%)		2/237 (0.8%)
Bronchospasm, wheezing	1/222 (0.5%)		0/237 (0%)
Cough	1/222 (0.5%)		1/237 (0.4%)
Dyspnea (shortness of breath)	4/222 (1.8%)		9/237 (3.8%)
Hypoxia	4/222 (1.8%)		6/237 (2.5%)
Mucositis/stomatitis (clinical exam) - Pharynx	1/222 (0.5%)		0/237 (0%)
Pain - Pleura	0/222 (0%)		1/237 (0.4%)
Pleural effusion (non-malignant)	2/222 (0.9%)		0/237 (0%)
Pneumonitis/pulmonary infiltrates	3/222 (1.4%)		6/237 (2.5%)
Pulmonary/Upper Respiratory-Other	4/222 (1.8%)		2/237 (0.8%)
Skin and subcutaneous tissue disorders
Rash/desquamation	2/222 (0.9%)		1/237 (0.4%)
Skin breakdown/decubitus ulcer	1/222 (0.5%)		0/237 (0%)
Urticaria (hives, welts, wheals)	0/222 (0%)		1/237 (0.4%)
Vascular disorders
Hypertension	2/222 (0.9%)		4/237 (1.7%)
Hypotension	2/222 (0.9%)		16/237 (6.8%)
Thrombosis/thrombus/embolism	9/222 (4.1%)		8/237 (3.4%)
Other (Not Including Serious) Adverse Events
	Arm I (Dexamethasone and Lenalidomide)		Arm II (Dexamethasone, Lenalidomide, Bortezomib)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	209/222 (94.1%)		232/237 (97.9%)
Blood and lymphatic system disorders
Hemoglobin	162/222 (73%)		172/237 (72.6%)
Ear and labyrinth disorders
Tinnitus	19/222 (8.6%)		9/237 (3.8%)
Eye disorders
Cataract	14/222 (6.3%)		19/237 (8%)
Dry eye syndrome	13/222 (5.9%)		19/237 (8%)
Vision-blurred vision	41/222 (18.5%)		53/237 (22.4%)
Gastrointestinal disorders
Constipation	119/222 (53.6%)		141/237 (59.5%)
Diarrhea	99/222 (44.6%)		113/237 (47.7%)
Distention/bloating, abdominal	8/222 (3.6%)		13/237 (5.5%)
Dry mouth/salivary gland (xerostomia)	27/222 (12.2%)		30/237 (12.7%)
Flatulence	24/222 (10.8%)		22/237 (9.3%)
Gastrointestinal-Other	12/222 (5.4%)		10/237 (4.2%)
Heartburn/dyspepsia	43/222 (19.4%)		58/237 (24.5%)
Mucositis/stomatitis (clinical exam) - Oral cavity	20/222 (9%)		16/237 (6.8%)
Mucositis/stomatitis (functional/symp) - Oral cav	11/222 (5%)		17/237 (7.2%)
Nausea	88/222 (39.6%)		105/237 (44.3%)
Pain - Abdomen NOS	33/222 (14.9%)		43/237 (18.1%)
Pain - Dental/teeth/peridontal	13/222 (5.9%)		6/237 (2.5%)
Vomiting	38/222 (17.1%)		47/237 (19.8%)
General disorders
Edema: limb	90/222 (40.5%)		114/237 (48.1%)
Extremity-lower (gait/walking)	15/222 (6.8%)		15/237 (6.3%)
Fatigue (asthenia, lethargy, malaise)	178/222 (80.2%)		191/237 (80.6%)
Fever in absence of neutropenia, ANC lt1.0x10e9/L	37/222 (16.7%)		48/237 (20.3%)
Pain - Chest/thorax NOS	11/222 (5%)		15/237 (6.3%)
Pain-Other	36/222 (16.2%)		43/237 (18.1%)
Rigors/chills	28/222 (12.6%)		34/237 (14.3%)
Infections and infestations
Inf w/normal ANC or Gr 1-2 neutrophils - Lung	21/222 (9.5%)		20/237 (8.4%)
Inf w/normal ANC or Gr 1-2 neutrophils - Skin	15/222 (6.8%)		11/237 (4.6%)
Inf w/normal ANC or Gr 1-2 neutrophils - Up airway	17/222 (7.7%)		20/237 (8.4%)
Infection-Other	13/222 (5.9%)		29/237 (12.2%)
Injury, poisoning and procedural complications
Bruising (in absence of Gr 3-4 thrombocytopenia)	23/222 (10.4%)		24/237 (10.1%)
Fracture	8/222 (3.6%)		15/237 (6.3%)
Investigations
ALT, SGPT (serum glutamic pyruvic transaminase)	59/222 (26.6%)		70/237 (29.5%)
AST, SGOT	50/222 (22.5%)		71/237 (30%)
Alkaline phosphatase	50/222 (22.5%)		68/237 (28.7%)
Bilirubin (hyperbilirubinemia)	23/222 (10.4%)		34/237 (14.3%)
Creatinine	78/222 (35.1%)		69/237 (29.1%)
Leukocytes (total WBC)	137/222 (61.7%)		124/237 (52.3%)
Lymphopenia	72/222 (32.4%)		76/237 (32.1%)
Metabolic/Laboratory-Other	20/222 (9%)		24/237 (10.1%)
Neutrophils/granulocytes (ANC/AGC)	117/222 (52.7%)		91/237 (38.4%)
Platelets	130/222 (58.6%)		144/237 (60.8%)
Weight gain	22/222 (9.9%)		17/237 (7.2%)
Weight loss	59/222 (26.6%)		62/237 (26.2%)
Metabolism and nutrition disorders
Albumin, serum-low (hypoalbuminemia)	79/222 (35.6%)		86/237 (36.3%)
Anorexia	77/222 (34.7%)		92/237 (38.8%)
Calcium, serum-high (hypercalcemia)	28/222 (12.6%)		17/237 (7.2%)
Calcium, serum-low (hypocalcemia)	122/222 (55%)		130/237 (54.9%)
Dehydration	19/222 (8.6%)		26/237 (11%)
Glucose, serum-high (hyperglycemia)	140/222 (63.1%)		138/237 (58.2%)
Glucose, serum-low (hypoglycemia)	25/222 (11.3%)		40/237 (16.9%)
Magnesium, serum-low (hypomagnesemia)	30/222 (13.5%)		32/237 (13.5%)
Phosphate, serum-low (hypophosphatemia)	33/222 (14.9%)		24/237 (10.1%)
Potassium, serum-high (hyperkalemia)	25/222 (11.3%)		15/237 (6.3%)
Potassium, serum-low (hypokalemia)	81/222 (36.5%)		92/237 (38.8%)
Sodium, serum-high (hypernatremia)	17/222 (7.7%)		20/237 (8.4%)
Sodium, serum-low (hyponatremia)	66/222 (29.7%)		84/237 (35.4%)
Musculoskeletal and connective tissue disorders
Muscle weakness, not d/t neuropathy - Extrem-lower	15/222 (6.8%)		13/237 (5.5%)
Muscle weakness, not d/t neuropathy - body/general	47/222 (21.2%)		57/237 (24.1%)
Musculoskeletal/Soft Tissue-Other	22/222 (9.9%)		20/237 (8.4%)
Pain - Back	91/222 (41%)		97/237 (40.9%)
Pain - Bone	36/222 (16.2%)		44/237 (18.6%)
Pain - Chest wall	11/222 (5%)		19/237 (8%)
Pain - Extremity-limb	51/222 (23%)		73/237 (30.8%)
Pain - Joint	66/222 (29.7%)		58/237 (24.5%)
Pain - Muscle	51/222 (23%)		62/237 (26.2%)
Pain - Neck	20/222 (9%)		17/237 (7.2%)
Nervous system disorders
Dizziness	71/222 (32%)		86/237 (36.3%)
Memory impairment	5/222 (2.3%)		14/237 (5.9%)
Neurology-Other	15/222 (6.8%)		6/237 (2.5%)
Neuropathy: motor	23/222 (10.4%)		52/237 (21.9%)
Neuropathy: sensory	112/222 (50.5%)		173/237 (73%)
Pain - Head/headache	35/222 (15.8%)		45/237 (19%)
Pain - Neuralgia/peripheral nerve	5/222 (2.3%)		13/237 (5.5%)
Taste alteration (dysgeusia)	56/222 (25.2%)		71/237 (30%)
Tremor	30/222 (13.5%)		25/237 (10.5%)
Psychiatric disorders
Confusion	20/222 (9%)		18/237 (7.6%)
Insomnia	94/222 (42.3%)		99/237 (41.8%)
Mood alteration - anxiety	43/222 (19.4%)		37/237 (15.6%)
Mood alteration - depression	45/222 (20.3%)		41/237 (17.3%)
Renal and urinary disorders
Glomerular filtration rate	12/222 (5.4%)		14/237 (5.9%)
Proteinuria	15/222 (6.8%)		13/237 (5.5%)
Urinary frequency/urgency	16/222 (7.2%)		12/237 (5.1%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	35/222 (15.8%)		28/237 (11.8%)
Cough	77/222 (34.7%)		93/237 (39.2%)
Dyspnea (shortness of breath)	86/222 (38.7%)		86/237 (36.3%)
Hemorrhage, pulmonary/upper respiratory - Nose	19/222 (8.6%)		16/237 (6.8%)
Nasal cavity/paranasal sinus reactions	13/222 (5.9%)		22/237 (9.3%)
Pain - Throat/pharynx/larynx	6/222 (2.7%)		13/237 (5.5%)
Pulmonary/Upper Respiratory-Other	14/222 (6.3%)		14/237 (5.9%)
Voice changes/dysarthria	8/222 (3.6%)		19/237 (8%)
Skin and subcutaneous tissue disorders
Dermatology/Skin-Other	23/222 (10.4%)		16/237 (6.8%)
Dry skin	45/222 (20.3%)		41/237 (17.3%)
Hair loss/Alopecia (scalp or body)	14/222 (6.3%)		20/237 (8.4%)
Pruritus/itching	45/222 (20.3%)		23/237 (9.7%)
Rash/desquamation	57/222 (25.7%)		56/237 (23.6%)
Rash: acne/acneiform	9/222 (4.1%)		17/237 (7.2%)
Sweating (diaphoresis)	27/222 (12.2%)		29/237 (12.2%)
Vascular disorders
Flushing	27/222 (12.2%)		17/237 (7.2%)
Hot flashes/flushes	16/222 (7.2%)		14/237 (5.9%)
Hypertension	37/222 (16.7%)		35/237 (14.8%)
Hypotension	18/222 (8.1%)		27/237 (11.4%)
Thrombosis/thrombus/embolism	21/222 (9.5%)		22/237 (9.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.