S1211 Bortezomib, Dexamethasone, and Lenalidomide With or Without Elotuzumab in Treating Patients With Newly Diagnosed High-Risk Multiple Myeloma

• Sponsor: Southwest Oncology Group (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT01668719
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 142
• Locations: 417
• Arms: 2
• Duration (Months): 139
• Patients Per Site: 0.3
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This partially randomized phase I/II trial studies the side effects and best dose of elotuzumab and to see how well it works when given together with lenalidomide, bortezomib, and dexamethasone in treating patients with newly diagnosed multiple myeloma that is likely to recur (come back), or spread (high-risk). Lenalidomide and bortezomib may stop the growth of multiple myeloma by blocking blood flow to the tumor. Also, bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as lenalidomide and dexamethasone, also work in different ways to kill cancer cells, by stopping them from dividing, or by stopping them from spreading. Giving elotuzumab together with lenalidomide, bortezomib, and dexamethasone may be a better way to block cancer growth.

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; Biological: Elotuzumab; Other: Laboratory Biomarker Analysis; Drug: Lenalidomide	Phase 1/Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To determine the appropriate Phase II dose of elotuzumab to use in combination with lenalidomide, bortezomib, and dexamethasone for patients with multiple myeloma. (Phase I) II. To assess whether incorporation of the novel agent elotuzumab into the treatment algorithm of high-risk multiple myeloma (HRMM) will improve progression-free survival (PFS). (Phase II)
2. To estimate the frequency and severity of toxicities of this treatment strategy in this patient population. (Phase II)

OUTLINE: This is a phase I, dose-escalation study of elotuzumab, followed by a phase II, randomized study.

PHASE I:

INDUCTION: Patients receive bortezomib subcutaneously (SC) or intravenously (IV) on days 1, 4, 8, and 11; lenalidomide orally (PO) once daily (QD) on days 1-14; and dexamethasone PO or IV on days 1, 2, 4, 5, 8, 9, 11, and 12 (and on day 15 of courses 1 and 2 only). Patients also receive elotuzumab IV on days 1, 8, and 15 of courses 1 and 2 and on days 1 and 11 of courses 3-8. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Patients receive bortezomib SC or IV on days 1, 8, and 15; lenalidomide PO QD on days 1-21; dexamethasone PO on days 1, 8, and 15; and elotuzumab IV on days 1 and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

PHASE II: Patients are randomized to 1 of 2 treatment arms.

ARM I:

INDUCTION: Patients receive bortezomib SC or IV on days 1, 4, 8, and 11; lenalidomide PO QD on days 1-14; and dexamethasone PO or IV on days 1, 2, 4, 5, 8, 9, 11, and 12. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity (patients who received a course of chemotherapy prior to registration will begin protocol treatment with course 2 and receive a total of 7 courses of protocol therapy).

MAINTENANCE: Patients receive bortezomib SC or IV on days 1, 8, and 15; lenalidomide PO QD on days 1-21; and dexamethasone PO on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM II:

INDUCTION: Patients receive bortezomib, lenalidomide, and dexamethasone as in Arm I. Patients also receive elotuzumab IV on days 1, 8, and 15 of courses 1 and 2 and on days 1 and 11 of courses 3-8. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Patients receive bortezomib, lenalidomide, and dexamethasone as in Arm I. Patients also receive elotuzumab IV on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for up to 6 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 142 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Phase I/II Study of Optimal Induction Therapy of Bortezomib, Dexamethasone and Lenalidomide With or Without Elotuzumab (NSC-764479) for Newly Diagnosed High Risk Multiple Myeloma (HRMM)
• Study Start Date: Nov 1, 2012
• Actual Primary Completion Date: Feb 1, 2020
• Anticipated Study Completion Date: Jun 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm I (bortezomib, lenalidomide, dexamethasone) INDUCTION: Patients receive bortezomib SC or IV on days 1, 4, 8, and 11; lenalidomide PO QD on days 1-14; and dexamethasone PO or IV on days 1, 2, 4, 5, 8, 9, 11, and 12. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity (patients who received a course of chemotherapy prior to registration will begin protocol treatment with course 2 and receive a total of 7 courses of protocol therapy). MAINTENANCE: Patients receive bortezomib SC or IV on days 1, 8, and 15; lenalidomide PO QD on days 1-21; and dexamethasone PO on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Drug: Bortezomib; Given SC or 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 or IV; Other Names: Aacidexam Adexone Aknichthol Dexa Alba-Dex Alin Alin Depot Alin Oftalmico Amplidermis Anemul mono Auricularum Auxiloson Baycuten Baycuten N Cortidexason Cortisumman Decacort Decadrol Decadron 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 Dexamethasonum Dexamonozon Dexapos Dexinoral Dexone Dinormon Fluorodelta Fortecortin Gammacorten Hexadecadrol Hexadrol Lokalison-F Loverine Methylfluorprednisolone Millicorten Mymethasone Orgadrone Spersadex Visumetazone ; Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Lenalidomide; Given PO; Other Names: CC-5013 CC5013 CDC 501 Revlimid
Experimental: Arm II (bortezomib, lenalidomide, dexamethasone, elotuzumab) INDUCTION: Patients receive bortezomib, lenalidomide, and dexamethasone as in Arm I. Patients also receive elotuzumab IV on days 1, 8, and 15 of courses 1 and 2 and on days 1 and 11 of courses 3-8. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive bortezomib, lenalidomide, and dexamethasone as in Arm I. Patients also receive elotuzumab IV on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Drug: Bortezomib; Given SC or 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 or IV; Other Names: Aacidexam Adexone Aknichthol Dexa Alba-Dex Alin Alin Depot Alin Oftalmico Amplidermis Anemul mono Auricularum Auxiloson Baycuten Baycuten N Cortidexason Cortisumman Decacort Decadrol Decadron 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 Dexamethasonum Dexamonozon Dexapos Dexinoral Dexone Dinormon Fluorodelta Fortecortin Gammacorten Hexadecadrol Hexadrol Lokalison-F Loverine Methylfluorprednisolone Millicorten Mymethasone Orgadrone Spersadex Visumetazone ; Biological: Elotuzumab; Given IV; Other Names: BMS-901608 HuLuc63 PDL-063 PDL063 ; Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Lenalidomide; Given PO; Other Names: CC-5013 CC5013 CDC 501 Revlimid

Outcome Measures

Primary Outcome Measures

1. Phase I: Maximum Tolerated Dose (MTD) of Elotuzumab in Combination With Bortezomib, Lenalidomide and Dexamethasone [time from first participants randomized until at least 6 patients were evaluable for DLTs. DLTs were assessed only during Cycle 1 (21 days)]

   Assess safety of elotuzumab in combination with bortezomib, lenalidomide and dexamethasone and select the optimal dose of elotuzumab for the Phase II portion from 10mg/kg on each cycle, to 5mg/kg on each cycle MTD reflects the highest dose that had a dose-limiting toxicity (DLT) rate of ≤ 1/6 participants. DLTs were defined as treatment regimen related: grade ≥ 3 non-hematologic toxicity; grade 3 nausea or diarrhea despite anti-emetic and anti-diarrheal therapy; grade 3 hyperglycemia if symptomatic or glucose level > 300mg/ml despite insulin and/or oral diabetic therapy; grade 4 neutropenia ≥ 7 days or grade 3/4 neutropenia with fever (≥ 38.5 oC); grade 4 thrombocytopenia ≥ 7 days or associated with hemorrhage; delay of treatment with any agent by > 2 weeks due to drug related toxicity. DLT were graded using the NCI CTCAE version 4.0 Note: i) the second, lower dose level was not tested as the first dose level was deemed safe ii) 6 participants were evaluable at phase I analysis

2. Progression-free Survival [Up to 6 years post registration]

   From date of registration to date of first documentation of progression or death due to any cause. Per the International Uniform Response Criteria for Multiple Myeloma, progression is defined as >=1 of Serum M protein increase >= 25% from lowest response level, with an absolute increase of >= 0.5g/dL; Urine M protein increase >= 25% from lowest response level, with an absolute increase of >= 200 mg/24 hrs; If participant had serum M protein <1 g/dL, urine M protein <200 mg/24 hrs, and an involved serum free light chain level >= 10mg/dL at baseline: >= 25% increase in the difference between involved and uninvolved serum free light chain level with an absolute increase of >= 10 mg/dL; Bone marrow plasma cell % increase =25% from baseline with the absolute plasma cell % >=10%; New bone lesions or soft tissue plasmocytomas, or definite increase in size of existing bone lesions or soft tissue plasmocytomas; Development of hypercalcemia that can be attributed solely to multiple myeloma

Secondary Outcome Measures

1. Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs [Duration of treatment and follow up until death or 6 years post registration, whichever occurs first.]

   Adverse Events (AEs) are reported by CTCAE Version 4.0. Only adverse events that are possibly, probably or definitely related to study drug are reported.

2. Overall Survival [Up to 6 years post registration]

   From date of registration to date of death due to any cause

3. Response (Partial Response [PR] or Better) Rate [Up to 6 years post registration]

   Percentage of participants with PR or better to treatment per the International Uniform Response Criteria for Multiple Myeloma stringent Complete Response- CR criteria + normal serum free light chain (FLC) ratio + absence of clonal cells in bone marrow (BM) by immunohistochemistry or immunofluorescence CR- Negative immunofixation (IFX) on serum & urine M proteins + <5% plasma cells in BM + disappearance of soft tissue plasmocytomas (STP) very good PR- PR criteria + serum & urine M proteins detectable by IFX but not on electrophoresis or >=90% reduction (RED) in serum M protein & urine M protein <100 g/24 hrs PR- >=50% RED in size of STP, if present at baseline & >=50% RED in plasma cells, if >=30% plasma cells in BM at baseline: & RED in serum M protein of >=50% & in urine M protein of >= 90% or to 200 mg/24hr OR if serum M protein <1 g/dL, urine M protein <200 mg/24 hrs, & involved serum FLC level >= 10 mg/dl at baseline: >= 50% RED in (involved-uninvolved) serum FLC levels

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 active multiple myeloma (MM)

• For the Phase II portion only, patients must have high-risk MM based on one or more of the following criteria at the time of initial diagnosis (prior to any chemotherapy):

• Poor-risk genomic signature according to the University of Arkansas 70-gene model (available clinically as myeloma prognostic risk score [MyPRS] score, Signal Genetics, Inc) AND/OR

• Translocation (14;16), and/or translocation (14;20), and/or deletion (17p) by fluorescence in-situ hybridization (FISH) or cytogenetics AND/OR

• Primary plasma cell leukemia (defined by either >= 2,000 plasma cells/mL of peripheral blood, or 20% on a manual differential count) AND/OR

• Serum lactate dehydrogenase (LDH) >= 2 x institutional upper limit of normal (IULN) AND/OR

• 1q21 amplification by FISH analysis AND/OR

• High risk by the SKY92 signature

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

• Patients must have measurable disease within 28 days prior to registration (or prior to initiation of first induction course for patients with prior therapy)

• Patients on the Phase I portion may not have received ANY prior chemotherapy; patients on the Phase II portion may have received one prior cycle of any non-investigational chemotherapy; prior chemotherapy must have been completed within 56 days prior to registration and all toxicities must have resolved to =< grade 1; patients on either portion may have received prior treatment with dexamethasone, providing total number of days of treatment was =< 14 days and total treatment dose was =< 360 mg

• Patients may have received prior radiotherapy for symptomatic localized bone lesions or impending spinal cord compression only; radiotherapy must be completed at least 14 days prior to registration and all toxicities must have resolved to =< grade 1

• Absolute neutrophil count (ANC) >= 1,000 cells/mm^3 without growth factor support

• Platelet count >= 70,000 cells/mm^{3 for patients who have bone marrow plasmacytosis < 50%; or >= 50,000 cells/mm}3 for patients who have bone marrow plasmacytosis of >= 50%

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

• Serum glutamic oxaloacetic transaminase (SGOT)/aspartate aminotransferase (AST) and serum glutamate pyruvate transaminase (SGPT)/alanine aminotransferase (ALT) =< 2.5 x IULN

• Creatinine clearance (CrCL) >= 30 mL/min, measured by a 24-hour urine collection or estimated by the Cockcroft and Gault formula within 14 days prior to registration

• Patients must not have active involvement of the central nervous system (CNS) with MM (by clinical evaluation); patients with documentation of, or clinical signs or symptoms consistent with, CNS involvement of MM must have a lumbar puncture that is negative for CNS involvement of MM; the lumbar puncture must be completed within 14 days prior to registration; patients with no previous history of documented CNS involvement and with no clinical signs or symptoms consistent with CNS involvement are not required to have completed a lumbar puncture prior to registration; note that monitoring of CNS involvement and treatment with intrathecal therapy is recommended during protocol treatment

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

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

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

• No zidovudine or stavudine as part of cART

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

• Patients must have baseline skeletal survey (whole body x-ray) to document lytic lesions, osteopenia or compression fracture

• Patients must have Zubrod performance status =< 2

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

• Patients must not have POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)

• Patients must not have clinically significant illness including uncontrolled, active infection requiring intravenous antibiotics, New York Heart Association (NYHA) class III or class IV heart failure, unstable angina pectoris, myocardial infarction within the past 6 months, uncontrolled >= grade 3 cardiac arrhythmias, uncontrolled hypertension, or uncontrolled diabetes mellitus; patients must have undergone an electrocardiogram (EKG) within 28 days prior to registration

• Uncontrolled diabetes: a glycated hemoglobin (Hg A1C) > 7% within 14 days prior to registration; the same criterion will be used in patients with confirmed diagnosis of diabetes mellitus who have been on a stable dietary or therapeutic regimen for this condition in the last three months

• Uncontrolled blood pressure and hypertension: systolic blood pressure (SBP) > 140 mm Hg or diastolic blood pressure (DBP) > 90 mm Hg within 14 days prior to registration; patients are permitted to be receiving multiple anti-hypertensive medications (unless otherwise indicated in the study); all blood pressure measurements within the 14 days prior to registration and on day 1 of cycle 1 must be SBP =< 140 and DBP =< 90; an exception can be made by a healthcare provider for a patient with a single blood pressure elevation who upon rechecking has a normal blood pressure

• Patients must have history and physical examination 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

• 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 prior to registration; (Note: that pregnancy testing is also required within 24 hours prior to treatment on cycle 1, day 1); furthermore, 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: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) 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)

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

• Patients must be offered participation in banking of specimens for future research; with the patient's consent, specimens (serum and bone marrow biopsy core) must be submitted to the repository; patient consent must be obtained before specimens are submitted

• Patients must be registered to the mandatory Revlimid Risk Evaluation and Mitigation Strategy (REMS)™ program and must be willing and able to comply with the requirements of the Revlimid REMS™ program

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

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alaska Breast Care and Surgery LLC	Anchorage	Alaska	United States	99508
2	Alaska Women's Cancer Care	Anchorage	Alaska	United States	99508
3	Anchorage Oncology Centre	Anchorage	Alaska	United States	99508
4	Katmai Oncology Group	Anchorage	Alaska	United States	99508
5	Providence Alaska Medical Center	Anchorage	Alaska	United States	99508
6	University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
7	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California	United States	91505
8	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010
9	Los Angeles County-USC Medical Center	Los Angeles	California	United States	90033
10	USC / Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033
11	UC Irvine Health/Chao Family Comprehensive Cancer Center	Orange	California	United States	92868
12	Smilow Cancer Hospital-Derby Care Center	Derby	Connecticut	United States	06418
13	Smilow Cancer Hospital Care Center-Fairfield	Fairfield	Connecticut	United States	06824
14	Medical Oncology and Hematology Group PC-Guilford	Guilford	Connecticut	United States	06437
15	Smilow Cancer Hospital Care Center at Saint Francis	Hartford	Connecticut	United States	06105
16	The Hospital of Central Connecticut	New Britain	Connecticut	United States	06050
17	Yale University	New Haven	Connecticut	United States	06520
18	Yale-New Haven Hospital North Haven Medical Center	North Haven	Connecticut	United States	06473
19	Smilow Cancer Hospital-Orange Care Center	Orange	Connecticut	United States	06477
20	Charlotte Hungerford Hospital Center for Cancer Care	Torrington	Connecticut	United States	06790
21	Smilow Cancer Hospital Care Center-Trumbull	Trumbull	Connecticut	United States	06611
22	Smilow Cancer Hospital-Waterbury Care Center	Waterbury	Connecticut	United States	06708
23	Beebe Medical Center	Lewes	Delaware	United States	19958
24	Christiana Gynecologic Oncology LLC	Newark	Delaware	United States	19713
25	Delaware Clinical and Laboratory Physicians PA	Newark	Delaware	United States	19713
26	Helen F Graham Cancer Center	Newark	Delaware	United States	19713
27	Medical Oncology Hematology Consultants PA	Newark	Delaware	United States	19713
28	Regional Hematology and Oncology PA	Newark	Delaware	United States	19713
29	Christiana Care Health System-Christiana Hospital	Newark	Delaware	United States	19718
30	Beebe Health Campus	Rehoboth Beach	Delaware	United States	19971
31	Nanticoke Memorial Hospital	Seaford	Delaware	United States	19973
32	Christiana Care Health System-Wilmington Hospital	Wilmington	Delaware	United States	19801
33	Mayo Clinic in Florida	Jacksonville	Florida	United States	32224-9980
34	Hawaii Oncology Inc-Pali Momi	'Aiea	Hawaii	United States	96701
35	Pali Momi Medical Center	'Aiea	Hawaii	United States	96701
36	Hawaii Cancer Care Inc-POB II	Honolulu	Hawaii	United States	96813
37	Queen's Medical Center	Honolulu	Hawaii	United States	96813
38	Straub Clinic and Hospital	Honolulu	Hawaii	United States	96813
39	University of Hawaii Cancer Center	Honolulu	Hawaii	United States	96813
40	Hawaii Cancer Care Inc-Liliha	Honolulu	Hawaii	United States	96817
41	Hawaii Oncology Inc-Kuakini	Honolulu	Hawaii	United States	96817
42	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii	United States	96826
43	Castle Medical Center	Kailua	Hawaii	United States	96734
44	Wilcox Memorial Hospital and Kauai Medical Clinic	Lihue	Hawaii	United States	96766
45	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho	United States	83706
46	Saint Joseph Medical Center	Bloomington	Illinois	United States	61701
47	Illinois CancerCare-Bloomington	Bloomington	Illinois	United States	61704
48	Illinois CancerCare-Canton	Canton	Illinois	United States	61520
49	Memorial Hospital of Carbondale	Carbondale	Illinois	United States	62902
50	Illinois CancerCare-Carthage	Carthage	Illinois	United States	62321
51	Centralia Oncology Clinic	Centralia	Illinois	United States	62801
52	Cancer Care Center of Decatur	Decatur	Illinois	United States	62526
53	Decatur Memorial Hospital	Decatur	Illinois	United States	62526
54	Crossroads Cancer Center	Effingham	Illinois	United States	62401
55	Illinois CancerCare-Eureka	Eureka	Illinois	United States	61530
56	Illinois CancerCare-Galesburg	Galesburg	Illinois	United States	61401
57	Western Illinois Cancer Treatment Center	Galesburg	Illinois	United States	61401
58	Ingalls Memorial Hospital	Harvey	Illinois	United States	60426
59	Hines Veterans Administration Hospital	Hines	Illinois	United States	60141
60	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois	United States	61443
61	Illinois CancerCare-Macomb	Macomb	Illinois	United States	61455
62	Loyola University Medical Center	Maywood	Illinois	United States	60153
63	Garneau, Stewart C MD (UIA Investigator)	Moline	Illinois	United States	61265
64	Porubcin, Michael MD (UIA Investigator)	Moline	Illinois	United States	61265
65	Spector, David MD (UIA Investigator)	Moline	Illinois	United States	61265
66	Trinity Medical Center	Moline	Illinois	United States	61265
67	Good Samaritan Regional Health Center	Mount Vernon	Illinois	United States	62864
68	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois	United States	61350
69	Radiation Oncology of Northern Illinois	Ottawa	Illinois	United States	61350
70	Illinois CancerCare-Pekin	Pekin	Illinois	United States	61554
71	OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center	Pekin	Illinois	United States	61554
72	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61603
73	Illinois CancerCare-Peoria	Peoria	Illinois	United States	61615
74	OSF Saint Francis Radiation Oncology at Peoria Cancer Center	Peoria	Illinois	United States	61615
75	OSF Saint Francis Medical Center	Peoria	Illinois	United States	61637
76	Illinois CancerCare-Peru	Peru	Illinois	United States	61354
77	Valley Radiation Oncology	Peru	Illinois	United States	61354
78	Illinois CancerCare-Princeton	Princeton	Illinois	United States	61356
79	Central Illinois Hematology Oncology Center	Springfield	Illinois	United States	62702
80	Southern Illinois University School of Medicine	Springfield	Illinois	United States	62702
81	Springfield Clinic	Springfield	Illinois	United States	62702
82	Memorial Medical Center	Springfield	Illinois	United States	62781
83	Cancer Care Specialists of Illinois-Swansea	Swansea	Illinois	United States	62226
84	Reid Health	Richmond	Indiana	United States	47374
85	Mary Greeley Medical Center	Ames	Iowa	United States	50010
86	McFarland Clinic PC-William R Bliss Cancer Center	Ames	Iowa	United States	50010
87	Constantinou, Costas L MD (UIA Investigator)	Bettendorf	Iowa	United States	52722
88	McFarland Clinic PC-Boone	Boone	Iowa	United States	50036
89	McFarland Clinic PC-Trinity Cancer Center	Fort Dodge	Iowa	United States	50501
90	McFarland Clinic PC-Jefferson	Jefferson	Iowa	United States	50129
91	McFarland Clinic PC-Marshalltown	Marshalltown	Iowa	United States	50158
92	Siouxland Regional Cancer Center	Sioux City	Iowa	United States	51101
93	Mercy Medical Center-Sioux City	Sioux City	Iowa	United States	51104
94	Saint Luke's Regional Medical Center	Sioux City	Iowa	United States	51104
95	Newman Regional Health	Emporia	Kansas	United States	66801
96	Saint Catherine Hospital	Garden City	Kansas	United States	67846
97	Saint Rose Ambulatory and Surgery Center	Great Bend	Kansas	United States	67530
98	Hays Medical Center	Hays	Kansas	United States	67601
99	Providence Medical Center	Kansas City	Kansas	United States	66112
100	University of Kansas Cancer Center-West	Kansas City	Kansas	United States	66112
101	University of Kansas Cancer Center	Kansas City	Kansas	United States	66160
102	Lawrence Memorial Hospital	Lawrence	Kansas	United States	66044
103	Kansas Institute of Medicine Cancer and Blood Center	Lenexa	Kansas	United States	66219
104	Minimally Invasive Surgery Hospital	Lenexa	Kansas	United States	66219
105	Olathe Medical Center	Olathe	Kansas	United States	66061
106	Menorah Medical Center	Overland Park	Kansas	United States	66209
107	University of Kansas Cancer Center-Overland Park	Overland Park	Kansas	United States	66210
108	Saint Luke's South Hospital	Overland Park	Kansas	United States	66213
109	Via Christi Hospital-Pittsburg	Pittsburg	Kansas	United States	66762
110	Kansas City NCI Community Oncology Research Program	Prairie Village	Kansas	United States	66208
111	Salina Regional Health Center	Salina	Kansas	United States	67401
112	Cotton O'Neil Cancer Center / Stormont Vail Health	Topeka	Kansas	United States	66606
113	Saint Francis Hospital and Medical Center - Topeka	Topeka	Kansas	United States	66606
114	Wesley Medical Center	Wichita	Kansas	United States	67214
115	Oncology Hematology Care Inc-Crestview	Crestview Hills	Kentucky	United States	41017
116	Hematology/Oncology Clinic LLP	Baton Rouge	Louisiana	United States	70809
117	West Jefferson Medical Center	Marrero	Louisiana	United States	70072
118	Tulane University Health Sciences Center	New Orleans	Louisiana	United States	70112
119	Sinai Hospital of Baltimore	Baltimore	Maryland	United States	21215
120	Walter Reed National Military Medical Center	Bethesda	Maryland	United States	20889-5600
121	Bixby Medical Center	Adrian	Michigan	United States	49221
122	Hickman Cancer Center	Adrian	Michigan	United States	49221
123	Saint Joseph Mercy Hospital	Ann Arbor	Michigan	United States	48106-0995
124	Michigan Cancer Research Consortium NCORP	Ann Arbor	Michigan	United States	48106
125	Bronson Battle Creek	Battle Creek	Michigan	United States	49017
126	Beaumont Hospital-Dearborn	Dearborn	Michigan	United States	48124
127	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan	United States	48201
128	Saint John Hospital and Medical Center	Detroit	Michigan	United States	48236
129	Green Bay Oncology - Escanaba	Escanaba	Michigan	United States	49829
130	Weisberg Cancer Treatment Center	Farmington Hills	Michigan	United States	48334
131	Hurley Medical Center	Flint	Michigan	United States	48502
132	Genesys Hurley Cancer Institute	Flint	Michigan	United States	48503
133	Cancer Research Consortium of West Michigan NCORP	Grand Rapids	Michigan	United States	49503
134	Mercy Health Saint Mary's	Grand Rapids	Michigan	United States	49503
135	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan	United States	49503
136	Green Bay Oncology - Iron Mountain	Iron Mountain	Michigan	United States	49801
137	Allegiance Health	Jackson	Michigan	United States	49201
138	Borgess Medical Center	Kalamazoo	Michigan	United States	49001
139	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
140	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007
141	Sparrow Hospital	Lansing	Michigan	United States	48912
142	Saint Mary Mercy Hospital	Livonia	Michigan	United States	48154
143	Mercy Memorial Hospital	Monroe	Michigan	United States	48162
144	Toledo Clinic Cancer Centers-Monroe	Monroe	Michigan	United States	48162
145	Mercy Health Mercy Campus	Muskegon	Michigan	United States	49444
146	Lakeland Community Hospital	Niles	Michigan	United States	49120
147	Saint Joseph Mercy Oakland	Pontiac	Michigan	United States	48341
148	Lake Huron Medical Center	Port Huron	Michigan	United States	48060
149	Spectrum Health Reed City Hospital	Reed City	Michigan	United States	49677
150	Saint Mary's of Michigan	Saginaw	Michigan	United States	48601
151	Lakeland Hospital	Saint Joseph	Michigan	United States	49085
152	Marie Yeager Cancer Center	Saint Joseph	Michigan	United States	49085
153	Providence Hospital-Southfield Cancer Center	Southfield	Michigan	United States	48075
154	Munson Medical Center	Traverse City	Michigan	United States	49684
155	Saint John Macomb-Oakland Hospital	Warren	Michigan	United States	48093
156	Sanford Clinic North-Bemidgi	Bemidji	Minnesota	United States	56601
157	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
158	Mercy Hospital	Coon Rapids	Minnesota	United States	55433
159	Essentia Health Cancer Center	Duluth	Minnesota	United States	55805
160	Essentia Health Saint Mary's Medical Center	Duluth	Minnesota	United States	55805
161	Miller-Dwan Hospital	Duluth	Minnesota	United States	55805
162	Fairview-Southdale Hospital	Edina	Minnesota	United States	55435
163	Lake Region Healthcare Corporation-Cancer Care	Fergus Falls	Minnesota	United States	56537
164	Unity Hospital	Fridley	Minnesota	United States	55432
165	Hutchinson Area Health Care	Hutchinson	Minnesota	United States	55350
166	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota	United States	55109
167	Saint John's Hospital - Healtheast	Maplewood	Minnesota	United States	55109
168	Abbott-Northwestern Hospital	Minneapolis	Minnesota	United States	55407
169	Hennepin County Medical Center	Minneapolis	Minnesota	United States	55415
170	Health Partners Inc	Minneapolis	Minnesota	United States	55454
171	New Ulm Medical Center	New Ulm	Minnesota	United States	56073
172	North Memorial Medical Health Center	Robbinsdale	Minnesota	United States	55422
173	Mayo Clinic	Rochester	Minnesota	United States	55905
174	Metro Minnesota Community Oncology Research Consortium	Saint Louis Park	Minnesota	United States	55416
175	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota	United States	55416
176	Regions Hospital	Saint Paul	Minnesota	United States	55101
177	United Hospital	Saint Paul	Minnesota	United States	55102
178	Saint Francis Regional Medical Center	Shakopee	Minnesota	United States	55379
179	Lakeview Hospital	Stillwater	Minnesota	United States	55082
180	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
181	Rice Memorial Hospital	Willmar	Minnesota	United States	56201
182	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota	United States	55125
183	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
184	Central Care Cancer Center-Carrie J Babb Cancer Center	Bolivar	Missouri	United States	65613
185	Parkland Health Center-Bonne Terre	Bonne Terre	Missouri	United States	63628
186	CoxHealth Cancer Center	Branson	Missouri	United States	65616
187	Saint Francis Medical Center	Cape Girardeau	Missouri	United States	63703
188	Southeast Cancer Center	Cape Girardeau	Missouri	United States	63703
189	Centerpoint Medical Center LLC	Independence	Missouri	United States	64057
190	Capital Region Medical Center-Goldschmidt Cancer Center	Jefferson City	Missouri	United States	65109
191	Truman Medical Center	Kansas City	Missouri	United States	64108
192	Saint Luke's Hospital of Kansas City	Kansas City	Missouri	United States	64111
193	North Kansas City Hospital	Kansas City	Missouri	United States	64116
194	Heartland Hematology and Oncology Associates Incorporated	Kansas City	Missouri	United States	64118
195	The University of Kansas Cancer Center-South	Kansas City	Missouri	United States	64131
196	Research Medical Center	Kansas City	Missouri	United States	64132
197	The University of Kansas Cancer Center-North	Kansas City	Missouri	United States	64154
198	The University of Kansas Cancer Center-Lee's Summit	Lee's Summit	Missouri	United States	64064
199	Saint Luke's East - Lee's Summit	Lee's Summit	Missouri	United States	64086
200	Liberty Radiation Oncology Center	Liberty	Missouri	United States	64068
201	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri	United States	65401
202	Saint John's Clinic-Rolla-Cancer and Hematology	Rolla	Missouri	United States	65401
203	Heartland Regional Medical Center	Saint Joseph	Missouri	United States	64506
204	Saint Joseph Oncology Inc	Saint Joseph	Missouri	United States	64507
205	Saint Louis Cancer and Breast Institute-South City	Saint Louis	Missouri	United States	63109
206	Missouri Baptist Medical Center	Saint Louis	Missouri	United States	63131
207	Mercy Hospital Saint Louis	Saint Louis	Missouri	United States	63141
208	Sainte Genevieve County Memorial Hospital	Sainte Genevieve	Missouri	United States	63670
209	Cancer Research for the Ozarks NCORP	Springfield	Missouri	United States	65804
210	Mercy Hospital Springfield	Springfield	Missouri	United States	65804
211	CoxHealth South Hospital	Springfield	Missouri	United States	65807
212	Missouri Baptist Sullivan Hospital	Sullivan	Missouri	United States	63080
213	Missouri Baptist Outpatient Center-Sunset Hills	Sunset Hills	Missouri	United States	63127
214	Nebraska Hematology and Oncology	Lincoln	Nebraska	United States	68506
215	Nebraska Cancer Research Center	Lincoln	Nebraska	United States	68510
216	Southeast Nebraska Cancer Center	Lincoln	Nebraska	United States	68510
217	Faith Regional Medical Offices West	Norfolk	Nebraska	United States	68701
218	Great Plains Regional Medical Center	North Platte	Nebraska	United States	69103
219	Missouri Valley Cancer Consortium	Omaha	Nebraska	United States	68106
220	Alegent Health Immanuel Medical Center	Omaha	Nebraska	United States	68122
221	Alegent Health Bergan Mercy Medical Center	Omaha	Nebraska	United States	68124
222	Oncology Hematology West	Omaha	Nebraska	United States	68124
223	Alegent Health Lakeside Hospital	Omaha	Nebraska	United States	68130
224	Oncology Hematology West PC	Omaha	Nebraska	United States	68130
225	Urology Cancer Center PC	Omaha	Nebraska	United States	68130
226	Creighton University Medical Center	Omaha	Nebraska	United States	68131
227	Regional West Medical Center	Scottsbluff	Nebraska	United States	69361
228	Cancer and Blood Specialists-Henderson	Henderson	Nevada	United States	89052
229	Comprehensive Cancer Centers of Nevada - Henderson	Henderson	Nevada	United States	89052
230	Las Vegas Cancer Center-Henderson	Henderson	Nevada	United States	89052
231	21st Century Oncology - Henderson	Henderson	Nevada	United States	89074
232	Comprehensive Cancer Centers of Nevada-Southeast Henderson	Henderson	Nevada	United States	89074
233	University Medical Center of Southern Nevada	Las Vegas	Nevada	United States	89102
234	Cancer and Blood Specialists-Shadow	Las Vegas	Nevada	United States	89106
235	Nevada Cancer Research Foundation CCOP	Las Vegas	Nevada	United States	89106
236	Radiation Oncology Centers of Nevada Central	Las Vegas	Nevada	United States	89106
237	21st Century Oncology	Las Vegas	Nevada	United States	89109
238	HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway	Las Vegas	Nevada	United States	89109
239	HealthCare Partners Medical Group Oncology/Hematology-San Martin	Las Vegas	Nevada	United States	89113
240	Radiation Oncology Centers of Nevada Southeast	Las Vegas	Nevada	United States	89119
241	Cancer Therapy and Integrative Medicine	Las Vegas	Nevada	United States	89121
242	Cancer and Blood Specialists-Tenaya	Las Vegas	Nevada	United States	89128
243	Comprehensive Cancer Centers of Nevada - Northwest	Las Vegas	Nevada	United States	89128
244	HealthCare Partners Medical Group Oncology/Hematology-Tenaya	Las Vegas	Nevada	United States	89128
245	Comprehensive Cancer Centers of Nevada-Summerlin	Las Vegas	Nevada	United States	89144
246	Las Vegas Cancer Center-Medical Center	Las Vegas	Nevada	United States	89148-2405
247	21st Century Oncology - Fort Apache	Las Vegas	Nevada	United States	89148
248	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada	United States	89148
249	Nevada Cancer Specialists-Fort Apache	Las Vegas	Nevada	United States	89148
250	HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills	Las Vegas	Nevada	United States	89149
251	Comprehensive Cancer Centers of Nevada - Central Valley	Las Vegas	Nevada	United States	89169
252	21st Century Oncology - Vegas Tenaya	Las Vegas	Nevada	United States	89182
253	Orange Regional Medical Center	Middletown	New York	United States	10940
254	University of Rochester	Rochester	New York	United States	14642
255	Staten Island University Hospital	Staten Island	New York	United States	10305
256	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina	United States	28203
257	Southeastern Medical Oncology Center-Clinton	Clinton	North Carolina	United States	28328
258	Carolinas HealthCare System NorthEast	Concord	North Carolina	United States	28025
259	Southeastern Medical Oncology Center-Goldsboro	Goldsboro	North Carolina	United States	27534
260	Wayne Memorial Hospital	Goldsboro	North Carolina	United States	27534
261	Southeastern Medical Oncology Center-Jacksonville	Jacksonville	North Carolina	United States	28546
262	Kinston Medical Specialists PA	Kinston	North Carolina	United States	28501
263	Carolinas HealthCare System Union	Monroe	North Carolina	United States	28112
264	FirstHealth of the Carolinas-Moore Regional Hosiptal	Pinehurst	North Carolina	United States	28374
265	Iredell Memorial Hospital	Statesville	North Carolina	United States	28677
266	Southeastern Medical Oncology Center-Wilson	Wilson	North Carolina	United States	27893
267	Sanford Bismarck Medical Center	Bismarck	North Dakota	United States	58501
268	Roger Maris Cancer Center	Fargo	North Dakota	United States	58122
269	Sanford Clinic North-Fargo	Fargo	North Dakota	United States	58122
270	Sanford Medical Center-Fargo	Fargo	North Dakota	United States	58122
271	Cleveland Clinic Cancer Center Beachwood	Beachwood	Ohio	United States	44122
272	Strecker Cancer Center-Belpre	Belpre	Ohio	United States	45714
273	Toledo Clinic Cancer Centers-Bowling Green	Bowling Green	Ohio	United States	43402
274	Miami Valley Hospital South	Centerville	Ohio	United States	45459
275	Geaugra Hospital	Chardon	Ohio	United States	44024
276	Adena Regional Medical Center	Chillicothe	Ohio	United States	45601
277	Oncology Hematology Care Inc-Eden Park	Cincinnati	Ohio	United States	45202
278	Oncology Hematology Care Inc-Mercy West	Cincinnati	Ohio	United States	45211
279	Oncology Hematology Care Inc - Anderson	Cincinnati	Ohio	United States	45230
280	Oncology Hematology Care Inc-Kenwood	Cincinnati	Ohio	United States	45236
281	Oncology Hematology Care Inc-Blue Ash	Cincinnati	Ohio	United States	45242
282	Case Western Reserve University	Cleveland	Ohio	United States	44106
283	Cleveland Clinic Cancer Center/Fairview Hospital	Cleveland	Ohio	United States	44111
284	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
285	Mount Carmel East Hospital	Columbus	Ohio	United States	43213
286	Columbus Oncology and Hematology Associates Inc	Columbus	Ohio	United States	43214
287	Riverside Methodist Hospital	Columbus	Ohio	United States	43214
288	Columbus NCI Community Oncology Research Program	Columbus	Ohio	United States	43215
289	Grant Medical Center	Columbus	Ohio	United States	43215
290	The Mark H Zangmeister Center	Columbus	Ohio	United States	43219
291	Mount Carmel Health Center West	Columbus	Ohio	United States	43222
292	Doctors Hospital	Columbus	Ohio	United States	43228
293	Good Samaritan Hospital - Dayton	Dayton	Ohio	United States	45406
294	Miami Valley Hospital	Dayton	Ohio	United States	45409
295	Samaritan North Health Center	Dayton	Ohio	United States	45415
296	Delaware Health Center-Grady Cancer Center	Delaware	Ohio	United States	43015
297	Delaware Radiation Oncology	Delaware	Ohio	United States	43015
298	Grady Memorial Hospital	Delaware	Ohio	United States	43015
299	Mercy Cancer Center-Elyria	Elyria	Ohio	United States	44035
300	Oncology Hematology Care Inc-Healthplex	Fairfield	Ohio	United States	45014
301	Blanchard Valley Hospital	Findlay	Ohio	United States	45840
302	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio	United States	45005-1066
303	Wayne Hospital	Greenville	Ohio	United States	45331
304	Cleveland Clinic Cancer Center Independence	Independence	Ohio	United States	44131
305	Kettering Medical Center	Kettering	Ohio	United States	45429
306	Fairfield Medical Center	Lancaster	Ohio	United States	43130
307	Lancaster Radiation Oncology	Lancaster	Ohio	United States	43130
308	Lima Memorial Hospital	Lima	Ohio	United States	45804
309	OhioHealth Mansfield Hospital	Mansfield	Ohio	United States	44903
310	Cleveland Clinic Cancer Center Mansfield	Mansfield	Ohio	United States	44906
311	Marietta Memorial Hospital	Marietta	Ohio	United States	45750
312	OneHealth Marion General Hospital	Marion	Ohio	United States	43302
313	Toledo Clinic Cancer Centers-Maumee	Maumee	Ohio	United States	43537
314	Toledo Radiation Oncology at Northwest Ohio Onocolgy Center	Maumee	Ohio	United States	43537
315	Hillcrest Hospital Cancer Center	Mayfield Heights	Ohio	United States	44124
316	Ireland Cancer Center Landerbrook Health Center	Mayfield Heights	Ohio	United States	44124
317	Lake University Ireland Cancer Center	Mentor	Ohio	United States	44060
318	Knox Community Hospital	Mount Vernon	Ohio	United States	43050
319	Licking Memorial Hospital	Newark	Ohio	United States	43055
320	Newark Radiation Oncology	Newark	Ohio	United States	43055
321	Saint Charles Hospital	Oregon	Ohio	United States	43616
322	Toledo Clinic Cancer Centers-Oregon	Oregon	Ohio	United States	43616
323	University Hospitals Parma Medical Center	Parma	Ohio	United States	44129
324	Southern Ohio Medical Center	Portsmouth	Ohio	United States	45662
325	Ireland Cancer Center at Firelands Regional Medical Center	Sandusky	Ohio	United States	44870
326	North Coast Cancer Care	Sandusky	Ohio	United States	44870
327	Springfield Regional Cancer Center	Springfield	Ohio	United States	45504
328	Springfield Regional Medical Center	Springfield	Ohio	United States	45505
329	Cleveland Clinic Cancer Center Strongsville	Strongsville	Ohio	United States	44136
330	Flower Hospital	Sylvania	Ohio	United States	43560
331	Mercy Hospital of Tiffin	Tiffin	Ohio	United States	44883
332	The Toledo Hospital/Toledo Children's Hospital	Toledo	Ohio	United States	43606
333	Saint Vincent Mercy Medical Center	Toledo	Ohio	United States	43608
334	University of Toledo	Toledo	Ohio	United States	43614
335	Toledo Community Hospital Oncology Program CCOP	Toledo	Ohio	United States	43617
336	Mercy Saint Anne Hospital	Toledo	Ohio	United States	43623
337	Toledo Clinic Cancer Centers-Toledo	Toledo	Ohio	United States	43623
338	Upper Valley Medical Center	Troy	Ohio	United States	45373
339	South Pointe Hospital	Warrensville Heights	Ohio	United States	44122
340	Fulton County Health Center	Wauseon	Ohio	United States	43567
341	Saint Ann's Hospital	Westerville	Ohio	United States	43081
342	UH-Seidman Cancer Center at Saint John Medical Center	Westlake	Ohio	United States	44145
343	Cleveland Clinic Wooster Family Health and Surgery Center	Wooster	Ohio	United States	44691
344	Genesis Healthcare System Cancer Care Center	Zanesville	Ohio	United States	43701
345	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
346	Clackamas Radiation Oncology Center	Clackamas	Oregon	United States	97015
347	Providence Oncology and Hematology Care Southeast	Clackamas	Oregon	United States	97015
348	Legacy Mount Hood Medical Center	Gresham	Oregon	United States	97030
349	Providence Milwaukie Hospital	Milwaukie	Oregon	United States	97222
350	Providence Newberg Medical Center	Newberg	Oregon	United States	97132
351	Providence Willamette Falls Medical Center	Oregon City	Oregon	United States	97045
352	Legacy Good Samaritan Hospital and Medical Center	Portland	Oregon	United States	97210
353	Providence Portland Medical Center	Portland	Oregon	United States	97213
354	Providence Saint Vincent Medical Center	Portland	Oregon	United States	97225
355	Legacy Meridian Park Hospital	Tualatin	Oregon	United States	97062
356	Geisinger Medical Center	Danville	Pennsylvania	United States	17822
357	Geisinger Medical Center-Cancer Center Hazleton	Hazleton	Pennsylvania	United States	18201
358	Geisinger Medical Oncology-Lewisburg	Lewisburg	Pennsylvania	United States	17837
359	Lewistown Hospital	Lewistown	Pennsylvania	United States	17044
360	Geisinger Medical Oncology-Pottsville	Pottsville	Pennsylvania	United States	17901
361	Geisinger Medical Group	State College	Pennsylvania	United States	16801
362	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania	United States	18711
363	Medical University of South Carolina	Charleston	South Carolina	United States	29425
364	McLeod Regional Medical Center	Florence	South Carolina	United States	29506
365	Self Regional Healthcare	Greenwood	South Carolina	United States	29646
366	Rapid City Regional Hospital	Rapid City	South Dakota	United States	57701
367	Sanford Cancer Center-Oncology Clinic	Sioux Falls	South Dakota	United States	57104
368	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota	United States	57117-5134
369	M D Anderson Cancer Center	Houston	Texas	United States	77030
370	Fredericksburg Oncology Inc	Fredericksburg	Virginia	United States	22401
371	Memorial Hospital Of Martinsville	Martinsville	Virginia	United States	24115
372	PeaceHealth Saint John Medical Center	Longview	Washington	United States	98632
373	PeaceHealth Southwest Medical Center	Vancouver	Washington	United States	98664
374	Compass Oncology Vancouver	Vancouver	Washington	United States	98684
375	Legacy Salmon Creek Hospital	Vancouver	Washington	United States	98686
376	Aurora Cancer Care-Southern Lakes VLCC	Burlington	Wisconsin	United States	53105
377	Marshfield Clinic-Chippewa Center	Chippewa Falls	Wisconsin	United States	54729
378	Marshfield Clinic Cancer Center at Sacred Heart	Eau Claire	Wisconsin	United States	54701
379	Aurora Health Center-Fond du Lac	Fond Du Lac	Wisconsin	United States	54937
380	Aurora Health Care Germantown Health Center	Germantown	Wisconsin	United States	53022
381	Aurora Cancer Care-Grafton	Grafton	Wisconsin	United States	53024
382	Green Bay Oncology at Saint Vincent Hospital	Green Bay	Wisconsin	United States	54301-3526
383	Saint Vincent Hospital Cancer Center Green Bay	Green Bay	Wisconsin	United States	54301
384	Green Bay Oncology Limited at Saint Mary's Hospital	Green Bay	Wisconsin	United States	54303
385	Saint Vincent Hospital Cancer Center at Saint Mary's	Green Bay	Wisconsin	United States	54303
386	Aurora BayCare Medical Center	Green Bay	Wisconsin	United States	54311
387	Aurora Cancer Care-Kenosha South	Kenosha	Wisconsin	United States	53142
388	Gundersen Lutheran Medical Center	La Crosse	Wisconsin	United States	54601
389	University of Wisconsin Hospital and Clinics	Madison	Wisconsin	United States	53792
390	Holy Family Memorial Hospital	Manitowoc	Wisconsin	United States	54221
391	Bay Area Medical Center	Marinette	Wisconsin	United States	54143
392	Vince Lombardi Cancer Clinic-Marinette	Marinette	Wisconsin	United States	54143
393	Marshfield Clinic	Marshfield	Wisconsin	United States	54449
394	Aurora Cancer Care-Milwaukee	Milwaukee	Wisconsin	United States	53209
395	Aurora Saint Luke's Medical Center	Milwaukee	Wisconsin	United States	53215
396	Aurora Sinai Medical Center	Milwaukee	Wisconsin	United States	53233
397	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin	United States	54548
398	Cancer Center of Western Wisconsin	New Richmond	Wisconsin	United States	54017
399	Green Bay Oncology - Oconto Falls	Oconto Falls	Wisconsin	United States	54154
400	Vince Lombardi Cancer Clinic - Oshkosh	Oshkosh	Wisconsin	United States	54904
401	Aurora Cancer Care-Racine	Racine	Wisconsin	United States	53406
402	Marshfield Clinic at James Beck Cancer Center	Rhinelander	Wisconsin	United States	54501
403	Lakeview Medical Center-Marshfield Clinic	Rice Lake	Wisconsin	United States	54868
404	Marshfield Clinic-Rice Lake Center	Rice Lake	Wisconsin	United States	54868
405	HSHS Saint Nicholas Hospital	Sheboygan	Wisconsin	United States	53081
406	Vince Lombardi Cancer Clinic-Sheboygan	Sheboygan	Wisconsin	United States	53081
407	Marshfield Clinic Cancer Care at Saint Michael's Hospital	Stevens Point	Wisconsin	United States	54481
408	Green Bay Oncology - Sturgeon Bay	Sturgeon Bay	Wisconsin	United States	54235
409	Aurora Medical Center in Summit	Summit	Wisconsin	United States	53066
410	Vince Lombardi Cancer Clinic-Two Rivers	Two Rivers	Wisconsin	United States	54241
411	Aurora Cancer Care-Waukesha	Waukesha	Wisconsin	United States	53188
412	Marshfield Clinic-Wausau Center	Wausau	Wisconsin	United States	54401
413	Aurora Cancer Care-Milwaukee West	Wauwatosa	Wisconsin	United States	53226
414	Aurora West Allis Medical Center	West Allis	Wisconsin	United States	53227
415	Diagnostic and Treatment Center	Weston	Wisconsin	United States	54476
416	Marshfield Clinic - Weston Center	Weston	Wisconsin	United States	54476
417	Marshfield Clinic - Wisconsin Rapids Center	Wisconsin Rapids	Wisconsin	United States	54494

Sponsors and Collaborators

• Southwest Oncology Group
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Saad Usmani, Southwest Oncology Group

Study Documents (Full-Text)

• Study Protocol, Statistical Analysis Plan, and Informed Consent Form - May 21, 2019

More Information

Publications

None provided.

• Responsible Party: Southwest Oncology Group
• ClinicalTrials.gov Identifier: NCT01668719
• Other Study ID Numbers: S1211; NCI-2012-01998; PS1211_A12PAMDREVW01; CDR0000738512; S1211; S1211; U10CA180888; U10CA032102
• First Posted: Aug 20, 2012
• Last Update Posted: May 24, 2022
• Last Verified: May 1, 2022

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

Study Results

Participant Flow

Pre-assignment Detail	8 participants were enrolled to the Phase 1 Level 1 dose arm. 2 were ineligible, so 6 participants were assessed for DLT. In Phase II, 68 participants were enrolled on RVD and 66 to RVD/Elo arm. of these, 16 and 18 respectively were ineligible. Thus, 52 participants on RVD and 48 participants on RVD/Elo arm were eligible and evaluable for analyses.

Arm/Group Title	Phase I Dose Level 1 (Elotuzumab, 10mg, and Bortezomib, Lenalidomide and Dexamethasone)	Arm I (Bortezomib, Lenalidomide, Dexamethasone)	Arm II (Bortezomib, Lenalidomide, Dexamethasone, Elotuzumab)
Arm/Group Description	INDUCTION: Participants receive bortezomib subcutaneously (SC) or intravenously (IV) on days 1, 4, 8, and 11; lenalidomide orally (PO) once daily (QD) on days 1-14; and dexamethasone PO or IV on days 1, 2, 4, 5, 8, 9, 11, and 12 (and on day 15 of courses 1 and 2 only). Participants also receive elotuzumab IV on days 1, 8, and 15 of courses 1 and 2 and on days 1 and 11 of courses 3-8. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Participants receive bortezomib SC or IV on days 1, 8, and 15; lenalidomide PO QD on days 1-21; dexamethasone PO on days 1, 8, and 15; and elotuzumab IV on days 1 and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.	INDUCTION: Participants receive bortezomib SC or IV on days 1, 4, 8, and 11; lenalidomide PO QD on days 1-14; and dexamethasone PO or IV on days 1, 2, 4, 5, 8, 9, 11, and 12. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity (participants who received a course of chemotherapy prior to registration will begin protocol treatment with course 2 and receive a total of 7 courses of protocol therapy). MAINTENANCE: Participants receive bortezomib SC or IV on days 1, 8, and 15; lenalidomide PO QD on days 1-21; and dexamethasone PO on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Bortezomib: Given SC or IV Dexamethasone: Given PO or IV Laboratory Biomarker Analysis: Correlative studies Lenalidomide: Given PO	INDUCTION: Participants receive bortezomib, lenalidomide, and dexamethasone as in Arm I. Participants also receive elotuzumab IV on days 1, 8, and 15 of courses 1 and 2 and on days 1 and 11 of courses 3-8. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Participants receive bortezomib, lenalidomide, and dexamethasone as in Arm I. Participants also receive elotuzumab IV on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Bortezomib: Given SC or IV Dexamethasone: Given PO or IV Elotuzumab: Given IV Laboratory Biomarker Analysis: Correlative studies Lenalidomide: Given PO
Period Title: Phase I
STARTED	6	0	0
COMPLETED	0	0	0
NOT COMPLETED	6	0	0
Period Title: Phase I
STARTED	0	52	48
COMPLETED	0	0	0
NOT COMPLETED	0	52	48

Baseline Characteristics

Arm/Group Title	Phase I Dose Level 1 (Elotuzumab, 10mg, and Bortezomib, Lenalidomide and Dexamethasone)	Arm I (Bortezomib, Lenalidomide, Dexamethasone)	Arm II (Bortezomib, Lenalidomide, Dexamethasone, Elotuzumab)	Total
Arm/Group Description	INDUCTION: Participants receive bortezomib subcutaneously (SC) or intravenously (IV) on days 1, 4, 8, and 11; lenalidomide orally (PO) once daily (QD) on days 1-14; and dexamethasone PO or IV on days 1, 2, 4, 5, 8, 9, 11, and 12 (and on day 15 of courses 1 and 2 only). Participants also receive elotuzumab IV on days 1, 8, and 15 of courses 1 and 2 and on days 1 and 11 of courses 3-8. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Participants receive bortezomib SC or IV on days 1, 8, and 15; lenalidomide PO QD on days 1-21; dexamethasone PO on days 1, 8, and 15; and elotuzumab IV on days 1 and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.	INDUCTION: Participants receive bortezomib SC or IV on days 1, 4, 8, and 11; lenalidomide PO QD on days 1-14; and dexamethasone PO or IV on days 1, 2, 4, 5, 8, 9, 11, and 12. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity (participants who received a course of chemotherapy prior to registration will begin protocol treatment with course 2 and receive a total of 7 courses of protocol therapy). MAINTENANCE: Participants receive bortezomib SC or IV on days 1, 8, and 15; lenalidomide PO QD on days 1-21; and dexamethasone PO on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Bortezomib: Given SC or IV Dexamethasone: Given PO or IV Laboratory Biomarker Analysis: Correlative studies Lenalidomide: Given PO	INDUCTION: Participants receive bortezomib, lenalidomide, and dexamethasone as in Arm I. Participants also receive elotuzumab IV on days 1, 8, and 15 of courses 1 and 2 and on days 1 and 11 of courses 3-8. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE:Participants receive bortezomib, lenalidomide, and dexamethasone as in Arm I. Participants also receive elotuzumab IV on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Bortezomib: Given SC or IV Dexamethasone: Given PO or IV Elotuzumab: Given IV Laboratory Biomarker Analysis: Correlative studies Lenalidomide: Given PO	Total of all reporting groups
Overall Participants	6	52	48	106
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	67.6	65.6	62.3	64.2
Sex: Female, Male (Count of Participants)
Female	3 50%	21 40.4%	19 39.6%	43 40.6%
Male	3 50%	31 59.6%	29 60.4%	63 59.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 16.7%	0 0%	2 4.2%	3 2.8%
Not Hispanic or Latino	5 83.3%	48 92.3%	45 93.8%	98 92.5%
Unknown or Not Reported	0 0%	4 7.7%	1 2.1%	5 4.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	1 16.7%	8 15.4%	6 12.5%	15 14.2%
White	3 50%	44 84.6%	41 85.4%	88 83%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	2 33.3%	0 0%	1 2.1%	3 2.8%
PCL and/or high LDH (Count of Participants)
Yes	1 16.7%	9 17.3%	6 12.5%	16 15.1%
No	5 83.3%	43 82.7%	42 87.5%	90 84.9%

Outcome Measures

1. Primary Outcome

Title	Phase I: Maximum Tolerated Dose (MTD) of Elotuzumab in Combination With Bortezomib, Lenalidomide and Dexamethasone
Description	Assess safety of elotuzumab in combination with bortezomib, lenalidomide and dexamethasone and select the optimal dose of elotuzumab for the Phase II portion from 10mg/kg on each cycle, to 5mg/kg on each cycle MTD reflects the highest dose that had a dose-limiting toxicity (DLT) rate of ≤ 1/6 participants. DLTs were defined as treatment regimen related: grade ≥ 3 non-hematologic toxicity; grade 3 nausea or diarrhea despite anti-emetic and anti-diarrheal therapy; grade 3 hyperglycemia if symptomatic or glucose level > 300mg/ml despite insulin and/or oral diabetic therapy; grade 4 neutropenia ≥ 7 days or grade 3/4 neutropenia with fever (≥ 38.5 oC); grade 4 thrombocytopenia ≥ 7 days or associated with hemorrhage; delay of treatment with any agent by > 2 weeks due to drug related toxicity. DLT were graded using the NCI CTCAE version 4.0 Note: i) the second, lower dose level was not tested as the first dose level was deemed safe ii) 6 participants were evaluable at phase I analysis
Time Frame	time from first participants randomized until at least 6 patients were evaluable for DLTs. DLTs were assessed only during Cycle 1 (21 days)

Outcome Measure Data

Analysis Population Description

At the time of the phase I analysis, six participants were evaluable for DLTs (i.e. were eligible and received at least one dose of study drug).

Arm/Group Title	Phase I Dose Level 1 (Elotuzumab, 10mg, and Bortezomib, Lenalidomide and Dexamethasone)
Arm/Group Description	INDUCTION: Participants receive bortezomib subcutaneously (SC) or intravenously (IV) on days 1, 4, 8, and 11; lenalidomide orally (PO) once daily (QD) on days 1-14; and dexamethasone PO or IV on days 1, 2, 4, 5, 8, 9, 11, and 12 (and on day 15 of courses 1 and 2 only). Participants also receive elotuzumab IV on days 1, 8, and 15 of courses 1 and 2 and on days 1 and 11 of courses 3-8. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Participants receive bortezomib SC or IV on days 1, 8, and 15; lenalidomide PO QD on days 1-21; dexamethasone PO on days 1, 8, and 15; and elotuzumab IV on days 1 and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	6
Number [mg/kg (Phase II dosing for elotuzumab)]	10

2. Primary Outcome

Title	Progression-free Survival
Description	From date of registration to date of first documentation of progression or death due to any cause. Per the International Uniform Response Criteria for Multiple Myeloma, progression is defined as >=1 of Serum M protein increase >= 25% from lowest response level, with an absolute increase of >= 0.5g/dL; Urine M protein increase >= 25% from lowest response level, with an absolute increase of >= 200 mg/24 hrs; If participant had serum M protein <1 g/dL, urine M protein <200 mg/24 hrs, and an involved serum free light chain level >= 10mg/dL at baseline: >= 25% increase in the difference between involved and uninvolved serum free light chain level with an absolute increase of >= 10 mg/dL; Bone marrow plasma cell % increase =25% from baseline with the absolute plasma cell % >=10%; New bone lesions or soft tissue plasmocytomas, or definite increase in size of existing bone lesions or soft tissue plasmocytomas; Development of hypercalcemia that can be attributed solely to multiple myeloma
Time Frame	Up to 6 years post registration

Outcome Measure Data

Analysis Population Description

Eligible and analyzable participants

Arm/Group Title	Arm I (Bortezomib, Lenalidomide, Dexamethasone)	Arm II (Bortezomib, Lenalidomide, Dexamethasone, Elotuzumab)
Arm/Group Description	INDUCTION: Participants receive bortezomib SC or IV on days 1, 4, 8, and 11; lenalidomide PO QD on days 1-14; and dexamethasone PO or IV on days 1, 2, 4, 5, 8, 9, 11, and 12. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity (participants who received a course of chemotherapy prior to registration will begin protocol treatment with course 2 and receive a total of 7 courses of protocol therapy). MAINTENANCE: Participants receive bortezomib SC or IV on days 1, 8, and 15; lenalidomide PO QD on days 1-21; and dexamethasone PO on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Bortezomib: Given SC or IV Dexamethasone: Given PO or IV Laboratory Biomarker Analysis: Correlative studies Lenalidomide: Given PO	INDUCTION: Participants receive bortezomib, lenalidomide, and dexamethasone as in Arm I. Participants also receive elotuzumab IV on days 1, 8, and 15 of courses 1 and 2 and on days 1 and 11 of courses 3-8. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE:Participants receive bortezomib, lenalidomide, and dexamethasone as in Arm I. Participants also receive elotuzumab IV on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Bortezomib: Given SC or IV Dexamethasone: Given PO or IV Elotuzumab: Given IV Laboratory Biomarker Analysis: Correlative studies Lenalidomide: Given PO
Measure Participants	52	48
Median (95% Confidence Interval) [months]	33.6	31.5

3. Secondary Outcome

Title	Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs
Description	Adverse Events (AEs) are reported by CTCAE Version 4.0. Only adverse events that are possibly, probably or definitely related to study drug are reported.
Time Frame	Duration of treatment and follow up until death or 6 years post registration, whichever occurs first.

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose of protocol treatment.

Arm/Group Title	Arm I (Bortezomib, Lenalidomide, Dexamethasone)	Arm II (Bortezomib, Lenalidomide, Dexamethasone, Elotuzumab)
Arm/Group Description	INDUCTION: Participants receive bortezomib SC or IV on days 1, 4, 8, and 11; lenalidomide PO QD on days 1-14; and dexamethasone PO or IV on days 1, 2, 4, 5, 8, 9, 11, and 12. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity (participants who received a course of chemotherapy prior to registration will begin protocol treatment with course 2 and receive a total of 7 courses of protocol therapy). MAINTENANCE: Participants receive bortezomib SC or IV on days 1, 8, and 15; lenalidomide PO QD on days 1-21; and dexamethasone PO on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Bortezomib: Given SC or IV Dexamethasone: Given PO or IV Lenalidomide: Given PO	INDUCTION: Participants receive bortezomib, lenalidomide, and dexamethasone as in Arm I. Participants also receive elotuzumab IV on days 1, 8, and 15 of courses 1 and 2 and on days 1 and 11 of courses 3-8. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Participants receive bortezomib, lenalidomide, and dexamethasone as in Arm I. Participants also receive elotuzumab IV on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Bortezomib: Given SC or IV Dexamethasone: Given PO or IV Elotuzumab: Given IV Lenalidomide: Given PO
Measure Participants	52	48
Abdominal pain	1 16.7%	0 0%
Acute kidney injury	1 16.7%	0 0%
Agitation	0 0%	1 1.9%
Alanine aminotransferase increased	0 0%	2 3.8%
Alkaline phosphatase increased	0 0%	1 1.9%
Allergic reaction	0 0%	1 1.9%
Anemia	8 133.3%	6 11.5%
Aspartate aminotransferase increased	0 0%	2 3.8%
Atrial fibrillation	3 50%	0 0%
Back pain	0 0%	1 1.9%
Blood bilirubin increased	0 0%	1 1.9%
Bone pain	0 0%	2 3.8%
Cataract	0 0%	1 1.9%
Creatinine increased	0 0%	1 1.9%
Diarrhea	5 83.3%	1 1.9%
Dizziness	1 16.7%	0 0%
Dry skin	1 16.7%	0 0%
Dyspnea	0 0%	2 3.8%
Edema limbs	2 33.3%	0 0%
Encephalopathy	1 16.7%	0 0%
Eye disorders - Other, specify	0 0%	1 1.9%
Fall	1 16.7%	0 0%
Fatigue	6 100%	5 9.6%
Febrile neutropenia	2 33.3%	1 1.9%
Fracture	0 0%	1 1.9%
Gait disturbance	1 16.7%	0 0%
Gastrointestinal disorders - Other, specify	0 0%	1 1.9%
Generalized muscle weakness	1 16.7%	1 1.9%
Hyperglycemia	2 33.3%	4 7.7%
Hyperkalemia	1 16.7%	1 1.9%
Hypertension	2 33.3%	1 1.9%
Hypoalbuminemia	0 0%	1 1.9%
Hypokalemia	0 0%	4 7.7%
Hyponatremia	3 50%	1 1.9%
Hypophosphatemia	1 16.7%	0 0%
Hypotension	2 33.3%	4 7.7%
Hypoxia	1 16.7%	1 1.9%
INR increased	0 0%	1 1.9%
Infections and infestations - Other, specify	3 50%	4 7.7%
Infusion related reaction	0 0%	3 5.8%
Insomnia	0 0%	2 3.8%
Lung infection	3 50%	5 9.6%
Lymphocyte count decreased	14 233.3%	13 25%
Multi-organ failure	0 0%	1 1.9%
Muscle weakness lower limb	2 33.3%	0 0%
Muscle weakness trunk	0 0%	1 1.9%
Musculoskeletal and connective tiss disorder - Other	1 16.7%	0 0%
Nausea	1 16.7%	0 0%
Neck pain	0 0%	1 1.9%
Neuralgia	0 0%	1 1.9%
Neutrophil count decreased	8 133.3%	5 9.6%
Osteonecrosis of jaw	1 16.7%	0 0%
Pain	0 0%	1 1.9%
Pain in extremity	1 16.7%	0 0%
Peripheral motor neuropathy	1 16.7%	4 7.7%
Peripheral sensory neuropathy	4 66.7%	6 11.5%
Platelet count decreased	10 166.7%	10 19.2%
Pneumonitis	0 0%	1 1.9%
Portal vein thrombosis	0 0%	1 1.9%
Pulmonary edema	1 16.7%	0 0%
Rash acneiform	1 16.7%	0 0%
Rash maculo-papular	2 33.3%	3 5.8%
Resp, thoracic and mediastinal disorders - Other	0 0%	1 1.9%
Respiratory failure	2 33.3%	1 1.9%
Sepsis	2 33.3%	1 1.9%
Skin infection	0 0%	1 1.9%
Stroke	0 0%	1 1.9%
Supraventricular tachycardia	0 0%	1 1.9%
Syncope	1 16.7%	2 3.8%
Thromboembolic event	4 66.7%	1 1.9%
Tremor	1 16.7%	0 0%
Urinary tract infection	2 33.3%	0 0%
Urine output decreased	0 0%	1 1.9%
Vomiting	1 16.7%	0 0%
Weight loss	0 0%	1 1.9%
White blood cell decreased	4 66.7%	5 9.6%

4. Secondary Outcome

Title	Overall Survival
Description	From date of registration to date of death due to any cause
Time Frame	Up to 6 years post registration

Outcome Measure Data

Analysis Population Description

Eligible and evaluable participants

Arm/Group Title	Arm I (Bortezomib, Lenalidomide, Dexamethasone)	Arm II (Bortezomib, Lenalidomide, Dexamethasone, Elotuzumab)
Arm/Group Description	INDUCTION: Participants receive bortezomib SC or IV on days 1, 4, 8, and 11; lenalidomide PO QD on days 1-14; and dexamethasone PO or IV on days 1, 2, 4, 5, 8, 9, 11, and 12. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity (participants who received a course of chemotherapy prior to registration will begin protocol treatment with course 2 and receive a total of 7 courses of protocol therapy). MAINTENANCE: Participants receive bortezomib SC or IV on days 1, 8, and 15; lenalidomide PO QD on days 1-21; and dexamethasone PO on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Bortezomib: Given SC or IV Dexamethasone: Given PO or IV Laboratory Biomarker Analysis: Correlative studies Lenalidomide: Given PO	INDUCTION: Participants receive bortezomib, lenalidomide, and dexamethasone as in Arm I. Participants also receive elotuzumab IV on days 1, 8, and 15 of courses 1 and 2 and on days 1 and 11 of courses 3-8. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE:Participants receive bortezomib, lenalidomide, and dexamethasone as in Arm I. Participants also receive elotuzumab IV on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Bortezomib: Given SC or IV Dexamethasone: Given PO or IV Elotuzumab: Given IV Laboratory Biomarker Analysis: Correlative studies Lenalidomide: Given PO
Measure Participants	52	48
Median (95% Confidence Interval) [months]	NA	68

5. Secondary Outcome

Title	Response (Partial Response [PR] or Better) Rate
Description	Percentage of participants with PR or better to treatment per the International Uniform Response Criteria for Multiple Myeloma stringent Complete Response- CR criteria + normal serum free light chain (FLC) ratio + absence of clonal cells in bone marrow (BM) by immunohistochemistry or immunofluorescence CR- Negative immunofixation (IFX) on serum & urine M proteins + <5% plasma cells in BM + disappearance of soft tissue plasmocytomas (STP) very good PR- PR criteria + serum & urine M proteins detectable by IFX but not on electrophoresis or >=90% reduction (RED) in serum M protein & urine M protein <100 g/24 hrs PR- >=50% RED in size of STP, if present at baseline & >=50% RED in plasma cells, if >=30% plasma cells in BM at baseline: & RED in serum M protein of >=50% & in urine M protein of >= 90% or to 200 mg/24hr OR if serum M protein <1 g/dL, urine M protein <200 mg/24 hrs, & involved serum FLC level >= 10 mg/dl at baseline: >= 50% RED in (involved-uninvolved) serum FLC levels
Time Frame	Up to 6 years post registration

Outcome Measure Data

Analysis Population Description

Eligible participants assessable for response at follow up. 1 participant on Arm II was not assessable for RR.

Arm/Group Title	Arm I (Bortezomib, Lenalidomide, Dexamethasone)	Arm II (Bortezomib, Lenalidomide, Dexamethasone, Elotuzumab)
Arm/Group Description	INDUCTION: Participants receive bortezomib SC or IV on days 1, 4, 8, and 11; lenalidomide PO QD on days 1-14; and dexamethasone PO or IV on days 1, 2, 4, 5, 8, 9, 11, and 12. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity (participants who received a course of chemotherapy prior to registration will begin protocol treatment with course 2 and receive a total of 7 courses of protocol therapy). MAINTENANCE: Participants receive bortezomib SC or IV on days 1, 8, and 15; lenalidomide PO QD on days 1-21; and dexamethasone PO on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Bortezomib: Given SC or IV Dexamethasone: Given PO or IV Laboratory Biomarker Analysis: Correlative studies Lenalidomide: Given PO	INDUCTION: Participants receive bortezomib, lenalidomide, and dexamethasone as in Arm I. Participants also receive elotuzumab IV on days 1, 8, and 15 of courses 1 and 2 and on days 1 and 11 of courses 3-8. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE:Participants receive bortezomib, lenalidomide, and dexamethasone as in Arm I. Participants also receive elotuzumab IV on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Bortezomib: Given SC or IV Dexamethasone: Given PO or IV Elotuzumab: Given IV Laboratory Biomarker Analysis: Correlative studies Lenalidomide: Given PO
Measure Participants	52	47
Number (95% Confidence Interval) [Percentage of participants]	88 1466.7%	83 159.6%

Adverse Events

Time Frame	Duration of treatment and follow up until death or 6 years post registration, whichever occurs first.
Adverse Event Reporting Description	6 participants in Phase I and 100 participants in Phase II were evaluable and assessed for AEs.
Arm/Group Title	Phase I Dose Level 1 (Elotuzumab, 10mg, and Bortezomib, Lenali		Arm I (Bortezomib, Lenalidomide, Dexamethasone)		Arm II (Bortezomib, Lenalidomide, Dexamethasone, Elotuzumab)
Arm/Group Description	INDUCTION: Participants receive bortezomib subcutaneously (SC) or intravenously (IV) on days 1, 4, 8, and 11; lenalidomide orally (PO) once daily (QD) on days 1-14; and dexamethasone PO or IV on days 1, 2, 4, 5, 8, 9, 11, and 12 (and on day 15 of courses 1 and 2 only). Participants also receive elotuzumab IV on days 1, 8, and 15 of courses 1 and 2 and on days 1 and 11 of courses 3-8. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Participants receive bortezomib SC or IV on days 1, 8, and 15; lenalidomide PO QD on days 1-21; dexamethasone PO on days 1, 8, and 15; and elotuzumab IV on days 1 and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.		INDUCTION: Participants receive bortezomib SC or IV on days 1, 4, 8, and 11; lenalidomide PO QD on days 1-14; and dexamethasone PO or IV on days 1, 2, 4, 5, 8, 9, 11, and 12. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity (participants who received a course of chemotherapy prior to registration will begin protocol treatment with course 2 and receive a total of 7 courses of protocol therapy). MAINTENANCE: Participants receive bortezomib SC or IV on days 1, 8, and 15; lenalidomide PO QD on days 1-21; and dexamethasone PO on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Bortezomib: Given SC or IV Dexamethasone: Given PO or IV Lenalidomide: Given PO		INDUCTION: Participants receive bortezomib, lenalidomide, and dexamethasone as in Arm I. Participants also receive elotuzumab IV on days 1, 8, and 15 of courses 1 and 2 and on days 1 and 11 of courses 3-8. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Participants receive bortezomib, lenalidomide, and dexamethasone as in Arm I. Participants also receive elotuzumab IV on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Bortezomib: Given SC or IV Dexamethasone: Given PO or IV Elotuzumab: Given IV Lenalidomide: Given PO
All Cause Mortality
	Phase I Dose Level 1 (Elotuzumab, 10mg, and Bortezomib, Lenali		Arm I (Bortezomib, Lenalidomide, Dexamethasone)		Arm II (Bortezomib, Lenalidomide, Dexamethasone, Elotuzumab)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/6 (33.3%)		19/52 (36.5%)		16/48 (33.3%)
Serious Adverse Events
	Phase I Dose Level 1 (Elotuzumab, 10mg, and Bortezomib, Lenali		Arm I (Bortezomib, Lenalidomide, Dexamethasone)		Arm II (Bortezomib, Lenalidomide, Dexamethasone, Elotuzumab)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/6 (50%)		6/52 (11.5%)		24/48 (50%)
Blood and lymphatic system disorders
Anemia	0/6 (0%)		0/52 (0%)		4/48 (8.3%)
Febrile neutropenia	0/6 (0%)		1/52 (1.9%)		1/48 (2.1%)
Cardiac disorders
Atrial fibrillation	0/6 (0%)		1/52 (1.9%)		1/48 (2.1%)
Sinus bradycardia	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Gastrointestinal disorders
Diarrhea	0/6 (0%)		0/52 (0%)		3/48 (6.3%)
Nausea	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Vomiting	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
General disorders
Chills	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Edema limbs	0/6 (0%)		0/52 (0%)		2/48 (4.2%)
Flu like symptoms	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Infusion related reaction	0/6 (0%)		0/52 (0%)		2/48 (4.2%)
Malaise	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Multi-organ failure	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Pain	0/6 (0%)		0/52 (0%)		2/48 (4.2%)
Infections and infestations
Infections and infestations-Other	1/6 (16.7%)		1/52 (1.9%)		5/48 (10.4%)
Lung infection	0/6 (0%)		0/52 (0%)		7/48 (14.6%)
Sepsis	0/6 (0%)		1/52 (1.9%)		1/48 (2.1%)
Skin infection	1/6 (16.7%)		0/52 (0%)		0/48 (0%)
Urinary tract infection	0/6 (0%)		0/52 (0%)		3/48 (6.3%)
Injury, poisoning and procedural complications
Fall	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Spinal fracture	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Investigations
Alanine aminotransferase increased	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Aspartate aminotransferase increased	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Blood bilirubin increased	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Creatinine increased	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
INR increased	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Lymphocyte count decreased	0/6 (0%)		0/52 (0%)		2/48 (4.2%)
Neutrophil count decreased	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Platelet count decreased	0/6 (0%)		0/52 (0%)		4/48 (8.3%)
Urine output decreased	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
White blood cell decreased	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Metabolism and nutrition disorders
Hyperglycemia	0/6 (0%)		0/52 (0%)		2/48 (4.2%)
Hyperkalemia	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Hypoalbuminemia	0/6 (0%)		0/52 (0%)		2/48 (4.2%)
Hypocalcemia	0/6 (0%)		0/52 (0%)		3/48 (6.3%)
Hypokalemia	0/6 (0%)		0/52 (0%)		2/48 (4.2%)
Hypophosphatemia	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Musculoskeletal and connective tissue disorders
Back pain	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Generalized muscle weakness	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Muscle weakness lower limb	0/6 (0%)		0/52 (0%)		2/48 (4.2%)
Muscle weakness trunk	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Muscle weakness upper limb	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Neck pain	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Osteonecrosis of jaw	0/6 (0%)		1/52 (1.9%)		0/48 (0%)
Pain in extremity	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified - Other	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Treatment related secondary malignancy	2/6 (33.3%)		0/52 (0%)		0/48 (0%)
Nervous system disorders
Nervous system disorders-Other	1/6 (16.7%)		0/52 (0%)		0/48 (0%)
Neuralgia	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Presyncope	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Stroke	0/6 (0%)		1/52 (1.9%)		1/48 (2.1%)
Syncope	0/6 (0%)		0/52 (0%)		3/48 (6.3%)
Renal and urinary disorders
Cystitis noninfective	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Reproductive system and breast disorders
Pelvic pain	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Respiratory, thoracic and mediastinal disorders
Atelectasis	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Dyspnea	0/6 (0%)		0/52 (0%)		3/48 (6.3%)
Hypoxia	0/6 (0%)		1/52 (1.9%)		2/48 (4.2%)
Pneumonitis	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Productive cough	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Pulmonary edema	0/6 (0%)		1/52 (1.9%)		0/48 (0%)
Respiratory failure	0/6 (0%)		2/52 (3.8%)		1/48 (2.1%)
Wheezing	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Skin and subcutaneous tissue disorders
Erythroderma	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Rash maculo-papular	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Vascular disorders
Hypotension	0/6 (0%)		1/52 (1.9%)		1/48 (2.1%)
Thromboembolic event	1/6 (16.7%)		1/52 (1.9%)		1/48 (2.1%)
Other (Not Including Serious) Adverse Events
	Phase I Dose Level 1 (Elotuzumab, 10mg, and Bortezomib, Lenali		Arm I (Bortezomib, Lenalidomide, Dexamethasone)		Arm II (Bortezomib, Lenalidomide, Dexamethasone, Elotuzumab)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/6 (100%)		52/52 (100%)		47/48 (97.9%)
Blood and lymphatic system disorders
Anemia	1/6 (16.7%)		39/52 (75%)		21/48 (43.8%)
Blood and lymphatic system disorders - Other	1/6 (16.7%)		1/52 (1.9%)		0/48 (0%)
Febrile neutropenia	0/6 (0%)		1/52 (1.9%)		0/48 (0%)
Leukocytosis	1/6 (16.7%)		0/52 (0%)		0/48 (0%)
Cardiac disorders
Atrial fibrillation	0/6 (0%)		3/52 (5.8%)		1/48 (2.1%)
Cardiac disorders-Other	1/6 (16.7%)		0/52 (0%)		0/48 (0%)
Chest pain - cardiac	0/6 (0%)		2/52 (3.8%)		0/48 (0%)
Heart failure	0/6 (0%)		4/52 (7.7%)		0/48 (0%)
Myocardial infarction	0/6 (0%)		1/52 (1.9%)		0/48 (0%)
Palpitations	0/6 (0%)		1/52 (1.9%)		1/48 (2.1%)
Paroxysmal atrial tachycardia	0/6 (0%)		1/52 (1.9%)		0/48 (0%)
Sinus bradycardia	1/6 (16.7%)		4/52 (7.7%)		3/48 (6.3%)
Sinus tachycardia	0/6 (0%)		2/52 (3.8%)		4/48 (8.3%)
Supraventricular tachycardia	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Ear and labyrinth disorders
Ear and labyrinth disorders-Other	1/6 (16.7%)		1/52 (1.9%)		1/48 (2.1%)
Ear pain	0/6 (0%)		3/52 (5.8%)		0/48 (0%)
Hearing impaired	0/6 (0%)		0/52 (0%)		3/48 (6.3%)
Tinnitus	2/6 (33.3%)		3/52 (5.8%)		1/48 (2.1%)
Vertigo	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Endocrine disorders
Cushingoid	0/6 (0%)		1/52 (1.9%)		0/48 (0%)
Endocrine disorders-Other	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Hyperparathyroidism	0/6 (0%)		1/52 (1.9%)		0/48 (0%)
Hyperthyroidism	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Hypothyroidism	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Eye disorders
Blurred vision	2/6 (33.3%)		10/52 (19.2%)		11/48 (22.9%)
Cataract	1/6 (16.7%)		2/52 (3.8%)		2/48 (4.2%)
Conjunctivitis	1/6 (16.7%)		1/52 (1.9%)		1/48 (2.1%)
Dry eye	0/6 (0%)		2/52 (3.8%)		2/48 (4.2%)
Eye disorders-Other	0/6 (0%)		5/52 (9.6%)		6/48 (12.5%)
Flashing lights	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Floaters	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Optic nerve disorder	1/6 (16.7%)		0/52 (0%)		0/48 (0%)
Photophobia	0/6 (0%)		1/52 (1.9%)		0/48 (0%)
Scleral disorder	0/6 (0%)		1/52 (1.9%)		0/48 (0%)
Watering eyes	0/6 (0%)		1/52 (1.9%)		1/48 (2.1%)
Gastrointestinal disorders
Abdominal distension	1/6 (16.7%)		1/52 (1.9%)		2/48 (4.2%)
Abdominal pain	3/6 (50%)		7/52 (13.5%)		7/48 (14.6%)
Bloating	1/6 (16.7%)		2/52 (3.8%)		3/48 (6.3%)
Colitis	0/6 (0%)		1/52 (1.9%)		0/48 (0%)
Constipation	3/6 (50%)		37/52 (71.2%)		24/48 (50%)
Dental caries	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Diarrhea	5/6 (83.3%)		29/52 (55.8%)		24/48 (50%)
Dry mouth	0/6 (0%)		3/52 (5.8%)		8/48 (16.7%)
Dyspepsia	2/6 (33.3%)		12/52 (23.1%)		5/48 (10.4%)
Dysphagia	0/6 (0%)		4/52 (7.7%)		5/48 (10.4%)
Enterocolitis	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Esophagitis	0/6 (0%)		0/52 (0%)		2/48 (4.2%)
Fecal incontinence	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Flatulence	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Gastritis	0/6 (0%)		2/52 (3.8%)		0/48 (0%)
Gastroesophageal reflux disease	3/6 (50%)		7/52 (13.5%)		6/48 (12.5%)
Gastrointestinal disorders-Other	0/6 (0%)		4/52 (7.7%)		3/48 (6.3%)
Gingival pain	0/6 (0%)		1/52 (1.9%)		1/48 (2.1%)
Hemorrhoidal hemorrhage	0/6 (0%)		2/52 (3.8%)		1/48 (2.1%)
Hemorrhoids	0/6 (0%)		1/52 (1.9%)		0/48 (0%)
Ileus	0/6 (0%)		1/52 (1.9%)		0/48 (0%)
Lower gastrointestinal hemorrhage	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Mucositis oral	0/6 (0%)		6/52 (11.5%)		6/48 (12.5%)
Nausea	3/6 (50%)		26/52 (50%)		25/48 (52.1%)
Oral pain	0/6 (0%)		2/52 (3.8%)		0/48 (0%)
Rectal hemorrhage	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Small intestinal obstruction	0/6 (0%)		1/52 (1.9%)		0/48 (0%)
Stomach pain	0/6 (0%)		3/52 (5.8%)		2/48 (4.2%)
Toothache	0/6 (0%)		2/52 (3.8%)		1/48 (2.1%)
Vomiting	3/6 (50%)		8/52 (15.4%)		9/48 (18.8%)
General disorders
Chills	3/6 (50%)		9/52 (17.3%)		8/48 (16.7%)
Edema face	0/6 (0%)		4/52 (7.7%)		3/48 (6.3%)
Edema limbs	6/6 (100%)		33/52 (63.5%)		29/48 (60.4%)
Fatigue	6/6 (100%)		41/52 (78.8%)		34/48 (70.8%)
Fever	3/6 (50%)		11/52 (21.2%)		13/48 (27.1%)
Flu like symptoms	4/6 (66.7%)		0/52 (0%)		3/48 (6.3%)
Gait disturbance	0/6 (0%)		6/52 (11.5%)		2/48 (4.2%)
General disorders and admin site conditions - Other	4/6 (66.7%)		3/52 (5.8%)		3/48 (6.3%)
Infusion related reaction	0/6 (0%)		0/52 (0%)		2/48 (4.2%)
Infusion site extravasation	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Injection site reaction	2/6 (33.3%)		1/52 (1.9%)		3/48 (6.3%)
Irritability	1/6 (16.7%)		1/52 (1.9%)		2/48 (4.2%)
Localized edema	0/6 (0%)		4/52 (7.7%)		1/48 (2.1%)
Malaise	0/6 (0%)		3/52 (5.8%)		2/48 (4.2%)
Non-cardiac chest pain	0/6 (0%)		5/52 (9.6%)		3/48 (6.3%)
Pain	3/6 (50%)		14/52 (26.9%)		14/48 (29.2%)
Hepatobiliary disorders
Portal vein thrombosis	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Immune system disorders
Allergic reaction	0/6 (0%)		1/52 (1.9%)		2/48 (4.2%)
Autoimmune disorder	1/6 (16.7%)		0/52 (0%)		0/48 (0%)
Immune system disorders-Other	2/6 (33.3%)		0/52 (0%)		0/48 (0%)
Infections and infestations
Bladder infection	1/6 (16.7%)		0/52 (0%)		0/48 (0%)
Bronchial infection	2/6 (33.3%)		2/52 (3.8%)		1/48 (2.1%)
Conjunctivitis infective	0/6 (0%)		1/52 (1.9%)		0/48 (0%)
Endocarditis infective	0/6 (0%)		1/52 (1.9%)		0/48 (0%)
Eye infection	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Gum infection	1/6 (16.7%)		1/52 (1.9%)		0/48 (0%)
Infections and infestations-Other	3/6 (50%)		11/52 (21.2%)		5/48 (10.4%)
Lung infection	0/6 (0%)		7/52 (13.5%)		4/48 (8.3%)
Mucosal infection	1/6 (16.7%)		1/52 (1.9%)		2/48 (4.2%)
Nail infection	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Papulopustular rash	0/6 (0%)		1/52 (1.9%)		0/48 (0%)
Peripheral nerve infection	0/6 (0%)		1/52 (1.9%)		0/48 (0%)
Rhinitis infective	0/6 (0%)		1/52 (1.9%)		1/48 (2.1%)
Sepsis	0/6 (0%)		3/52 (5.8%)		0/48 (0%)
Sinusitis	0/6 (0%)		2/52 (3.8%)		2/48 (4.2%)
Skin infection	1/6 (16.7%)		2/52 (3.8%)		3/48 (6.3%)
Soft tissue infection	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Tooth infection	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Upper respiratory infection	5/6 (83.3%)		8/52 (15.4%)		8/48 (16.7%)
Urinary tract infection	1/6 (16.7%)		5/52 (9.6%)		6/48 (12.5%)
Injury, poisoning and procedural complications
Ankle fracture	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Bruising	1/6 (16.7%)		3/52 (5.8%)		6/48 (12.5%)
Burn	0/6 (0%)		1/52 (1.9%)		0/48 (0%)
Fall	2/6 (33.3%)		8/52 (15.4%)		7/48 (14.6%)
Fracture	1/6 (16.7%)		1/52 (1.9%)		2/48 (4.2%)
Hip fracture	0/6 (0%)		1/52 (1.9%)		0/48 (0%)
Injury, poison and procedural complications - Other	2/6 (33.3%)		0/52 (0%)		6/48 (12.5%)
Spinal fracture	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Tracheal obstruction	0/6 (0%)		1/52 (1.9%)		0/48 (0%)
Investigations
Activated partial thromboplastin time prolonged	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Alanine aminotransferase increased	1/6 (16.7%)		15/52 (28.8%)		14/48 (29.2%)
Alkaline phosphatase increased	1/6 (16.7%)		13/52 (25%)		12/48 (25%)
Aspartate aminotransferase increased	1/6 (16.7%)		9/52 (17.3%)		10/48 (20.8%)
Blood bilirubin increased	1/6 (16.7%)		6/52 (11.5%)		1/48 (2.1%)
Cholesterol high	0/6 (0%)		2/52 (3.8%)		4/48 (8.3%)
Creatinine increased	1/6 (16.7%)		14/52 (26.9%)		9/48 (18.8%)
Ejection fraction decreased	0/6 (0%)		1/52 (1.9%)		0/48 (0%)
Electrocardiogram QT corrected interval prolonged	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Hemoglobin increased	0/6 (0%)		1/52 (1.9%)		1/48 (2.1%)
INR increased	0/6 (0%)		1/52 (1.9%)		3/48 (6.3%)
Investigations-Other	1/6 (16.7%)		1/52 (1.9%)		0/48 (0%)
Lymphocyte count decreased	4/6 (66.7%)		24/52 (46.2%)		18/48 (37.5%)
Lymphocyte count increased	0/6 (0%)		1/52 (1.9%)		2/48 (4.2%)
Neutrophil count decreased	2/6 (33.3%)		18/52 (34.6%)		17/48 (35.4%)
Platelet count decreased	3/6 (50%)		30/52 (57.7%)		32/48 (66.7%)
Weight gain	1/6 (16.7%)		8/52 (15.4%)		11/48 (22.9%)
Weight loss	2/6 (33.3%)		9/52 (17.3%)		9/48 (18.8%)
White blood cell decreased	4/6 (66.7%)		25/52 (48.1%)		23/48 (47.9%)
Metabolism and nutrition disorders
Acidosis	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Anorexia	3/6 (50%)		20/52 (38.5%)		17/48 (35.4%)
Dehydration	1/6 (16.7%)		7/52 (13.5%)		10/48 (20.8%)
Glucose intolerance	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Hypercalcemia	0/6 (0%)		6/52 (11.5%)		7/48 (14.6%)
Hyperglycemia	0/6 (0%)		15/52 (28.8%)		17/48 (35.4%)
Hyperkalemia	1/6 (16.7%)		5/52 (9.6%)		4/48 (8.3%)
Hypermagnesemia	0/6 (0%)		1/52 (1.9%)		1/48 (2.1%)
Hypernatremia	0/6 (0%)		6/52 (11.5%)		2/48 (4.2%)
Hypertriglyceridemia	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Hyperuricemia	0/6 (0%)		3/52 (5.8%)		0/48 (0%)
Hypoalbuminemia	3/6 (50%)		15/52 (28.8%)		20/48 (41.7%)
Hypocalcemia	1/6 (16.7%)		21/52 (40.4%)		21/48 (43.8%)
Hypoglycemia	2/6 (33.3%)		6/52 (11.5%)		7/48 (14.6%)
Hypokalemia	2/6 (33.3%)		18/52 (34.6%)		18/48 (37.5%)
Hypomagnesemia	0/6 (0%)		6/52 (11.5%)		5/48 (10.4%)
Hyponatremia	2/6 (33.3%)		14/52 (26.9%)		14/48 (29.2%)
Hypophosphatemia	0/6 (0%)		6/52 (11.5%)		1/48 (2.1%)
Metabolism and nutrition disorders - Other, specify	0/6 (0%)		1/52 (1.9%)		1/48 (2.1%)
Obesity	0/6 (0%)		1/52 (1.9%)		0/48 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/6 (16.7%)		12/52 (23.1%)		11/48 (22.9%)
Arthritis	1/6 (16.7%)		4/52 (7.7%)		0/48 (0%)
Back pain	4/6 (66.7%)		19/52 (36.5%)		20/48 (41.7%)
Bone pain	1/6 (16.7%)		11/52 (21.2%)		9/48 (18.8%)
Buttock pain	1/6 (16.7%)		1/52 (1.9%)		0/48 (0%)
Chest wall pain	0/6 (0%)		3/52 (5.8%)		4/48 (8.3%)
Flank pain	0/6 (0%)		3/52 (5.8%)		2/48 (4.2%)
Generalized muscle weakness	2/6 (33.3%)		8/52 (15.4%)		11/48 (22.9%)
Joint effusion	1/6 (16.7%)		1/52 (1.9%)		0/48 (0%)
Muscle weakness lower limb	2/6 (33.3%)		6/52 (11.5%)		4/48 (8.3%)
Muscle weakness right-sided	0/6 (0%)		1/52 (1.9%)		0/48 (0%)
Muscle weakness upper limb	0/6 (0%)		1/52 (1.9%)		2/48 (4.2%)
Musculoskeletal and connective tiss disorder - Other	3/6 (50%)		5/52 (9.6%)		3/48 (6.3%)
Myalgia	0/6 (0%)		13/52 (25%)		10/48 (20.8%)
Neck pain	1/6 (16.7%)		2/52 (3.8%)		6/48 (12.5%)
Osteonecrosis of jaw	0/6 (0%)		1/52 (1.9%)		0/48 (0%)
Osteoporosis	0/6 (0%)		2/52 (3.8%)		0/48 (0%)
Pain in extremity	4/6 (66.7%)		21/52 (40.4%)		25/48 (52.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified - Other	0/6 (0%)		1/52 (1.9%)		2/48 (4.2%)
Nervous system disorders
Akathisia	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Ataxia	0/6 (0%)		1/52 (1.9%)		3/48 (6.3%)
Cognitive disturbance	0/6 (0%)		1/52 (1.9%)		0/48 (0%)
Concentration impairment	0/6 (0%)		1/52 (1.9%)		0/48 (0%)
Depressed level of consciousness	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Dizziness	3/6 (50%)		22/52 (42.3%)		19/48 (39.6%)
Dysesthesia	0/6 (0%)		1/52 (1.9%)		0/48 (0%)
Dysgeusia	0/6 (0%)		13/52 (25%)		10/48 (20.8%)
Dysphasia	0/6 (0%)		0/52 (0%)		2/48 (4.2%)
Encephalopathy	0/6 (0%)		2/52 (3.8%)		0/48 (0%)
Headache	2/6 (33.3%)		16/52 (30.8%)		14/48 (29.2%)
Hypersomnia	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Ischemia cerebrovascular	1/6 (16.7%)		1/52 (1.9%)		0/48 (0%)
Memory impairment	1/6 (16.7%)		2/52 (3.8%)		6/48 (12.5%)
Movements involuntary	1/6 (16.7%)		0/52 (0%)		1/48 (2.1%)
Nervous system disorders-Other	0/6 (0%)		1/52 (1.9%)		0/48 (0%)
Neuralgia	0/6 (0%)		1/52 (1.9%)		2/48 (4.2%)
Paresthesia	1/6 (16.7%)		5/52 (9.6%)		4/48 (8.3%)
Peripheral motor neuropathy	1/6 (16.7%)		6/52 (11.5%)		13/48 (27.1%)
Peripheral sensory neuropathy	5/6 (83.3%)		38/52 (73.1%)		35/48 (72.9%)
Presyncope	0/6 (0%)		2/52 (3.8%)		2/48 (4.2%)
Radiculitis	1/6 (16.7%)		4/52 (7.7%)		0/48 (0%)
Seizure	0/6 (0%)		1/52 (1.9%)		0/48 (0%)
Sinus pain	0/6 (0%)		1/52 (1.9%)		0/48 (0%)
Somnolence	0/6 (0%)		1/52 (1.9%)		0/48 (0%)
Spasticity	0/6 (0%)		1/52 (1.9%)		0/48 (0%)
Syncope	0/6 (0%)		3/52 (5.8%)		2/48 (4.2%)
Tremor	1/6 (16.7%)		4/52 (7.7%)		6/48 (12.5%)
Psychiatric disorders
Agitation	0/6 (0%)		1/52 (1.9%)		4/48 (8.3%)
Anxiety	2/6 (33.3%)		8/52 (15.4%)		10/48 (20.8%)
Confusion	0/6 (0%)		2/52 (3.8%)		3/48 (6.3%)
Depression	0/6 (0%)		5/52 (9.6%)		10/48 (20.8%)
Insomnia	3/6 (50%)		16/52 (30.8%)		19/48 (39.6%)
Personality change	0/6 (0%)		1/52 (1.9%)		0/48 (0%)
Restlessness	1/6 (16.7%)		1/52 (1.9%)		1/48 (2.1%)
Renal and urinary disorders
Acute kidney injury	0/6 (0%)		6/52 (11.5%)		1/48 (2.1%)
Chronic kidney disease	0/6 (0%)		1/52 (1.9%)		2/48 (4.2%)
Hematuria	0/6 (0%)		1/52 (1.9%)		3/48 (6.3%)
Proteinuria	0/6 (0%)		4/52 (7.7%)		4/48 (8.3%)
Renal and urinary disorders-Other	0/6 (0%)		1/52 (1.9%)		1/48 (2.1%)
Renal calculi	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Urinary frequency	0/6 (0%)		4/52 (7.7%)		1/48 (2.1%)
Urinary incontinence	1/6 (16.7%)		1/52 (1.9%)		2/48 (4.2%)
Urinary retention	0/6 (0%)		2/52 (3.8%)		4/48 (8.3%)
Urinary tract pain	1/6 (16.7%)		1/52 (1.9%)		2/48 (4.2%)
Urinary urgency	0/6 (0%)		1/52 (1.9%)		1/48 (2.1%)
Urine discoloration	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Reproductive system and breast disorders
Erectile dysfunction	0/6 (0%)		2/52 (3.8%)		2/48 (4.2%)
Pelvic pain	0/6 (0%)		1/52 (1.9%)		2/48 (4.2%)
Prostatic obstruction	0/6 (0%)		1/52 (1.9%)		0/48 (0%)
Testicular pain	0/6 (0%)		1/52 (1.9%)		1/48 (2.1%)
Vaginal discharge	0/6 (0%)		2/52 (3.8%)		0/48 (0%)
Vaginal hemorrhage	1/6 (16.7%)		0/52 (0%)		0/48 (0%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	0/6 (0%)		3/52 (5.8%)		3/48 (6.3%)
Aspiration	1/6 (16.7%)		0/52 (0%)		0/48 (0%)
Atelectasis	1/6 (16.7%)		0/52 (0%)		0/48 (0%)
Cough	5/6 (83.3%)		18/52 (34.6%)		22/48 (45.8%)
Dyspnea	2/6 (33.3%)		21/52 (40.4%)		19/48 (39.6%)
Epistaxis	0/6 (0%)		3/52 (5.8%)		2/48 (4.2%)
Hiccups	0/6 (0%)		1/52 (1.9%)		0/48 (0%)
Hoarseness	0/6 (0%)		3/52 (5.8%)		1/48 (2.1%)
Hypoxia	0/6 (0%)		4/52 (7.7%)		1/48 (2.1%)
Nasal congestion	2/6 (33.3%)		8/52 (15.4%)		7/48 (14.6%)
Pharyngeal mucositis	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Pleural effusion	0/6 (0%)		2/52 (3.8%)		2/48 (4.2%)
Pleuritic pain	0/6 (0%)		2/52 (3.8%)		0/48 (0%)
Pneumonitis	1/6 (16.7%)		1/52 (1.9%)		0/48 (0%)
Postnasal drip	1/6 (16.7%)		2/52 (3.8%)		2/48 (4.2%)
Productive cough	1/6 (16.7%)		4/52 (7.7%)		11/48 (22.9%)
Pulmonary edema	0/6 (0%)		1/52 (1.9%)		0/48 (0%)
Resp, thoracic and mediastinal disorders - Other	1/6 (16.7%)		0/52 (0%)		1/48 (2.1%)
Retinoic acid syndrome	0/6 (0%)		1/52 (1.9%)		0/48 (0%)
Sleep apnea	1/6 (16.7%)		1/52 (1.9%)		2/48 (4.2%)
Sore throat	0/6 (0%)		5/52 (9.6%)		4/48 (8.3%)
Wheezing	1/6 (16.7%)		2/52 (3.8%)		1/48 (2.1%)
Skin and subcutaneous tissue disorders
Alopecia	0/6 (0%)		2/52 (3.8%)		6/48 (12.5%)
Dry skin	1/6 (16.7%)		7/52 (13.5%)		8/48 (16.7%)
Erythema multiforme	1/6 (16.7%)		0/52 (0%)		5/48 (10.4%)
Hirsutism	0/6 (0%)		0/52 (0%)		2/48 (4.2%)
Hyperhidrosis	0/6 (0%)		3/52 (5.8%)		7/48 (14.6%)
Nail discoloration	0/6 (0%)		1/52 (1.9%)		1/48 (2.1%)
Nail ridging	0/6 (0%)		0/52 (0%)		1/48 (2.1%)
Periorbital edema	0/6 (0%)		1/52 (1.9%)		1/48 (2.1%)
Pruritus	3/6 (50%)		6/52 (11.5%)		6/48 (12.5%)
Purpura	1/6 (16.7%)		0/52 (0%)		1/48 (2.1%)
Rash acneiform	1/6 (16.7%)		3/52 (5.8%)		2/48 (4.2%)
Rash maculo-papular	1/6 (16.7%)		18/52 (34.6%)		12/48 (25%)
Skin and subcutaneous tissue disorders - Other	2/6 (33.3%)		6/52 (11.5%)		5/48 (10.4%)
Skin hyperpigmentation	1/6 (16.7%)		1/52 (1.9%)		2/48 (4.2%)
Skin ulceration	0/6 (0%)		3/52 (5.8%)		1/48 (2.1%)
Urticaria	0/6 (0%)		1/52 (1.9%)		1/48 (2.1%)
Surgical and medical procedures
Surgical and medical procedures-Other	1/6 (16.7%)		1/52 (1.9%)		2/48 (4.2%)
Vascular disorders
Flushing	0/6 (0%)		0/52 (0%)		7/48 (14.6%)
Hematoma	0/6 (0%)		2/52 (3.8%)		0/48 (0%)
Hot flashes	0/6 (0%)		2/52 (3.8%)		6/48 (12.5%)
Hypertension	1/6 (16.7%)		21/52 (40.4%)		17/48 (35.4%)
Hypotension	1/6 (16.7%)		13/52 (25%)		14/48 (29.2%)
Superficial thrombophlebitis	0/6 (0%)		1/52 (1.9%)		1/48 (2.1%)
Thromboembolic event	2/6 (33.3%)		6/52 (11.5%)		6/48 (12.5%)
Vascular disorders-Other	0/6 (0%)		0/52 (0%)		2/48 (4.2%)

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.