Ixazomib Citrate, Lenalidomide, Dexamethasone, and Zoledronic Acid or Zoledronic Acid Alone After Radiation Therapy in Treating Patients With Solitary Plasmacytoma of Bone

Sponsor

Alliance for Clinical Trials in Oncology (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT02516423

Collaborator

National Cancer Institute (NCI) (NIH), Millennium Pharmaceuticals, Inc. (Industry), Biologics, Inc. (Industry)

Enrollment

388

Locations

Arms

Patients Per Site

Study Details

Study Description

Brief Summary

This randomized phase III trial compares ixazomib citrate, lenalidomide, dexamethasone and zoledronic acid with zoledronic acid alone to see how well they work when given after radiation therapy in treating patients with solitary plasmacytoma of bone. Ixazomib citrate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Lenalidomide may help the immune system kill abnormal blood cells or cancer cells. Dexamethasone is a drug used in chemotherapy that may cause tumor cells to die. Zoledronic acid may prevent bone fractures and reduce bone pain, and may also improve survival. Standard treatment for this cancer is radiation therapy alone. It is not yet known whether ixazomib citrate, lenalidomide, dexamethasone and zoledronic acid or zoledronic acid alone is more effective, and whether adding these treatments after radiation therapy is more effective than radiation therapy alone in treating patients with solitary plasmacytoma of bone.

Condition or Disease	Intervention/Treatment	Phase
Solitary Osseous Plasmacytoma	Drug: ixazomib Drug: lenalidomide Drug: dexamethasone Drug: zoledronic acid	Phase 3

Detailed Description

This phase III randomized clinical trial was designed to assess the impact of the addition of ixazomib, lenalidomide, and dexamethasone to zoledronic acid the multiple myeloma progression rate at 5 years. A dynamic allocation procedure will be used to allocate an equal number of patients to each of the treatment arms. This procedure will balance the number of patients which falls into each of the following categories between the two treatment arms:

% of abnormal plasma cells in the bone marrow: 5-9%
age < 60; % of abnormal plasma cells in the bone marrow < 5%; and monoclonal protein/clonal light chains present in the blood or urine
age < 60; % of abnormal plasma cells in the bone marrow < 5% and no monoclonal protein/clonal light chains present in the blood or urine, (MRD+) minimal residual disease
age ≥ 60; % of abnormal plasma cells in the bone marrow < 5%; and monoclonal protein/clonal light chains present in the blood or urine
age ≥ 60; % of abnormal plasma cells in the bone marrow < 5% and no monoclonal protein/clonal light chains present in the blood or urine, (MRD+) minimal residual disease

The primary and secondary objectives are described below.

Primary objective

To assess whether ixazomib, lenalidomide, dexamethasone with zoledronic acid is more promising than zoledronic acid alone in increasing the time before progression to multiple myeloma.

Secondary objectives

To assess changes in minimal residual disease [MRD] by flow cytometry from study entry, at the completion of treatment, and at 1 year post registration.
To assess whether ixazomib, lenalidomide, dexamethasone with zoledronic acid is more promising than zoledronic acid alone in extending overall survival.
To examine the pharmacodynamics effects of treatment on biochemical markers of bone formation (osteocalcin bone-specific alkaline phosphatase), resorption (serum CTX), and metabolism (OPG).

Follow-up requirements after documentation of progression to multiple myeloma includes a maximum of five years following registration.

Study Design

Study Type:

Interventional

Actual Enrollment :

11 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Solitary Plasmacytoma of Bone: Randomized Phase III Trial to Evaluate Treatment With Adjuvant Systemic Treatment and Zoledronic Acid Versus Zoledronic Acid After Definite Radiation Therapy

Actual Study Start Date :

Dec 1, 2015

Anticipated Primary Completion Date :

Sep 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ixazomib + lenalidomide + dexamethasone + zoledronic acid Patients receive 4 mg ixazomib by mouth on days 1, 8 and 15. Patients also receive 15 mg lenalidomide by mouth on days 1-21, 12 mg dexamethasone by mouth on days 1, 8, 15, and 22 and zoledronic acid (dose based on creatinine clearance on day 1) IV infusion on day 1. Patients receive treatment every 28 days for a maximum of 6 cycles.	Drug: ixazomib oral Drug: lenalidomide oral Drug: dexamethasone oral Drug: zoledronic acid IV
Active Comparator: zoledronic acid Patients receive zoledronic acid (dose based on creatinine clearance on day 1) IV on day 1. Patients receive treatment every 28 days for a maximum of 6 cycles.	Drug: zoledronic acid IV

Arm

Intervention/Treatment

Experimental: ixazomib + lenalidomide + dexamethasone + zoledronic acid

Patients receive 4 mg ixazomib by mouth on days 1, 8 and 15. Patients also receive 15 mg lenalidomide by mouth on days 1-21, 12 mg dexamethasone by mouth on days 1, 8, 15, and 22 and zoledronic acid (dose based on creatinine clearance on day 1) IV infusion on day 1. Patients receive treatment every 28 days for a maximum of 6 cycles.

Drug: ixazomib

oral

Drug: lenalidomide

oral

Drug: dexamethasone

oral

Drug: zoledronic acid

Active Comparator: zoledronic acid

Patients receive zoledronic acid (dose based on creatinine clearance on day 1) IV on day 1. Patients receive treatment every 28 days for a maximum of 6 cycles.

Drug: zoledronic acid

Outcome Measures

Primary Outcome Measures

Progression-free survival rate [at 5 years]

Secondary Outcome Measures

Changes in minimal residual disease from study entry to the completion of adjuvant treatment (approximately six months post-registration) and at 1 year post-registration [at 6 and 12 months post-registration]
Clinical response rate at 12 months post-registration using whole body PET/CT [at 12 months post-registration]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Pre-registration eligibility criteria (Step 0)

Documentation of Disease: Histologic Documentation of Solitary Bone Plasmacytoma
For patients pre-registering after the completion of radiation therapy, documentation of a bone marrow aspirate and biopsy containing <10% clonal plasma cells done at most 28 days prior to start of radiation therapy
For patients pre-registering before the start of radiation therapy, radiation therapy scheduled to begin at most 28 days after a bone marrow aspirate and biopsy were performed containing <10% clonal plasma cells
Participants must have disease that is measurable by either serum or urine evaluation of the monoclonal component or by assay of serum free light chains or by minimal residual detection. Measurable disease is defined as one or more of the following:

serum M protein > 0.5 G/DL, or
urine M protein >200 MG/24H, and/or
serum FLC assay: involved FLC level > 10 MG/DL with abnormal serum FLC ratio
≥ 50 Plasma cells detectable by multicolor flow cytometry, at a sensitive level of 10^-4

Age ≥ 18 years
ECOG Performance Status 0-2

Registration Eligibility Criteria (Step 1)

Documentation of Disease:
No lytic lesions on skeletal survey and whole body PET/CT other than a single lesion associated with solitary bone plasmacytoma within 28 days prior to registration.
Participants must have disease that is measurable by either serum or urine evaluation of the monoclonal component or by assay of serum free light chains or by minimal residual detection. Measurable disease is defined as one or more of the following:

serum M protein > 0.5 G/DL, or
urine M protein >200 MG/24H, and/or
serum FLC assay: involved FLC level > 10 MG/DL with abnormal serum FLC ratio
≥ 50 Plasma cells detectable by multicolor flow cytometry, at a sensitive level of 10^-4

Prior Treatment
No major surgery within 21 days of registration with stabilization or resolution of surgical adverse events.
No investigational agent within 21 days prior to registration
No ongoing therapy with corticosteroids greater than 10 mg of prednisone or its equivalent per day. Please note: Inhaled and topical steroids are permitted.
No prior proteasome inhibitor or IMiD use.
Prior bisphosphonate use is permitted.
For all patients:

Radiation dose should range from 4500 cGy to 6000 cGy
No treatment for this disease following radiation therapy
Registration must be completed within 90 days of completion of radiation therapy.

Not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown and an agent that has known genotoxic, mutagenic and teratogenic effects.
Females of childbearing potential (FCBP), defined as a sexually mature female who

has not undergone a hysterectomy or bilateral oophorectomy or 2) has not been naturally postmenopausal for at least 24 consecutive months that is, has not had menses at any time in the preceding 24 consecutive months:

must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to and again within 24 hours of starting lenalidomide.
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 she starts taking lenalidomide.
must 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 vasectomy.
ECOG Performance Status 0-2
Required Initial Laboratory Values within 14 days of registration:
Absolute Neutrophil Count (ANC) ≥ 1,500/mm^3
Platelet Count ≥ 75,000/mm^3
Hemoglobin ≥ 10 g/dL
Serum Creatinine < 2.0 mg/dL [176.8 µmol/liter]
Serum calcium ≤ 11.5 mg/dL
Calc. Creatinine Clearance > 50 mL/min
Bilirubin ≤ 1.5 x upper limits of normal (ULN)
AST ≤ 2.5 x upper limits of normal (ULN)
Intercurrent or Recent Illness
If history of prior malignancy, subject should be in complete remission for ≥ 5 years at the time of registration (with the exception of basal cell or squamous cell carcinoma of the skin treated with local resection).
HIV + patients are eligible provided they meet the other eligibility criteria and:

CD4+ cells are ≥ 250/mm^3
There is no history of AIDS defining conditions other than historically low CD4+ cell count.
The following antiretroviral agents are not allowed: zidovudine, stavudine, protease inhibitors, combination pills with pharmacologic boosters.
Recommended antiretroviral regimens to avoid PK interactions include strand integrase inhibitors with nucleoside and non-nucleoside reverse transcriptase inhibitors (for example, dolutegravir given with tenofovir and emtricitabine).

Patients with HBV infection are eligible provided they meet the other eligibility criteria and:

There is no evidence of hepatic damage related to HBV infection.
They have had consistently suppressed HBV viral load to undetectable levels by PCR for a minimum of 12 months.

Patients with HCV infection are eligible provided they meet the other eligibility criteria and:

They have previously undergone curative therapy and have no evidence of active HCV infection.
They have no evidence of liver damage owing to prior HCV infection.

Patients with active HCV infection should be referred for HCV treatment and standard radiotherapy for the plasmacytoma.

Patients cannot have:

Known allergy to boron or excipients in the formulation.
Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of study drugs including difficulty swallowing.
Infection requiring systemic antibiotic therapy or other serious infection within 14 days before registration.
Diarrhea ≥ Grade 1, based on the NCI CTCAE categorization within 14 days of registration
Life-threatening illness unrelated to cancer
The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide, pomalidomide, or similar drugs.

Peripheral Neuropathy: ≤ Grade 2 Peripheral Neuropathy
Adequate cardiac function, defined as:
No cardiac arrhythmias within 182 days of registration.
No congestive heart failure (CHF) within 182 days of registration.
No angina or myocardial infarction within 182 days of registration. In view of potential cardiac risk with lenalidomide, patients with stable angina will be excluded.
Concomitant Treatment: Patients cannot be on systemic treatment with strong inhibitors of CYP1A2 (fluvoxamine, enoxacin), strong inhibitors of CYP3A (clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone) or strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital) within 14 days of registration.
QT c< 470 milliseconds (msec) on a 12-lead ECG ≤ 28 days before registration
Dental evaluation within 35 days of registration: Complete dental exam; complete elimination of dental and periodontal pathology including crowns on teeth susceptible to fracture, extraction of non-restorable or periodontally uncorrectable teeth; creation of an oral environment that the patient can efficiently maintain in a high state of health; and oral hygiene instruction to maintain excellent oral health.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Anchorage Associates in Radiation Medicine	Anchorage	Alaska	United States	98508
2	Anchorage Radiation Therapy Center	Anchorage	Alaska	United States	99504
3	Alaska Breast Care and Surgery LLC	Anchorage	Alaska	United States	99508
4	Alaska Oncology and Hematology LLC	Anchorage	Alaska	United States	99508
5	Alaska Women's Cancer Care	Anchorage	Alaska	United States	99508
6	Anchorage Oncology Centre	Anchorage	Alaska	United States	99508
7	Katmai Oncology Group	Anchorage	Alaska	United States	99508
8	Providence Alaska Medical Center	Anchorage	Alaska	United States	99508
9	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California	United States	91505
10	University Oncology Associates	Clovis	California	United States	93611
11	Epic Care-Dublin	Dublin	California	United States	94568
12	Bay Area Breast Surgeons Inc	Emeryville	California	United States	94608
13	Epic Care Partners in Cancer Care	Emeryville	California	United States	94608
14	California Cancer Center - Fresno	Fresno	California	United States	93720
15	Scripps Cancer Center	La Jolla	California	United States	92037
16	Contra Costa Regional Medical Center	Martinez	California	United States	94553-3156
17	Alta Bates Summit Medical Center - Summit Campus	Oakland	California	United States	94609
18	Bay Area Tumor Institute	Oakland	California	United States	94609
19	Epic Care Cyberknife Center	Walnut Creek	California	United States	94597
20	Grand Valley Oncology	Grand Junction	Colorado	United States	81501
21	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho	United States	83706
22	Saint Luke's Mountain States Tumor Institute	Boise	Idaho	United States	83712
23	Saint Alphonsus Cancer Care Center-Caldwell	Caldwell	Idaho	United States	83605
24	Kootenai Medical Center	Coeur d'Alene	Idaho	United States	83814
25	Walter Knox Memorial Hospital	Emmett	Idaho	United States	83617
26	Saint Luke's Mountain States Tumor Institute - Fruitland	Fruitland	Idaho	United States	83619
27	Idaho Urologic Institute-Meridian	Meridian	Idaho	United States	83642
28	Saint Luke's Mountain States Tumor Institute - Meridian	Meridian	Idaho	United States	83642
29	Saint Alphonsus Medical Center-Nampa	Nampa	Idaho	United States	83686
30	Saint Luke's Mountain States Tumor Institute - Nampa	Nampa	Idaho	United States	83686
31	Kootenai Cancer Center	Post Falls	Idaho	United States	83854
32	Kootenai Cancer Clinic	Sandpoint	Idaho	United States	83864
33	Saint Luke's Mountain States Tumor Institute-Twin Falls	Twin Falls	Idaho	United States	83301
34	Rush - Copley Medical Center	Aurora	Illinois	United States	60504
35	Saint Joseph Medical Center	Bloomington	Illinois	United States	61701
36	Illinois CancerCare-Bloomington	Bloomington	Illinois	United States	61704
37	Illinois CancerCare-Canton	Canton	Illinois	United States	61520
38	Memorial Hospital of Carbondale	Carbondale	Illinois	United States	62902
39	SIH Cancer Institute	Carterville	Illinois	United States	62918
40	Illinois CancerCare-Carthage	Carthage	Illinois	United States	62321
41	Centralia Oncology Clinic	Centralia	Illinois	United States	62801
42	Rush University Medical Center	Chicago	Illinois	United States	60612
43	Carle on Vermilion	Danville	Illinois	United States	61832
44	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois	United States	62526
45	Decatur Memorial Hospital	Decatur	Illinois	United States	62526
46	Carle Physician Group-Effingham	Effingham	Illinois	United States	62401
47	Crossroads Cancer Center	Effingham	Illinois	United States	62401
48	Illinois CancerCare-Eureka	Eureka	Illinois	United States	61530
49	Illinois CancerCare-Galesburg	Galesburg	Illinois	United States	61401
50	Western Illinois Cancer Treatment Center	Galesburg	Illinois	United States	61401
51	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois	United States	61443
52	Illinois CancerCare-Macomb	Macomb	Illinois	United States	61455
53	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois	United States	61938
54	Good Samaritan Regional Health Center	Mount Vernon	Illinois	United States	62864
55	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois	United States	61350
56	Radiation Oncology of Northern Illinois	Ottawa	Illinois	United States	61350
57	Illinois CancerCare-Pekin	Pekin	Illinois	United States	61554
58	OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center	Pekin	Illinois	United States	61554
59	Illinois CancerCare-Peoria	Peoria	Illinois	United States	61615
60	OSF Saint Francis Radiation Oncology at Peoria Cancer Center	Peoria	Illinois	United States	61615
61	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61636
62	OSF Saint Francis Medical Center	Peoria	Illinois	United States	61637
63	Illinois CancerCare-Peru	Peru	Illinois	United States	61354
64	Valley Radiation Oncology	Peru	Illinois	United States	61354
65	Illinois CancerCare-Princeton	Princeton	Illinois	United States	61356
66	Central Illinois Hematology Oncology Center	Springfield	Illinois	United States	62702
67	Southern Illinois University School of Medicine	Springfield	Illinois	United States	62702
68	Springfield Clinic	Springfield	Illinois	United States	62702
69	Memorial Medical Center	Springfield	Illinois	United States	62781
70	Cancer Care Specialists of Illinois-Swansea	Swansea	Illinois	United States	62226
71	Southwest Illinois Health Services LLP	Swansea	Illinois	United States	62226
72	Carle Cancer Center	Urbana	Illinois	United States	61801
73	The Carle Foundation Hospital	Urbana	Illinois	United States	61801
74	Rush-Copley Healthcare Center	Yorkville	Illinois	United States	60560
75	Deaconess Clinic Downtown	Evansville	Indiana	United States	47713
76	Parkview Hospital Randallia	Fort Wayne	Indiana	United States	46805
77	Indiana University/Melvin and Bren Simon Cancer Center	Indianapolis	Indiana	United States	46202
78	Springmill Medical Center	Indianapolis	Indiana	United States	46290
79	Franciscan Saint Anthony Health-Michigan City	Michigan City	Indiana	United States	46360
80	Woodland Cancer Care Center	Michigan City	Indiana	United States	46360
81	Memorial Regional Cancer Center Day Road	Mishawaka	Indiana	United States	46545
82	Chancellor Center for Oncology	Newburgh	Indiana	United States	47630
83	Reid Health	Richmond	Indiana	United States	47374
84	Memorial Hospital of South Bend	South Bend	Indiana	United States	46601
85	Cancer Center of Kansas - Chanute	Chanute	Kansas	United States	66720
86	Cancer Center of Kansas - Dodge City	Dodge City	Kansas	United States	67801
87	Cancer Center of Kansas - El Dorado	El Dorado	Kansas	United States	67042
88	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas	United States	66701
89	Cancer Center of Kansas-Independence	Independence	Kansas	United States	67301
90	Cancer Center of Kansas-Kingman	Kingman	Kansas	United States	67068
91	Lawrence Memorial Hospital	Lawrence	Kansas	United States	66044
92	Cancer Center of Kansas-Liberal	Liberal	Kansas	United States	67905
93	Cancer Center of Kansas-Manhattan	Manhattan	Kansas	United States	66502
94	Cancer Center of Kansas - McPherson	McPherson	Kansas	United States	67460
95	Cancer Center of Kansas - Newton	Newton	Kansas	United States	67114
96	Cancer Center of Kansas - Parsons	Parsons	Kansas	United States	67357
97	Cancer Center of Kansas - Pratt	Pratt	Kansas	United States	67124
98	Cancer Center of Kansas - Salina	Salina	Kansas	United States	67401
99	Cancer Center of Kansas - Wellington	Wellington	Kansas	United States	67152
100	Associates In Womens Health	Wichita	Kansas	United States	67208
101	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas	United States	67208
102	Cancer Center of Kansas - Wichita	Wichita	Kansas	United States	67214
103	Wesley Medical Center	Wichita	Kansas	United States	67214
104	Cancer Center of Kansas - Winfield	Winfield	Kansas	United States	67156
105	Oncology Hematology Care Inc-Crestview	Crestview Hills	Kentucky	United States	41017
106	Ochsner Medical Center Jefferson	New Orleans	Louisiana	United States	70121
107	Harold Alfond Center for Cancer Care	Augusta	Maine	United States	04330
108	Eastern Maine Medical Center	Bangor	Maine	United States	04401
109	Lafayette Family Cancer Center-EMMC	Brewer	Maine	United States	04412
110	Massachusetts General Hospital Cancer Center	Boston	Massachusetts	United States	02114
111	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
112	Mercy Medical Center	Springfield	Massachusetts	United States	01104
113	Hickman Cancer Center	Adrian	Michigan	United States	49221
114	Saint Joseph Mercy Hospital	Ann Arbor	Michigan	United States	48106
115	Bronson Battle Creek	Battle Creek	Michigan	United States	49017
116	IHA Hematology Oncology Consultants-Brighton	Brighton	Michigan	United States	48114
117	Saint Joseph Mercy Brighton	Brighton	Michigan	United States	48114
118	Henry Ford Cancer Institute?Downriver	Brownstown	Michigan	United States	48183
119	IHA Hematology Oncology Consultants-Canton	Canton	Michigan	United States	48188
120	Saint Joseph Mercy Canton	Canton	Michigan	United States	48188
121	Caro Cancer Center	Caro	Michigan	United States	48723
122	IHA Hematology Oncology Consultants-Chelsea	Chelsea	Michigan	United States	48118
123	Saint Joseph Mercy Chelsea	Chelsea	Michigan	United States	48118
124	Hematology Oncology Consultants-Clarkston	Clarkston	Michigan	United States	48346
125	Newland Medical Associates-Clarkston	Clarkston	Michigan	United States	48346
126	Henry Ford Macomb Hospital-Clinton Township	Clinton Township	Michigan	United States	48038
127	Beaumont Hospital-Dearborn	Dearborn	Michigan	United States	48124
128	Henry Ford Medical Center-Fairlane	Dearborn	Michigan	United States	48126
129	Henry Ford Hospital	Detroit	Michigan	United States	48202
130	Ascension Saint John Hospital	Detroit	Michigan	United States	48236
131	Great Lakes Cancer Management Specialists-Doctors Park	East China Township	Michigan	United States	48054
132	Genesee Cancer and Blood Disease Treatment Center	Flint	Michigan	United States	48503
133	Genesee Hematology Oncology PC	Flint	Michigan	United States	48503
134	Genesys Hurley Cancer Institute	Flint	Michigan	United States	48503
135	Hurley Medical Center	Flint	Michigan	United States	48503
136	Mercy Health Saint Mary's	Grand Rapids	Michigan	United States	49503
137	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan	United States	49503
138	Great Lakes Cancer Management Specialists-Van Elslander Cancer Center	Grosse Pointe Woods	Michigan	United States	48236
139	Lymphoma Clinic of Michigan	Grosse Pointe Woods	Michigan	United States	48236
140	Michigan Breast Specialists-Grosse Pointe Woods	Grosse Pointe Woods	Michigan	United States	48236
141	Allegiance Health	Jackson	Michigan	United States	49201
142	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
143	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007
144	Borgess Medical Center	Kalamazoo	Michigan	United States	49048
145	Sparrow Hospital	Lansing	Michigan	United States	48912
146	Hope Cancer Clinic	Livonia	Michigan	United States	48154
147	Saint Mary Mercy Hospital	Livonia	Michigan	United States	48154
148	Great Lakes Cancer Management Specialists-Macomb Medical Campus	Macomb	Michigan	United States	48044
149	Michigan Breast Specialists-Macomb Township	Macomb	Michigan	United States	48044
150	Saint Mary's Oncology/Hematology Associates of Marlette	Marlette	Michigan	United States	48453
151	Toledo Clinic Cancer Centers-Monroe	Monroe	Michigan	United States	48162
152	Mercy Health Mercy Campus	Muskegon	Michigan	United States	49444
153	Lakeland Hospital Niles	Niles	Michigan	United States	49120
154	Ascension Providence Hospitals - Novi	Novi	Michigan	United States	48374
155	Henry Ford Medical Center-Columbus	Novi	Michigan	United States	48377
156	21st Century Oncology-Pontiac	Pontiac	Michigan	United States	48341
157	Hope Cancer Center	Pontiac	Michigan	United States	48341
158	Newland Medical Associates-Pontiac	Pontiac	Michigan	United States	48341
159	Saint Joseph Mercy Oakland	Pontiac	Michigan	United States	48341
160	Spectrum Health Reed City Hospital	Reed City	Michigan	United States	49677
161	Great Lakes Cancer Management Specialists-Rochester Hills	Rochester Hills	Michigan	United States	48309
162	Saint Mary's of Michigan	Saginaw	Michigan	United States	48601
163	Oncology Hematology Associates of Saginaw Valley PC	Saginaw	Michigan	United States	48604
164	Lakeland Medical Center Saint Joseph	Saint Joseph	Michigan	United States	49085
165	Marie Yeager Cancer Center	Saint Joseph	Michigan	United States	49085
166	Ascension Providence Hospitals - Southfield	Southfield	Michigan	United States	48075
167	Bhadresh Nayak MD PC-Sterling Heights	Sterling Heights	Michigan	United States	48312
168	Saint Joseph Health System-Tawas City	Tawas City	Michigan	United States	48764
169	Munson Medical Center	Traverse City	Michigan	United States	49684
170	Advanced Breast Care Center PLLC	Warren	Michigan	United States	48088
171	Bhadresh Nayak MD PC-Warren	Warren	Michigan	United States	48093
172	Great Lakes Cancer Management Specialists-Macomb Professional Building	Warren	Michigan	United States	48093
173	Macomb Hematology Oncology PC	Warren	Michigan	United States	48093
174	Michigan Breast Specialists-Warren	Warren	Michigan	United States	48093
175	Saint John Macomb-Oakland Hospital	Warren	Michigan	United States	48093
176	Henry Ford West Bloomfield Hospital	West Bloomfield	Michigan	United States	48322
177	Saint Mary's Oncology/Hematology Associates of West Branch	West Branch	Michigan	United States	48661
178	Metro Health Hospital	Wyoming	Michigan	United States	49519
179	Huron Gastroenterology PC	Ypsilanti	Michigan	United States	48106
180	IHA Hematology Oncology Consultants-Ann Arbor	Ypsilanti	Michigan	United States	48197
181	Sanford Joe Lueken Cancer Center	Bemidji	Minnesota	United States	56601
182	Essentia Health Saint Joseph's Medical Center	Brainerd	Minnesota	United States	56401
183	Essentia Health - Deer River Clinic	Deer River	Minnesota	United States	56636
184	Essentia Health Saint Mary's - Detroit Lakes Clinic	Detroit Lakes	Minnesota	United States	56501
185	Essentia Health Cancer Center	Duluth	Minnesota	United States	55805
186	Essentia Health Saint Mary's Medical Center	Duluth	Minnesota	United States	55805
187	Miller-Dwan Hospital	Duluth	Minnesota	United States	55805
188	Lake Region Healthcare Corporation-Cancer Care	Fergus Falls	Minnesota	United States	56537
189	Essentia Health - Fosston	Fosston	Minnesota	United States	56542
190	Essentia Health Hibbing Clinic	Hibbing	Minnesota	United States	55746
191	Essentia Health - Park Rapids	Park Rapids	Minnesota	United States	56470
192	Mayo Clinic	Rochester	Minnesota	United States	55905
193	Essentia Health Sandstone	Sandstone	Minnesota	United States	55072
194	Sanford Thief River Falls Medical Center	Thief River Falls	Minnesota	United States	56701
195	Essentia Health Virginia Clinic	Virginia	Minnesota	United States	55792
196	Sanford Cancer Center Worthington	Worthington	Minnesota	United States	56187
197	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
198	Saint Louis Cancer and Breast Institute-Ballwin	Ballwin	Missouri	United States	63011
199	Central Care Cancer Center - Bolivar	Bolivar	Missouri	United States	65613
200	Parkland Health Center-Bonne Terre	Bonne Terre	Missouri	United States	63628
201	Cox Cancer Center Branson	Branson	Missouri	United States	65616
202	Saint Francis Medical Center	Cape Girardeau	Missouri	United States	63703
203	Southeast Cancer Center	Cape Girardeau	Missouri	United States	63703
204	Capital Region Southwest Campus	Jefferson City	Missouri	United States	65109
205	Freeman Health System	Joplin	Missouri	United States	64804
206	Mercy Hospital Joplin	Joplin	Missouri	United States	64804
207	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri	United States	65401
208	Mercy Clinic-Rolla-Cancer and Hematology	Rolla	Missouri	United States	65401
209	Heartland Regional Medical Center	Saint Joseph	Missouri	United States	64507
210	Saint Louis Cancer and Breast Institute-South City	Saint Louis	Missouri	United States	63109
211	Missouri Baptist Medical Center	Saint Louis	Missouri	United States	63131
212	Mercy Hospital Saint Louis	Saint Louis	Missouri	United States	63141
213	Sainte Genevieve County Memorial Hospital	Sainte Genevieve	Missouri	United States	63670
214	Mercy Hospital Springfield	Springfield	Missouri	United States	65804
215	CoxHealth South Hospital	Springfield	Missouri	United States	65807
216	Missouri Baptist Sullivan Hospital	Sullivan	Missouri	United States	63080
217	Missouri Baptist Outpatient Center-Sunset Hills	Sunset Hills	Missouri	United States	63127
218	Mercy Hospital Washington	Washington	Missouri	United States	63090
219	Community Hospital of Anaconda	Anaconda	Montana	United States	59711
220	Billings Clinic Cancer Center	Billings	Montana	United States	59101
221	Saint Vincent Healthcare	Billings	Montana	United States	59101
222	Bozeman Deaconess Hospital	Bozeman	Montana	United States	59715
223	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana	United States	59701
224	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana	United States	59405
225	Great Falls Clinic	Great Falls	Montana	United States	59405
226	Saint Peter's Community Hospital	Helena	Montana	United States	59601
227	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
228	Saint Patrick Hospital - Community Hospital	Missoula	Montana	United States	59802
229	Community Medical Hospital	Missoula	Montana	United States	59804
230	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
231	Norris Cotton Cancer Center-Nashua	Nashua	New Hampshire	United States	03063
232	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
233	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
234	Sanford Bismarck Medical Center	Bismarck	North Dakota	United States	58501
235	Essentia Health Cancer Center-South University Clinic	Fargo	North Dakota	United States	58103
236	Sanford South University Medical Center	Fargo	North Dakota	United States	58103
237	Roger Maris Cancer Center	Fargo	North Dakota	United States	58122
238	Sanford Broadway Medical Center	Fargo	North Dakota	United States	58122
239	Essentia Health - Jamestown Clinic	Jamestown	North Dakota	United States	58401
240	Indu and Raj Soin Medical Center	Beavercreek	Ohio	United States	45431
241	Strecker Cancer Center-Belpre	Belpre	Ohio	United States	45714
242	Dayton Physicians LLC-Miami Valley South	Centerville	Ohio	United States	45459
243	Miami Valley Hospital South	Centerville	Ohio	United States	45459
244	Adena Regional Medical Center	Chillicothe	Ohio	United States	45601
245	Oncology Hematology Care Inc-Eden Park	Cincinnati	Ohio	United States	45202
246	Oncology Hematology Care Inc-Mercy West	Cincinnati	Ohio	United States	45211
247	Oncology Hematology Care Inc - Anderson	Cincinnati	Ohio	United States	45230
248	Oncology Hematology Care Inc-Kenwood	Cincinnati	Ohio	United States	45236
249	Oncology Hematology Care Inc-Blue Ash	Cincinnati	Ohio	United States	45242
250	Mount Carmel East Hospital	Columbus	Ohio	United States	43213
251	Columbus Oncology and Hematology Associates Inc	Columbus	Ohio	United States	43214
252	Riverside Methodist Hospital	Columbus	Ohio	United States	43214
253	Grant Medical Center	Columbus	Ohio	United States	43215
254	The Mark H Zangmeister Center	Columbus	Ohio	United States	43219
255	Mount Carmel Health Center West	Columbus	Ohio	United States	43222
256	Doctors Hospital	Columbus	Ohio	United States	43228
257	Good Samaritan Hospital - Dayton	Dayton	Ohio	United States	45406
258	Miami Valley Hospital	Dayton	Ohio	United States	45409
259	Dayton Physicians LLC-Samaritan North	Dayton	Ohio	United States	45415
260	Miami Valley Hospital North	Dayton	Ohio	United States	45415
261	Delaware Health Center-Grady Cancer Center	Delaware	Ohio	United States	43015
262	Delaware Radiation Oncology	Delaware	Ohio	United States	43015
263	Grady Memorial Hospital	Delaware	Ohio	United States	43015
264	Oncology Hematology Care Inc-Healthplex	Fairfield	Ohio	United States	45014
265	Armes Family Cancer Center	Findlay	Ohio	United States	45840
266	Blanchard Valley Hospital	Findlay	Ohio	United States	45840
267	Orion Cancer Care	Findlay	Ohio	United States	45840
268	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio	United States	45005-1066
269	Dayton Physicians LLC-Atrium	Franklin	Ohio	United States	45005
270	Dayton Physicians LLC-Wayne	Greenville	Ohio	United States	45331
271	Wayne Hospital	Greenville	Ohio	United States	45331
272	Greater Dayton Cancer Center	Kettering	Ohio	United States	45409
273	First Dayton Cancer Care	Kettering	Ohio	United States	45420
274	Kettering Medical Center	Kettering	Ohio	United States	45429
275	Fairfield Medical Center	Lancaster	Ohio	United States	43130
276	OhioHealth Mansfield Hospital	Mansfield	Ohio	United States	44903
277	Marietta Memorial Hospital	Marietta	Ohio	United States	45750
278	OhioHealth Marion General Hospital	Marion	Ohio	United States	43302
279	Toledo Clinic Cancer Centers-Maumee	Maumee	Ohio	United States	43537
280	Toledo Radiation Oncology at Northwest Ohio Onocolgy Center	Maumee	Ohio	United States	43537
281	Dayton Physicians LLC-Signal Point	Middletown	Ohio	United States	45042
282	Knox Community Hospital	Mount Vernon	Ohio	United States	43050
283	Licking Memorial Hospital	Newark	Ohio	United States	43055
284	Newark Radiation Oncology	Newark	Ohio	United States	43055
285	Saint Charles Hospital	Oregon	Ohio	United States	43616
286	Mercy Health Perrysburg Cancer Center	Perrysburg	Ohio	United States	43551
287	Southern Ohio Medical Center	Portsmouth	Ohio	United States	45662
288	Dayton Physicians LLC-Wilson	Sidney	Ohio	United States	45365
289	Springfield Regional Cancer Center	Springfield	Ohio	United States	45504
290	Springfield Regional Medical Center	Springfield	Ohio	United States	45505
291	Mercy Saint Anne Hospital	Toledo	Ohio	United States	43623
292	Toledo Clinic Cancer Centers-Toledo	Toledo	Ohio	United States	43623
293	Dayton Physicians LLC-Upper Valley	Troy	Ohio	United States	45373
294	Upper Valley Medical Center	Troy	Ohio	United States	45373
295	Saint Ann's Hospital	Westerville	Ohio	United States	43081
296	Genesis Healthcare System Cancer Care Center	Zanesville	Ohio	United States	43701
297	Cancer Centers of Southwest Oklahoma Research	Lawton	Oklahoma	United States	73505
298	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
299	Mercy Hospital Oklahoma City	Oklahoma City	Oklahoma	United States	73120
300	Saint Alphonsus Medical Center-Baker City	Baker City	Oregon	United States	97814
301	Saint Charles Health System	Bend	Oregon	United States	97701
302	Clackamas Radiation Oncology Center	Clackamas	Oregon	United States	97015
303	Providence Oncology and Hematology Care Southeast	Clackamas	Oregon	United States	97015
304	Bay Area Hospital	Coos Bay	Oregon	United States	97420
305	Providence Newberg Medical Center	Newberg	Oregon	United States	97132
306	Saint Alphonsus Medical Center-Ontario	Ontario	Oregon	United States	97914
307	Providence Willamette Falls Medical Center	Oregon City	Oregon	United States	97045
308	Providence Portland Medical Center	Portland	Oregon	United States	97213
309	Providence Saint Vincent Medical Center	Portland	Oregon	United States	97225
310	Saint Charles Health System-Redmond	Redmond	Oregon	United States	97756
311	Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania	United States	18103
312	Lehigh Valley Hospital - Muhlenberg	Bethlehem	Pennsylvania	United States	18017
313	Geisinger Medical Center	Danville	Pennsylvania	United States	17822
314	Geisinger Medical Center-Cancer Center Hazleton	Hazleton	Pennsylvania	United States	18201
315	Geisinger Medical Oncology-Lewisburg	Lewisburg	Pennsylvania	United States	17837
316	Lewistown Hospital	Lewistown	Pennsylvania	United States	17044
317	Geisinger Cancer Services-Pottsville	Pottsville	Pennsylvania	United States	17901
318	Community Medical Center	Scranton	Pennsylvania	United States	18510
319	Geisinger Medical Oncology-Selinsgrove	Selinsgrove	Pennsylvania	United States	17870
320	Geisinger Medical Group	State College	Pennsylvania	United States	16801
321	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania	United States	18711
322	Gibbs Cancer Center-Gaffney	Gaffney	South Carolina	United States	29341
323	Saint Francis Hospital	Greenville	South Carolina	United States	29601
324	Saint Francis Cancer Center	Greenville	South Carolina	United States	29607
325	Gibbs Cancer Center-Pelham	Greer	South Carolina	United States	29651
326	Spartanburg Medical Center	Spartanburg	South Carolina	United States	29303
327	MGC Hematology Oncology-Union	Union	South Carolina	United States	29379
328	Sanford Cancer Center Oncology Clinic	Sioux Falls	South Dakota	United States	57104
329	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota	United States	57117-5134
330	Parkland Memorial Hospital	Dallas	Texas	United States	75235
331	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas	United States	75390
332	UT Southwestern/Simmons Cancer Center-Fort Worth	Fort Worth	Texas	United States	76104
333	M D Anderson Cancer Center	Houston	Texas	United States	77030
334	Farmington Health Center	Farmington	Utah	United States	84025
335	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah	United States	84112
336	South Jordan Health Center	South Jordan	Utah	United States	84009
337	Norris Cotton Cancer Center-North	Saint Johnsbury	Vermont	United States	05819
338	Danville Hematology Oncology	Danville	Virginia	United States	24541
339	Danville Regional Medical Center	Danville	Virginia	United States	24541
340	Providence Regional Cancer System-Aberdeen	Aberdeen	Washington	United States	98520
341	Cancer Care Center at Island Hospital	Anacortes	Washington	United States	98221
342	Swedish Cancer Institute-Eastside Oncology Hematology	Bellevue	Washington	United States	98005
343	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington	United States	98225
344	Providence Regional Cancer System-Centralia	Centralia	Washington	United States	98531
345	Swedish Medical Center-Edmonds	Edmonds	Washington	United States	98026
346	Providence Regional Cancer Partnership	Everett	Washington	United States	98201
347	Swedish Cancer Institute-Issaquah	Issaquah	Washington	United States	98029
348	Kadlec Clinic Hematology and Oncology	Kennewick	Washington	United States	99336
349	Providence Regional Cancer System-Lacey	Lacey	Washington	United States	98503
350	PeaceHealth Saint John Medical Center	Longview	Washington	United States	98632
351	Minor and James Medical PLLC	Seattle	Washington	United States	98104
352	Pacific Gynecology Specialists	Seattle	Washington	United States	98104
353	Swedish Medical Center-Ballard Campus	Seattle	Washington	United States	98107
354	Kaiser Permanente Washington	Seattle	Washington	United States	98112
355	Swedish Medical Center-First Hill	Seattle	Washington	United States	98122-4307
356	Swedish Medical Center-Cherry Hill	Seattle	Washington	United States	98122-5711
357	PeaceHealth United General Medical Center	Sedro-Woolley	Washington	United States	98284
358	Providence Regional Cancer System-Shelton	Shelton	Washington	United States	98584
359	Rockwood Clinic Cancer Treatment Center-Valley	Spokane Valley	Washington	United States	99216
360	Rockwood Cancer Treatment Center-DHEC-Downtown	Spokane	Washington	United States	99204
361	Rockwood North Cancer Treatment Center	Spokane	Washington	United States	99218
362	PeaceHealth Southwest Medical Center	Vancouver	Washington	United States	98664
363	Providence Saint Mary Regional Cancer Center	Walla Walla	Washington	United States	99362
364	North Star Lodge Cancer Center at Yakima Valley Memorial Hospital	Yakima	Washington	United States	98902
365	Providence Regional Cancer System-Yelm	Yelm	Washington	United States	98597
366	Ashland Memorial Medical Center	Ashland	Wisconsin	United States	54806
367	Duluth Clinic Ashland	Ashland	Wisconsin	United States	54806
368	Aurora Cancer Care-Southern Lakes VLCC	Burlington	Wisconsin	United States	53105
369	Aurora Health Center-Fond du Lac	Fond Du Lac	Wisconsin	United States	54937
370	Aurora Health Care Germantown Health Center	Germantown	Wisconsin	United States	53022
371	Aurora Cancer Care-Grafton	Grafton	Wisconsin	United States	53024
372	Aurora BayCare Medical Center	Green Bay	Wisconsin	United States	54311
373	Aurora Cancer Care-Kenosha South	Kenosha	Wisconsin	United States	53142
374	Gundersen Lutheran Medical Center	La Crosse	Wisconsin	United States	54601
375	Aurora Bay Area Medical Group-Marinette	Marinette	Wisconsin	United States	54143
376	Aurora Cancer Care-Milwaukee	Milwaukee	Wisconsin	United States	53209
377	Aurora Saint Luke's Medical Center	Milwaukee	Wisconsin	United States	53215
378	Aurora Sinai Medical Center	Milwaukee	Wisconsin	United States	53233
379	Vince Lombardi Cancer Clinic - Oshkosh	Oshkosh	Wisconsin	United States	54904
380	Aurora Cancer Care-Racine	Racine	Wisconsin	United States	53406
381	Vince Lombardi Cancer Clinic-Sheboygan	Sheboygan	Wisconsin	United States	53081
382	Aurora Medical Center in Summit	Summit	Wisconsin	United States	53066
383	Vince Lombardi Cancer Clinic-Two Rivers	Two Rivers	Wisconsin	United States	54241
384	Aurora Cancer Care-Milwaukee West	Wauwatosa	Wisconsin	United States	53226
385	Aurora West Allis Medical Center	West Allis	Wisconsin	United States	53227
386	Big Horn Basin Cancer Center	Cody	Wyoming	United States	82414
387	Billings Clinic-Cody	Cody	Wyoming	United States	82414
388	Welch Cancer Center	Sheridan	Wyoming	United States	82801