Rituximab in Treating Patients With Low Tumor Burden Indolent Non-Hodgkin's Lymphoma

• Sponsor: Eastern Cooperative Oncology Group (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT00075946
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 545
• Locations: 483
• Arms: 2
• Anticipated Duration (Months): 238
• Patients Per Site: 1.1
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. It is not yet known which rituximab regimen is more effective in treating indolent non-Hodgkin's lymphoma.

PURPOSE: This randomized phase III trial is studying two different schedules of rituximab and comparing them to see how well they work in treating patients with low tumor burden indolent stage III non-Hodgkin's lymphoma or stage IV non-Hodgkin's lymphoma.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Biological: rituximab	Phase 3

Detailed Description

OBJECTIVES:

Primary

• To compare time to rituximab failure between the rituximab scheduled and rituximab retreatment arms.

Secondary

• To compare the time to first cytotoxic therapy between the rituximab scheduled and rituximab retreatment arms.

• To document the rationale for beginning cytotoxic therapy; defined as chemotherapy, radiation therapy or radioimmunotherapy.

• To compare the toxicities associated with rituximab therapy between the two randomized treatment arms.

• Quality of Life Objectives:

1. To compare health-related quality of life, distress, psychological functioning, physical well-being and functional well-being of patients receiving rituximab scheduled to those receiving rituximab retreatment.

2. To examine the impact of differential treatment response (delayed time to rituximab failure and/or time to first cytotoxic therapy), if observed, on quality of life, distress, and psychological functioning on patients receiving rituximab scheduled to those receiving rituximab retreatment.

3. To obtain prospective data on physical and functional well-being during treatment with rituximab.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to histologic subtype (follicular vs other), age (under 60 vs 60 and over), and the time from diagnosis (less than 1 year vs at least 1 year).

• Induction rituximab: Patients receive rituximab Intravenous (IV) once a week for 4 weeks.

Patients are re-evaluated 9 weeks after the completion of induction rituximab. Patients with a partial or complete response to induction rituximab are randomized to 1 of 2 treatment arms.

• Arm A (retreatment rituximab): Patients receive rituximab IV once a week for 4 weeks upon disease progression provided time to progression is more than 6 months.

• Arm B (scheduled rituximab): Patients receive a single dose of rituximab IV once every 13 weeks until disease progression and in the absence of unacceptable toxicity.

Quality of life is assessed after induction rituximab treatment and at 26, 39, 65, 117, 169, and 221 weeks after randomization.

Patients are followed at least annually for 15 years from study entry.

Study Design

• Study Type: Interventional
• Actual Enrollment: 545 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomized Phase III Trial Comparing Two Different Rituximab Dosing Regimens For Patients With Low Tumor Burden Indolent Non-Hodgkin's Lymphoma
• Actual Study Start Date: Nov 1, 2003
• Actual Primary Completion Date: Sep 1, 2013
• Anticipated Study Completion Date: Sep 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm A: Rituximab Retreatment Patients receive rituximab IV once a week for 4 weeks upon disease progression provided time to progression is more than 6 months.	Biological: rituximab; Given IV
Experimental: Arm B: Rituximab Scheduled Patients receive a single dose of rituximab IV once every 13 weeks until disease progression and in the absence of unacceptable toxicity.	Biological: rituximab; Given IV

Outcome Measures

Primary Outcome Measures

1. Time to Rituximab Failure (TTRF) [Assessed (by restaging CT scans) 26 weeks ± 2 weeks from each rituximab treatment (including induction), counting the first rituximab dose as Day 1, until rituximab failure observed or July 17, 2013, whichever occurred first.]

   TTRF is defined as the time from randomization until any one of the following criteria are met, and censored at last disease assessment for cases who have not experienced failure (with the cut-off date for final analysis of 11/1/2011): 1. No response (partial response (PR) or complete response (CR)) to rituximab retreatment (Arm A treatment). 2. Time to progression < 26 weeks from day 1 of most recent rituximab treatment. 3. Initiation of alternative therapy. 4. Inability to complete protocol therapy (due to adverse events, patient preference, or any other reason, including death).

Secondary Outcome Measures

1. Time to First Cytotoxic Therapy (TTFC) [Assessed every 13 weeks until rituximab failure observed or August 2013, whichever occurred first.]

   TTFC is defined as the time from randomization to the time of first cytotoxic therapy (chemo and radio therapy), and censored as last follow-up time if no cytotoxic therapy has been used. Since median TTFC was not reached in 3 out of the 4 groups, 3-year TTFC was reported which was defined as the probability of not starting first cytotoxic therapy at 3 years.

2. Overall Health-related Quality of Life (HRQL) at 6 Month After Randomization [Assessed at baseline and 6 months after randomization.]

   The overall HRQL was measured by the change in Functional Assessment of Cancer Therapy - General (FACT-G) from baseline to 6 months after randomization. The FACT-G is a 27-item assessment used to measure HRQL, specifically, physical, functional, social and emotional well-being. The total score ranges from 0 to 108, with higher scores indicating better HRQL.

Eligibility Criteria

Criteria

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

INCLUSION CRITERIA:

• Histologically confirmed non-Hodgkin's lymphoma, including 1 of the following:

• Follicular grade 1 or 2

• Small lymphocytic

• Marginal zone (nodal)

• Marginal zone (splenic)

• Mucosa-associated lymphoid tissue (MALT)

• Stage III or IV disease

• Must meet the following criteria for low tumor burden:

• No nodal or extranodal mass at least 7 cm

• Less than 3 nodal masses greater than 3 cm in diameter

• No systemic symptoms or B symptoms

• No splenomegaly greater than 16 cm by a computed tomography (CT) scan

• No evidence of risk of compression of a vital organ (i.e., ureteral or epidural)

• No leukemic phase with greater than 5,000/mm^3 circulating lymphocytes

• No cytopenias, defined as any of the following:

• Platelet count less than 100,000/mm^3

• Hemoglobin less than 10 g/dL

• Absolute neutrophil count less than 1,500/mm^3

• At least 1 objective measurable disease parameter

• Abnormal positron emission tomography (PET) scans will not constitute evaluable disease unless verified by CT scan or other appropriate imaging

• Age: 18 and over

• Eastern Cooperative Oncology Group (ECOG) performance status 0-1

• Must meet the following criteria for labs:

• Hematopoietic

• Absolute neutrophil count at least 1,500/mm^3*

• Hemoglobin at least 10 g/dL*

• Platelet count at least 100,000/mm^3*

• NOTE: *Without growth factor and/or transfusion support

• Hepatic

• Bilirubin no greater than 2 times upper limit of normal (ULN) OR direct bilirubin normal for patients with Gilbert's Syndrome

• The aspartate transaminase (AST) and alanine transaminase (ALT) ratio (AST/ALT) no greater than 5 times ULN

• Hepatitis B surface antigen negative

• Renal

• Creatinine no greater than 2 times ULN

EXCLUSION CRITERIA:

• Evidence of transformation to a large cell histology

• Pregnant or nursing. Fertile patients must use effective contraception

• HIV positive

• Uncontrolled active infection

• Other malignancy within the past 2 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix

• Prior immunotherapy for lymphoma

• Prior chemotherapy for lymphoma

• Concurrent chemotherapy

• Prior radiotherapy for lymphoma

• Concurrent radiotherapy

• Concurrent radioimmunotherapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic Scottsdale	Scottsdale	Arizona	United States	85259-5499
2	Hembree Mercy Cancer Center at St. Edward Mercy Medical Center	Fort Smith	Arkansas	United States	72903
3	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
4	Providence Saint Joseph Medical Center - Burbank	Burbank	California	United States	91505
5	North Bay Cancer Center	Fairfield	California	United States	94533
6	Kaiser Permanente - Fremont	Fremont	California	United States	94538
7	Kaiser Permanente Medical Center - Hayward	Hayward	California	United States	94545
8	Memorial Medical Center	Modesto	California	United States	95355
9	Kaiser Permanente Medical Center - Oakland	Oakland	California	United States	94611
10	Desert Regional Medical Center Comprehensive Cancer Center	Palm Springs	California	United States	92262
11	Veterans Affairs Medical Center - Palo Alto	Palo Alto	California	United States	94304
12	Kaiser Permanente Medical Center - Redwood City	Redwood City	California	United States	94063
13	Kaiser Permanente Medical Center - Richmond	Richmond	California	United States	94801
14	Kaiser Permanente Medical Center - Roseville	Roseville	California	United States	95661
15	South Sacramento Kaiser-Permanente Medical Center	Sacramento	California	United States	95823
16	Kaiser Permanente Medical Center - Sacramento	Sacramento	California	United States	95825
17	Kaiser Permanente Medical Office -Vandever Medical Office	San Diego	California	United States	92120
18	Kaiser Permanente Medical Center - San Francisco Geary Campus	San Francisco	California	United States	94115
19	Kaiser Permanente Medical Center - Santa Teresa	San Jose	California	United States	95119
20	Kaiser Foundation Hospital - San Rafael	San Rafael	California	United States	94903
21	Kaiser Permanente Medical Center - Santa Clara Kiely Campus	Santa Clara	California	United States	95051
22	Kaiser Permanente Medical Center - Santa Rosa	Santa Rosa	California	United States	95403
23	Kaiser Permanente Medical Center - South San Francisco	South San Francisco	California	United States	94080
24	Stanford Cancer Center	Stanford	California	United States	94305-5824
25	Kaiser Permanente Medical Facility - Stockton	Stockton	California	United States	95210
26	Camino Medical Group - Treatment Center	Sunnyvale	California	United States	94088
27	Kaiser Permanente Medical Center - Vallejo	Vallejo	California	United States	94589
28	Kaiser Permanente Medical Center - Walnut Creek	Walnut Creek	California	United States	94596
29	Aurora Presbyterian Hospital	Aurora	Colorado	United States	80012
30	Boulder Community Hospital	Boulder	Colorado	United States	80301-9019
31	Penrose Cancer Center at Penrose Hospital	Colorado Springs	Colorado	United States	80933
32	St. Anthony Central Hospital	Denver	Colorado	United States	80204
33	Porter Adventist Hospital	Denver	Colorado	United States	80210
34	Presbyterian - St. Luke's Medical Center	Denver	Colorado	United States	80218
35	St. Joseph Hospital	Denver	Colorado	United States	80218
36	Rose Medical Center	Denver	Colorado	United States	80220
37	CCOP - Colorado Cancer Research Program	Denver	Colorado	United States	80224-2522
38	Swedish Medical Center	Englewood	Colorado	United States	80110
39	Poudre Valley Hospital	Fort Collins	Colorado	United States	80524
40	Front Range Cancer Specialists	Fort Collins	Colorado	United States	80528
41	St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center	Grand Junction	Colorado	United States	81502
42	North Colorado Medical Center	Greeley	Colorado	United States	80631
43	Sky Ridge Medical Center	Lone Tree	Colorado	United States	80124
44	Hope Cancer Care Center at Longmont United Hospital	Longmont	Colorado	United States	80502
45	McKee Medical Center	Loveland	Colorado	United States	80539
46	St. Mary - Corwin Regional Medical Center	Pueblo	Colorado	United States	81004
47	North Suburban Medical Center	Thornton	Colorado	United States	80229
48	Exempla Lutheran Medical Center	Wheat Ridge	Colorado	United States	80033
49	Eastern Connecticut Hematology and Oncology Associates	Norwich	Connecticut	United States	06360
50	Tunnell Cancer Center at Beebe Medical Center	Lewes	Delaware	United States	19958
51	CCOP - Christiana Care Health Services	Newark	Delaware	United States	19713
52	Walter Reed Army Medical Center	Washington	District of Columbia	United States	20307-5001
53	Eugene M. and Christine E. Lynn Cancer Institute at Boca Raton Community Hospital - Main Campus	Boca Raton	Florida	United States	33486
54	Michael and Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital	Fort Lauderdale	Florida	United States	33308
55	University of Florida Shands Cancer Center	Gainesville	Florida	United States	32610-0232
56	Memorial Cancer Institute at Memorial Regional Hospital	Hollywood	Florida	United States	33021
57	Baptist Cancer Institute - Jacksonville	Jacksonville	Florida	United States	32207
58	Mayo Clinic - Jacksonville	Jacksonville	Florida	United States	32224
59	Ella Milbank Foshay Cancer Center at Jupiter Medical Center	Jupiter	Florida	United States	33458
60	CCOP - Mount Sinai Medical Center	Miami Beach	Florida	United States	33140
61	Augusta Oncology Associates - Walton Way	Augusta	Georgia	United States	30901
62	Northeast Georgia Medical Center	Gainesville	Georgia	United States	30501
63	Medical Center of Central Georgia	Macon	Georgia	United States	31208
64	Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/Candler	Savannah	Georgia	United States	31405
65	Mountain States Tumor Institute at St. Luke's Regional Medical Center	Boise	Idaho	United States	83712
66	Saint Anthony's Hospital at Saint Anthony's Health Center	Alton	Illinois	United States	62002
67	Rush-Copley Cancer Care Center	Aurora	Illinois	United States	60504
68	St. Joseph Medical Center	Bloomington	Illinois	United States	61701
69	Graham Hospital	Canton	Illinois	United States	61520
70	Memorial Hospital	Carthage	Illinois	United States	62321
71	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois	United States	60611-3013
72	John H. Stroger, Jr. Hospital of Cook County	Chicago	Illinois	United States	60612-3785
73	Resurrection Medical Center	Chicago	Illinois	United States	60631
74	Louis A. Weiss Memorial Hospital	Chicago	Illinois	United States	60640
75	Creticos Cancer Center at Advocate Illinois Masonic Medical Center	Chicago	Illinois	United States	60657
76	Decatur Memorial Hospital Cancer Care Institute	Decatur	Illinois	United States	62526
77	Elmhurst Memorial Hospital	Elmhurst	Illinois	United States	60126
78	Eureka Community Hospital	Eureka	Illinois	United States	61530
79	Evanston Northwestern Healthcare - Evanston Hospital	Evanston	Illinois	United States	60201-1781
80	St. Francis Hospital	Evanston	Illinois	United States	60202
81	Galesburg Clinic, PC	Galesburg	Illinois	United States	61401
82	Galesburg Cottage Hospital	Galesburg	Illinois	United States	61401
83	Delnor Community Hospital - Geneva	Geneva	Illinois	United States	60134
84	Ingalls Cancer Care Center at Ingalls Memorial Hospital	Harvey	Illinois	United States	60426
85	Mason District Hospital	Havana	Illinois	United States	62644
86	Hinsdale Hematology Oncology Associates	Hinsdale	Illinois	United States	60521
87	Hopedale Medical Complex	Hopedale	Illinois	United States	61747
88	Joliet Oncology-Hematology Associates, Limited - West	Joliet	Illinois	United States	60435
89	Provena St. Mary's Regional Cancer Center - Kankakee	Kankakee	Illinois	United States	60901
90	La Grange Memorial Hospital	La Grange	Illinois	United States	60525
91	McDonough District Hospital	Macomb	Illinois	United States	61455
92	Good Samaritan Regional Health Center	Mount Vernon	Illinois	United States	62864
93	Hematology Oncology Consultants - Naperville	Naperville	Illinois	United States	60540
94	BroMenn Regional Medical Center	Normal	Illinois	United States	61761
95	Community Cancer Center	Normal	Illinois	United States	61761
96	Saint James Hospital and Health Centers Comprehensive Cancer Institute - Olympia Fields	Olympia Fields	Illinois	United States	60461
97	Community Hospital of Ottawa	Ottawa	Illinois	United States	61350
98	Oncology Hematology Associates of Central Illinois, PC - Ottawa	Ottawa	Illinois	United States	61350
99	Cancer Treatment Center at Pekin Hospital	Pekin	Illinois	United States	61554
100	Proctor Hospital	Peoria	Illinois	United States	61614
101	CCOP - Illinois Oncology Research Association	Peoria	Illinois	United States	61615
102	Oncology Hematology Associates of Central Illinois, PC - Peoria	Peoria	Illinois	United States	61615
103	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61636
104	OSF St. Francis Medical Center	Peoria	Illinois	United States	61637
105	Illinois Valley Community Hospital	Peru	Illinois	United States	61354
106	Perry Memorial Hospital	Princeton	Illinois	United States	61356
107	Swedish-American Regional Cancer Center	Rockford	Illinois	United States	61104-2315
108	St. Margaret's Hospital	Spring Valley	Illinois	United States	61362
109	Regional Cancer Center at Memorial Medical Center	Springfield	Illinois	United States	62781-0001
110	Carle Cancer Center at Carle Foundation Hospital	Urbana	Illinois	United States	61801
111	CCOP - Carle Cancer Center	Urbana	Illinois	United States	61801
112	St. Francis Hospital and Health Centers - Beech Grove Campus	Beech Grove	Indiana	United States	46107
113	Elkhart General Hospital	Elkhart	Indiana	United States	46515
114	Fort Wayne Medical Oncology and Hematology	Fort Wayne	Indiana	United States	46815
115	Center for Cancer Care at Goshen General Hospital	Goshen	Indiana	United States	46526
116	Indiana University Melvin and Bren Simon Cancer Center	Indianapolis	Indiana	United States	46202-5289
117	Veterans Affairs Medical Center - Indianapolis	Indianapolis	Indiana	United States	46202
118	William N. Wishard Memorial Hospital	Indianapolis	Indiana	United States	46202
119	Howard Community Hospital	Kokomo	Indiana	United States	46904
120	Center for Cancer Therapy at LaPorte Hospital and Health Services	La Porte	Indiana	United States	46350
121	Clarian Arnett Cancer Care	Lafayette	Indiana	United States	47904
122	Saint Anthony Memorial Health Centers	Michigan City	Indiana	United States	46360
123	Reid Hospital & Health Care Services	Richmond	Indiana	United States	47374
124	CCOP - Northern Indiana CR Consortium	South Bend	Indiana	United States	46601
125	Memorial Hospital of South Bend	South Bend	Indiana	United States	46601
126	Saint Joseph Regional Medical Center	South Bend	Indiana	United States	46617
127	McFarland Clinic, PC	Ames	Iowa	United States	50010
128	Hematology Oncology Associates of the Quad Cities	Bettendorf	Iowa	United States	52722
129	Cedar Rapids Oncology Associates	Cedar Rapids	Iowa	United States	52403
130	Genesis Regional Cancer Center at Genesis Medical Center	Davenport	Iowa	United States	52803
131	Genesis Medical Center - West Campus	Davenport	Iowa	United States	52804
132	Mercy Capitol Hospital	Des Moines	Iowa	United States	50307
133	CCOP - Iowa Oncology Research Association	Des Moines	Iowa	United States	50309
134	John Stoddard Cancer Center at Iowa Methodist Medical Center	Des Moines	Iowa	United States	50309
135	Medical Oncology and Hematology Associates at John Stoddard Cancer Center	Des Moines	Iowa	United States	50309
136	Medical Oncology and Hematology Associates at Mercy Cancer Center	Des Moines	Iowa	United States	50314
137	Mercy Cancer Center at Mercy Medical Center - Des Moines	Des Moines	Iowa	United States	50314
138	John Stoddard Cancer Center at Iowa Lutheran Hospital	Des Moines	Iowa	United States	50316
139	Mercy Cancer Center at Mercy Medical Center - North Iowa	Mason City	Iowa	United States	50401
140	McCreery Cancer Center at Ottumwa Regional	Ottumwa	Iowa	United States	52501
141	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa	United States	51101
142	Mercy Medical Center - Sioux City	Sioux City	Iowa	United States	51104
143	St. Luke's Regional Medical Center	Sioux City	Iowa	United States	51104
144	Cedar Valley Medical Specialists, PC - West Ridgeway Avenue	Waterloo	Iowa	United States	50702
145	Covenant Cancer Treatment Center	Waterloo	Iowa	United States	50702
146	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas	United States	66720
147	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas	United States	67801
148	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas	United States	67042
149	Cancer Center of Kansas-Independence	Independence	Kansas	United States	67301
150	Providence Medical Center	Kansas City	Kansas	United States	66112
151	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas	United States	67068
152	Lawrence Memorial Hospital	Lawrence	Kansas	United States	66044
153	Southwest Medical Center	Liberal	Kansas	United States	67901
154	Cancer Center of Kansas, PA - Newton	Newton	Kansas	United States	67114
155	Menorah Medical Center	Overland Park	Kansas	United States	66209
156	Johnson County Radiation Therapy	Overland Park	Kansas	United States	66210
157	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas	United States	67357
158	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas	United States	67124
159	Cancer Center of Kansas, PA - Salina	Salina	Kansas	United States	67042
160	Shawnee Mission Medical Center	Shawnee Mission	Kansas	United States	66204
161	Cotton-O'Neil Cancer Center	Topeka	Kansas	United States	66606
162	St. Francis Comprehensive Cancer Center	Topeka	Kansas	United States	66606
163	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas	United States	67152
164	Associates in Womens Health, PA - North Review	Wichita	Kansas	United States	67208
165	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas	United States	67208
166	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas	United States	67214
167	CCOP - Wichita	Wichita	Kansas	United States	67214
168	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
169	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas	United States	67156
170	Pennington Cancer Center at Baton Rouge General	Baton Rouge	Louisiana	United States	70806
171	Mary Bird Perkins Cancer Center - Baton Rouge	Baton Rouge	Louisiana	United States	70809
172	Ochsner Health Center - Bluebonnet	Baton Rouge	Louisiana	United States	70809
173	Terrebonne General Medical Center	Houma	Louisiana	United States	70360
174	MBCCOP - LSU Health Sciences Center	New Orleans	Louisiana	United States	70112
175	Medical Center of Louisiana - New Orleans	New Orleans	Louisiana	United States	70112
176	CCOP - Ochsner	New Orleans	Louisiana	United States	70121
177	Ochsner Cancer Institute at Ochsner Clinic Foundation	New Orleans	Louisiana	United States	70121
178	CancerCare of Maine at Eastern Maine Medical Center	Bangor	Maine	United States	04401
179	MaineGeneral Medical Center - Waterville	Waterville	Maine	United States	04901
180	St. Agnes Hospital Cancer Center	Baltimore	Maryland	United States	21229
181	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21231-2410
182	Upper Chesapeake Medical Center	Bel Air	Maryland	United States	21014
183	Union Hospital Cancer Program at Union Hospital	Elkton	Maryland	United States	21921
184	Frederick Memorial Hospital Regional Cancer Therapy Center	Frederick	Maryland	United States	21701
185	Kaiser Permanente Mid-Atlantic Medical Group-Largo Medical Facility	Largo	Maryland	United States	20774
186	Kaiser Permanente - Towson	Lutherville	Maryland	United States	21093
187	Kaiser Permanente Capital Area Medical Group - Shady Grove Facility	Rockville	Maryland	United States	20850
188	Tufts-NEMC Cancer Center	Boston	Massachusetts	United States	02111
189	Berkshire Hematology Oncology, PC	Pittsfield	Massachusetts	United States	01201
190	Morton Hospital & Medical Center	Taunton	Massachusetts	United States	02780
191	Hickman Cancer Center at Bixby Medical Center	Adrian	Michigan	United States	49221
192	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan	United States	48106-0995
193	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan	United States	48106
194	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan	United States	48123-2500
195	Green Bay Oncology, Limited - Escanaba	Escanaba	Michigan	United States	49431
196	Genesys Hurley Cancer Institute	Flint	Michigan	United States	48503
197	Hurley Medical Center	Flint	Michigan	United States	48503
198	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan	United States	48236
199	Dickinson County Healthcare System	Iron Mountain	Michigan	United States	49801
200	Foote Memorial Hospital	Jackson	Michigan	United States	49201
201	Borgess Medical Center	Kalamazoo	Michigan	United States	49001
202	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007-3731
203	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
204	Haematology-Oncology Associates of Ohio and Michigan, PC	Lambertville	Michigan	United States	48144
205	Sparrow Regional Cancer Center	Lansing	Michigan	United States	48912-1811
206	Community Cancer Center of Monroe	Monroe	Michigan	United States	48162
207	Mercy Memorial Hospital - Monroe	Monroe	Michigan	United States	48162
208	Northern Michigan Hospital	Petoskey	Michigan	United States	49770
209	William Beaumont Hospital - Royal Oak Campus	Royal Oak	Michigan	United States	48073
210	Seton Cancer Institute at Saint Mary's - Saginaw	Saginaw	Michigan	United States	48601
211	Lakeland Regional Cancer Care Center - St. Joseph	Saint Joseph	Michigan	United States	49085
212	Oncology Care Associates, PLLC	Saint Joseph	Michigan	United States	49085
213	St. John Macomb Hospital	Warren	Michigan	United States	48093
214		Alexandria	Minnesota	United States	56308
215	MeritCare Bemidji	Bemidji	Minnesota	United States	56601
216	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
217	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota	United States	55433
218	Duluth Clinic Cancer Center - Duluth	Duluth	Minnesota	United States	55805-1983
219	CCOP - Duluth	Duluth	Minnesota	United States	55805
220	Miller - Dwan Medical Center	Duluth	Minnesota	United States	55805
221	St. Luke's Hospital Cancer Care Center	Duluth	Minnesota	United States	55805
222	Fairview Southdale Hospital	Edina	Minnesota	United States	55435
223		Fergus Falls	Minnesota	United States	56537
224	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota	United States	55432
225	Hutchinson Area Health Care	Hutchinson	Minnesota	United States	55350
226	Meeker County Memorial Hospital	Litchfield	Minnesota	United States	55355
227	HealthEast Cancer Care at St. John's Hospital	Maplewood	Minnesota	United States	55109
228	Minnesota Oncology Hematology, PA - Maplewood	Maplewood	Minnesota	United States	55109
229	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota	United States	55407
230	Hennepin County Medical Center - Minneapolis	Minneapolis	Minnesota	United States	55415
231	Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota	United States	55422-2900
232	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
233	CentraCare Clinic - River Campus	Saint Cloud	Minnesota	United States	56303
234	Coborn Cancer Center	Saint Cloud	Minnesota	United States	56303
235	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota	United States	55416
236	Park Nicollet Cancer Center	Saint Louis Park	Minnesota	United States	55416
237	Regions Hospital Cancer Care Center	Saint Paul	Minnesota	United States	55101
238	HealthEast Cancer Care at St. Joseph's Hospital	Saint Paul	Minnesota	United States	55102
239	United Hospital	Saint Paul	Minnesota	United States	55102
240	St. Francis Cancer Center at St. Francis Medical Center	Shakopee	Minnesota	United States	55379
241	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
242	Willmar Cancer Center at Rice Memorial Hospital	Willmar	Minnesota	United States	56201
243	HealthEast Cancer Care at Woodwinds Health Campus	Woodbury	Minnesota	United States	55125
244	Minnesota Oncology Hematology, PA - Woodbury	Woodbury	Minnesota	United States	55125
245	Hattiesburg Clinic, PA at Forrest General	Hattiesburg	Mississippi	United States	39401
246	Hematology & Oncology Clinic	Hattiesburg	Mississippi	United States	39402
247	Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital	Cape Girardeau	Missouri	United States	63701
248	Saint Francis Medical Center	Cape Girardeau	Missouri	United States	63703
249	Independence Regional Health Center	Independence	Missouri	United States	64050
250	Truman Medical Center - Hospital Hill	Kansas City	Missouri	United States	64108
251	Saint Luke's Cancer Institute at Saint Luke's Hospital	Kansas City	Missouri	United States	64111
252	Kansas City Cancer Center at St. Joseph's Medical Mall	Kansas City	Missouri	United States	64114
253	St. Joseph Medical Center	Kansas City	Missouri	United States	64114
254	North Kansas City Hospital	Kansas City	Missouri	United States	64116
255	Parvin Radiation Oncology	Kansas City	Missouri	United States	64116
256	CCOP - Kansas City	Kansas City	Missouri	United States	64131
257	Radiation Oncology Associates of Kansas City at Northland Radiation Oncology Center	Kansas City	Missouri	United States	64154
258	Heartland Regional Medical Center	Saint Joseph	Missouri	United States	64506
259	Midwest Hematology Oncology Group, Incorporated	Saint Louis	Missouri	United States	63109
260	Missouri Baptist Cancer Center	Saint Louis	Missouri	United States	63131
261	Arch Medical Services, Incorporated at Center for Cancer Care and Research	Saint Louis	Missouri	United States	63141
262	CCOP - St. Louis-Cape Girardeau	Saint Louis	Missouri	United States	63141
263	David C. Pratt Cancer Center at St. John's Mercy	Saint Louis	Missouri	United States	63141
264	CCOP - Cancer Research for the Ozarks	Springfield	Missouri	United States	65802
265	St. John's Regional Health Center	Springfield	Missouri	United States	65804
266	Hulston Cancer Center at Cox Medical Center South	Springfield	Missouri	United States	65807
267	CCOP - Montana Cancer Consortium	Billings	Montana	United States	59101
268	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana	United States	59101
269	Northern Rockies Radiation Oncology Center	Billings	Montana	United States	59101
270	St. Vincent Healthcare Cancer Care Services	Billings	Montana	United States	59101
271	Billings Clinic - Downtown	Billings	Montana	United States	59107-7000
272	Bozeman Deaconess Cancer Center	Bozeman	Montana	United States	59715
273	St. James Healthcare Cancer Care	Butte	Montana	United States	59701
274	Big Sky Oncology	Great Falls	Montana	United States	59405-5309
275	Great Falls Clinic - Main Facility	Great Falls	Montana	United States	59405
276	Sletten Cancer Institute at Benefis Healthcare	Great Falls	Montana	United States	59405
277		Great Falls	Montana	United States	59405
278	St. Peter's Hospital	Helena	Montana	United States	59601
279	Glacier Oncology, PLLC	Kalispell	Montana	United States	59901
280	Kalispell Medical Oncology at KRMC	Kalispell	Montana	United States	59901
281	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
282	Community Medical Center	Missoula	Montana	United States	59801
283	Guardian Oncology and Center for Wellness	Missoula	Montana	United States	59804
284	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana	United States	59807-7877
285	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana	United States	59807
286	Good Samaritan Cancer Center at Good Samaritan Hospital	Kearney	Nebraska	United States	68848-1990
287	Cancer Resource Center - Lincoln	Lincoln	Nebraska	United States	68510
288	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska	United States	68106
289	Methodist Estabrook Cancer Center	Omaha	Nebraska	United States	68114
290	Immanuel Medical Center	Omaha	Nebraska	United States	68122
291	Alegant Health Cancer Center at Bergan Mercy Medical Center	Omaha	Nebraska	United States	68124
292	Creighton University Medical Center	Omaha	Nebraska	United States	68131-2197
293	Carson Tahoe Cancer Center at Carson Tahoe Regional Medical Center	Carson City	Nevada	United States	89703
294	University Medical Center of Southern Nevada	Las Vegas	Nevada	United States	89102
295	CCOP - Nevada Cancer Research Foundation	Las Vegas	Nevada	United States	89106
296	Veterans Affairs Medical Center - East Orange	East Orange	New Jersey	United States	07018-1095
297	Dizzy Gillespie Cancer Institute at Englewood Hospital and Medical Center	Englewood	New Jersey	United States	07631
298	St. Joseph's Hospital and Medical Center	Paterson	New Jersey	United States	07503
299	AtlantiCare Cancer Care Institute at AtlantiCare Regional Medical Center - Mainland Campus	Pomona	New Jersey	United States	08240
300	Valley Hospital - Ridgewood	Ridgewood	New Jersey	United States	07450
301	Somerset Medical Center	Somerville	New Jersey	United States	08876
302	Frederick R. and Betty M. Smith Cancer Treatment Center	Sparta	New Jersey	United States	07871
303	Franklin & Edith Scarpa Regional Cancer Center at South Jersey Healthcare	Vineland	New Jersey	United States	08360
304	Cancer Institute of New Jersey at Cooper - Voorhees	Voorhees	New Jersey	United States	08043
305	Underwood Memorial Hospital	Woodbury	New Jersey	United States	08096
306	Albert Einstein Cancer Center at Albert Einstein College of Medicine	Bronx	New York	United States	10461
307	Jacobi Medical Center	Bronx	New York	United States	10461
308	Our Lady of Mercy Medical Center Comprehensive Cancer Center	Bronx	New York	United States	10466
309	Finger Lakes Hematology and Oncology	Clifton Springs	New York	United States	14432
310	SUNY Upstate Medical University Hospital	Syracuse	New York	United States	13210
311	Mission Hospitals - Memorial Campus	Asheville	North Carolina	United States	28801
312	Blumenthal Cancer Center at Carolinas Medical Center	Charlotte	North Carolina	United States	28232-2861
313	Presbyterian Cancer Center at Presbyterian Hospital	Charlotte	North Carolina	United States	28233-3549
314	Batte Cancer Center at Northeast Medical Center	Concord	North Carolina	United States	28025
315	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina	United States	27534
316	Leo W. Jenkins Cancer Center at ECU Medical School	Greenville	North Carolina	United States	27835-6028
317	Pardee Memorial Hospital	Hendersonville	North Carolina	United States	28791
318	Kinston Medical Specialists	Kinston	North Carolina	United States	28501
319	Rutherford Hospital	Rutherfordton	North Carolina	United States	28139
320	Bismarck Cancer Center	Bismarck	North Dakota	United States	58501
321	Medcenter One Hospital Cancer Care Center	Bismarck	North Dakota	United States	58501
322	Mid Dakota Clinic, PC	Bismarck	North Dakota	United States	58501
323	St. Alexius Medical Center Cancer Center	Bismarck	North Dakota	United States	58502
324	CCOP - MeritCare Hospital	Fargo	North Dakota	United States	58122
325	MeritCare Broadway	Fargo	North Dakota	United States	58122
326	Altru Cancer Center at Altru Hospital	Grand Forks	North Dakota	United States	58201
327	Trinity CancerCare Center	Minot	North Dakota	United States	58701
328	McDowell Cancer Center at Akron General Medical Center	Akron	Ohio	United States	44307
329	Mary Rutan Hospital	Bellefontaine	Ohio	United States	43311
330	Wood County Oncology Center	Bowling Green	Ohio	United States	43402
331	Mercy Cancer Center at Mercy Medical Center	Canton	Ohio	United States	44708
332	Aultman Cancer Center at Aultman Hospital	Canton	Ohio	United States	44710-1799
333	Adena Regional Medical Center	Chillicothe	Ohio	United States	45601
334	Christ Hospital Cancer Center	Cincinnati	Ohio	United States	45219
335	Case Comprehensive Cancer Center	Cleveland	Ohio	United States	44106-5065
336	MetroHealth Cancer Care Center at MetroHealth Medical Center	Cleveland	Ohio	United States	44109
337	Cleveland Clinic Cancer Center at Fairview Hospital	Cleveland	Ohio	United States	44111
338	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio	United States	44195
339	Riverside Methodist Hospital Cancer Care	Columbus	Ohio	United States	43214-3998
340	CCOP - Columbus	Columbus	Ohio	United States	43215
341	Grant Medical Center Cancer Care	Columbus	Ohio	United States	43215
342	Mount Carmel Health - West Hospital	Columbus	Ohio	United States	43222
343	Doctors Hospital at Ohio Health	Columbus	Ohio	United States	43228
344	Grandview Hospital	Dayton	Ohio	United States	45405
345	Good Samaritan Hospital	Dayton	Ohio	United States	45406
346	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio	United States	45409
347	Samaritan North Cancer Care Center	Dayton	Ohio	United States	45415
348	Veterans Affairs Medical Center - Dayton	Dayton	Ohio	United States	45428
349	CCOP - Dayton	Dayton	Ohio	United States	45429
350	Grady Memorial Hospital	Delaware	Ohio	United States	43015
351	Blanchard Valley Medical Associates	Findlay	Ohio	United States	45840
352	Middletown Regional Hospital	Franklin	Ohio	United States	45005-1066
353	Community Oncology Group at Cleveland Clinic Cancer Center	Independence	Ohio	United States	44131
354	Charles F. Kettering Memorial Hospital	Kettering	Ohio	United States	45429
355	Fairfield Medical Center	Lancaster	Ohio	United States	43130
356	St. Rita's Medical Center	Lima	Ohio	United States	45801
357	Lima Memorial Hospital	Lima	Ohio	United States	45804
358	Strecker Cancer Center at Marietta Memorial Hospital	Marietta	Ohio	United States	45750
359	Northwest Ohio Oncology Center	Maumee	Ohio	United States	43537
360	St. Luke's Hospital	Maumee	Ohio	United States	43537
361	Licking Memorial Cancer Care Program at Licking Memorial Hospital	Newark	Ohio	United States	43055
362	St. Charles Mercy Hospital	Oregon	Ohio	United States	43616
363	Toledo Clinic - Oregon	Oregon	Ohio	United States	43616
364	Firelands Regional Medical Center	Sandusky	Ohio	United States	44870
365	North Coast Cancer Care, Incorporated	Sandusky	Ohio	United States	44870
366	Mercy Medical Center	Springfield	Ohio	United States	45504
367	Community Hospital of Springfield and Clark County	Springfield	Ohio	United States	45505
368	Flower Hospital Cancer Center	Sylvania	Ohio	United States	43560
369	Mercy Hospital of Tiffin	Tiffin	Ohio	United States	44883
370	Toledo Hospital	Toledo	Ohio	United States	43606
371	St. Vincent Mercy Medical Center	Toledo	Ohio	United States	43608
372	Medical University of Ohio Cancer Center	Toledo	Ohio	United States	43614
373	CCOP - Toledo Community Hospital	Toledo	Ohio	United States	43617
374	Toledo Clinic, Incorporated - Main Clinic	Toledo	Ohio	United States	43623
375	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio	United States	45373-1300
376	Fulton County Health Center	Wauseon	Ohio	United States	43567
377	Mount Carmel St. Ann's Cancer Center	Westerville	Ohio	United States	43081
378	Clinton Memorial Hospital	Wilmington	Ohio	United States	45177
379	Cleveland Clinic - Wooster	Wooster	Ohio	United States	44691
380	United States Air Force Medical Center - Wright-Patterson	Wright-Patterson Air Force Base	Ohio	United States	45433-5529
381	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio	United States	45385
382	Genesis - Good Samaritan Hospital	Zanesville	Ohio	United States	43701
383	Natalie Warren Bryant Cancer Center at St. Francis Hospital	Tulsa	Oklahoma	United States	74136
384	Rosenfeld Cancer Center at Abington Memorial Hospital	Abington	Pennsylvania	United States	19001
385	Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest	Allentown	Pennsylvania	United States	18105
386	St. Luke's Cancer Network at St. Luke's Hospital	Bethlehem	Pennsylvania	United States	18015
387	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania	United States	19010
388	Geisinger Cancer Institute at Geisinger Health	Danville	Pennsylvania	United States	17822-0001
389	Mercy Fitzgerald Hospital	Darby	Pennsylvania	United States	19023
390	Delaware County Regional Cancer Center at Delaware County Memorial Hospital	Drexel Hill	Pennsylvania	United States	19026
391	Oncology Hematology Associates of Northern Pennsylvania, PC at Hahne Regional Cancer Center	DuBois	Pennsylvania	United States	15801
392	Dale and Frances Hughes Cancer Center at Pocono Medical Center	East Stroudsburg	Pennsylvania	United States	18301
393	Easton Regional Cancer Center at Easton Hospital	Easton	Pennsylvania	United States	18042
394	Ephrata Cancer Center at Ephrata Community Hospital	Ephrata	Pennsylvania	United States	17522
395	Penn State Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania	United States	17033-0850
396	Richard G. Laube Cancer Center at ACMH	Kittanning	Pennsylvania	United States	16201
397	Lancaster General Hospital	Lancaster	Pennsylvania	United States	17604
398	Central Pennsylvania Hematology and Medical Oncology Associates, PC	Lemoyne	Pennsylvania	United States	17043
399	Lewistown Hospital	Lewistown	Pennsylvania	United States	17044
400	Riddle Memorial Hospital Cancer Center	Media	Pennsylvania	United States	19063
401	Cancer Center of Paoli Memorial Hospital	Paoli	Pennsylvania	United States	19301-1792
402	Abramson Cancer Center of the University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104-4283
403	Kimmel Cancer Center at Thomas Jefferson University - Philadelphia	Philadelphia	Pennsylvania	United States	19107-5541
404	Joan Karnell Cancer Center at Pennsylvania Hospital	Philadelphia	Pennsylvania	United States	19107
405	Fox Chase Cancer Center - Philadelphia	Philadelphia	Pennsylvania	United States	19111-2497
406	Frankford Hospital Cancer Center - Torresdale Campus	Philadelphia	Pennsylvania	United States	19114
407	Albert Einstein Cancer Center	Philadelphia	Pennsylvania	United States	19141
408	UPMC Cancer Centers	Pittsburgh	Pennsylvania	United States	15232
409	Pottstown Memorial Regional Cancer Center	Pottstown	Pennsylvania	United States	19464
410	McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center	Reading	Pennsylvania	United States	19612-6052
411	Guthrie Cancer Center at Guthrie Clinic Sayre	Sayre	Pennsylvania	United States	18840
412	Mercy Hospital Cancer Center - Scranton	Scranton	Pennsylvania	United States	18501
413	Hematology and Oncology Associates of Northeastern Pennsylvania	Scranton	Pennsylvania	United States	18510
414	Grand View Hospital	Sellersville	Pennsylvania	United States	18960
415	Geisinger Medical Group - Scenery Park	State College	Pennsylvania	United States	16801
416	Mount Nittany Medical Center	State College	Pennsylvania	United States	16803
417	Associates in Hematology-Oncology, PC at Crozer Regional Cancer Center	Upland	Pennsylvania	United States	19013
418	Chester County Hospital	West Chester	Pennsylvania	United States	19380
419	Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center	Wilkes-Barre	Pennsylvania	United States	18711
420	Susquehanna Cancer Center at Divine Providence Hospital	Williamsport	Pennsylvania	United States	17701
421	CCOP - Main Line Health	Wynnewood	Pennsylvania	United States	19096
422	Lankenau Cancer Center at Lankenau Hospital	Wynnewood	Pennsylvania	United States	19096
423	York Cancer Center at Apple Hill Medical Center	York	Pennsylvania	United States	17405
424	AnMed Cancer Center	Anderson	South Carolina	United States	29621
425	McLeod Regional Medical Center	Florence	South Carolina	United States	29501
426	CCOP - Greenville	Greenville	South Carolina	United States	29615
427	CCOP - Upstate Carolina	Spartanburg	South Carolina	United States	29303
428	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina	United States	29303
429	Oncology Services of Aberdeen	Aberdeen	South Dakota	United States	57401
430	Rapid City Regional Hospital	Rapid City	South Dakota	United States	57701
431	Avera Cancer Institute	Sioux Falls	South Dakota	United States	57105
432	Medical X-Ray Center, PC	Sioux Falls	South Dakota	United States	57105
433	Sanford Cancer Center at Sanford USD Medical Center	Sioux Falls	South Dakota	United States	57117-5039
434	Green Mountain Oncology Group	Bennington	Vermont	United States	05201
435	Martha Jefferson Hospital Cancer Care Center	Charlottesville	Virginia	United States	22901
436	University of Virginia Cancer Center	Charlottesville	Virginia	United States	22908
437	Danville Regional Medical Center	Danville	Virginia	United States	24541
438	Kaiser Permanente Medical Center - Fair Oaks	Fairfax	Virginia	United States	22033
439	Fredericksburg Oncology, Incorporated	Fredericksburg	Virginia	United States	22401
440	Veterans Affairs Medical Center - Richmond	Richmond	Virginia	United States	23249
441	Virginia Commonwealth University Massey Cancer Center	Richmond	Virginia	United States	23298-0037
442	St. Francis Hospital	Federal Way	Washington	United States	98003
443	Good Samaritan Cancer Center	Puyallup	Washington	United States	98372
444	Rockwood Clinic Cancer Treatment Center	Spokane	Washington	United States	99204-2967
445	Franciscan Cancer Center at St. Joseph Medical Center	Tacoma	Washington	United States	98405-3004
446	Allenmore Hospital	Tacoma	Washington	United States	98405
447	CCOP - Northwest	Tacoma	Washington	United States	98405
448	MultiCare Regional Cancer Center at Tacoma General Hospital	Tacoma	Washington	United States	98405
449	St. Clare Hospital	Tacoma	Washington	United States	98499
450	Edwards Comprehensive Cancer Center at Cabell Huntington Hospital	Huntington	West Virginia	United States	25701
451	Langlade Memorial Hospital	Antigo	Wisconsin	United States	54409
452	Fox Valley Hematology and Oncology - East Grant Street	Appleton	Wisconsin	United States	54911-3496
453	Center for Cancer Treatment & Prevention at Sacred Heart Hospital	Eau Claire	Wisconsin	United States	54701
454	Marshfield Clinic Cancer Care at Regional Cancer Center	Eau Claire	Wisconsin	United States	54701
455	Vince Lombardi Cancer Center at Aurora Lakeland Medical Center - Elkhorn	Elkhorn	Wisconsin	United States	53121
456	Central Wisconsin Cancer Program at Agnesian HealthCare	Fond Du Lac	Wisconsin	United States	54935
457	Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin	United States	54301-3526
458	Green Bay Oncology, Limited at St. Mary's Hospital	Green Bay	Wisconsin	United States	54303
459	St. Mary's Hospital Medical Center - Green Bay	Green Bay	Wisconsin	United States	54303
460	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin	United States	54307-3508
461	Vince Lombardi Cancer Clinic - Green Bay at Aurora BayCare Medical Center	Green Bay	Wisconsin	United States	54311
462	Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center	La Crosse	Wisconsin	United States	54601
463	Dean Medical Center - Madison	Madison	Wisconsin	United States	53717
464	University of Wisconsin Paul P. Carbone Comprehensive Cancer Center	Madison	Wisconsin	United States	53792-6164
465	Holy Family Memorial Medical Center Cancer Care Center	Manitowoc	Wisconsin	United States	54221-1450
466	Bay Area Cancer Care Center at Bay Area Medical Center	Marinette	Wisconsin	United States	54143
467	Marshfield Clinic - Marshfield Center	Marshfield	Wisconsin	United States	54449
468	Saint Joseph's Hospital	Marshfield	Wisconsin	United States	54449
469	Aurora Sinai Medical Center	Milwaukee	Wisconsin	United States	53201-0342
470	Medical Consultants, Limited	Milwaukee	Wisconsin	United States	53215
471	Froedtert Hospital and Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
472	Medical College of Wisconsin Cancer Center	Milwaukee	Wisconsin	United States	53226
473	Marshfield Clinic - Lakeland Center	Minocqua	Wisconsin	United States	54548
474	Green Bay Oncology, Limited - Oconto Falls	Oconto Falls	Wisconsin	United States	54154
475	Ministry Medical Group at Saint Mary's Hospital	Rhinelander	Wisconsin	United States	54501
476	Marshfield Clinic - Indianhead Center	Rice Lake	Wisconsin	United States	54868
477	Saint Michael's Hospital Cancer Center	Stevens Point	Wisconsin	United States	54481
478	Green Bay Oncology, Limited - Sturgeon Bay	Sturgeon Bay	Wisconsin	United States	54235
479	Marshfield Clinic - Wausau Center	Wausau	Wisconsin	United States	54401
480	University of Wisconcin Cancer Center at Aspirus Wausau Hospital	Wausau	Wisconsin	United States	54401
481	Marshfield Clinic - Weston Center	Weston	Wisconsin	United States	54476
482	Marshfield Clinic - Wisconsin Rapids Center	Wisconsin Rapids	Wisconsin	United States	54494
483	Welch Cancer Center at Sheridan Memorial Hospital	Sheridan	Wyoming	United States	82801

Sponsors and Collaborators

• Eastern Cooperative Oncology Group
• National Cancer Institute (NCI)

Investigators

• Study Chair: Brad S. Kahl, MD, University of Wisconsin, Madison

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eastern Cooperative Oncology Group
• ClinicalTrials.gov Identifier: NCT00075946
• Other Study ID Numbers: CDR0000346359; U10CA021115; ECOG-E4402
• First Posted: Jan 14, 2004
• Last Update Posted: Jun 10, 2022
• Last Verified: Jun 1, 2022

• Keywords provided by Eastern Cooperative Oncology Group: stage III grade 1 follicular lymphoma; stage III grade 2 follicular lymphoma; stage IV grade 1 follicular lymphoma; stage IV grade 2 follicular lymphoma; stage III small lymphocytic lymphoma; stage III marginal zone lymphoma; stage IV small lymphocytic lymphoma; stage IV marginal zone lymphoma; extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue; nodal marginal zone B-cell lymphoma; splenic marginal zone lymphoma
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Rituximab

Study Results

Participant Flow

Recruitment Details	The study was opened on Nov 21, 2003, and closed on Sept 12, 2008, with final accrual of 545 patients.
Pre-assignment Detail	Patients received induction rituximab IV once a week for 4 weeks. Patients were re-evaluated 9 weeks after the completion of induction rituximab. Patients with a partial or complete response to induction rituximab were randomized to one of the two treatment arms, stratified on histology (follicular vs other), age, and time from diagnosis.

Arm/Group Title	Rituximab Retreatment: Follicular Patients	Rituximab Scheduled: Follicular Patients	Rituximab Retreatment: Non-Follicular Patients	Rituximab Scheduled: Non-Follicular Patients	Enrolled But Not Randomized
Arm/Group Description	Following induction rituximab, patients who were randomized to this arm received rituximab IV once a week for 4 weeks upon disease progression provided time to progression is more than 6 months. Follicular and non-follicular patients were analyzed separately per protocol.	Following induction rituximab, patients who were randomized to this arm received a single dose of rituximab IV once every 13 weeks until disease progression and in the absence of unacceptable toxicity. Follicular and non-follicular patients were analyzed separately per protocol.	Following induction rituximab, patients who were randomized to this arm received rituximab IV once a week for 4 weeks upon disease progression provided time to progression is more than 6 months. Follicular and non-follicular patients were analyzed separately per protocol.	Following induction rituximab, patients who were randomized to this arm received a single dose of rituximab IV once every 13 weeks until disease progression and in the absence of unacceptable toxicity. Follicular and non-follicular patients were analyzed separately per protocol.	Patients who were enrolled in the study but not proceed to randomization. These could include patients with undetermined histology as well as those who did not achieve response (PR or CR) after induction rituximab.
Period Title: Overall Study
STARTED	148	151	28	30	188
Treated and With Toxicity Data Available	142	148	27	29	154
Included in Primary Analysis	143	146	23	29	0
COMPLETED	0	0	0	0	0
NOT COMPLETED	148	151	28	30	188

Baseline Characteristics

Arm/Group Title	Rituximab Retreatment: Follicular Patients	Rituximab Scheduled: Follicular Patients	Rituximab Retreatment: Non-Follicular Patients	Rituximab Scheduled: Non-Follicular Patients	Total
Arm/Group Description	Following induction rituximab, patients who were randomized to this arm received rituximab IV once a week for 4 weeks upon disease progression provided time to progression is more than 6 months. Follicular and non-follicular patients were analyzed separately per protocol.	Following induction rituximab, patients who were randomized to this arm received a single dose of rituximab IV once every 13 weeks until disease progression and in the absence of unacceptable toxicity. Follicular and non-follicular patients were analyzed separately per protocol.	Following induction rituximab, patients who were randomized to this arm received rituximab IV once a week for 4 weeks upon disease progression provided time to progression is more than 6 months. Follicular and non-follicular patients were analyzed separately per protocol.	Following induction rituximab, patients who were randomized to this arm received a single dose of rituximab IV once every 13 weeks until disease progression and in the absence of unacceptable toxicity. Follicular and non-follicular patients were analyzed separately per protocol.	Total of all reporting groups
Overall Participants	143	146	23	29	341
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	59	58	61	65	60
Sex: Female, Male (Count of Participants)
Female	76 53.1%	80 54.8%	16 69.6%	14 48.3%	186 54.5%
Male	67 46.9%	66 45.2%	7 30.4%	15 51.7%	155 45.5%

Outcome Measures

1. Primary Outcome

Title	Time to Rituximab Failure (TTRF)
Description	TTRF is defined as the time from randomization until any one of the following criteria are met, and censored at last disease assessment for cases who have not experienced failure (with the cut-off date for final analysis of 11/1/2011): 1. No response (partial response (PR) or complete response (CR)) to rituximab retreatment (Arm A treatment). 2. Time to progression < 26 weeks from day 1 of most recent rituximab treatment. 3. Initiation of alternative therapy. 4. Inability to complete protocol therapy (due to adverse events, patient preference, or any other reason, including death).
Time Frame	Assessed (by restaging CT scans) 26 weeks ± 2 weeks from each rituximab treatment (including induction), counting the first rituximab dose as Day 1, until rituximab failure observed or July 17, 2013, whichever occurred first.

Outcome Measure Data

Analysis Population Description

Eligible patients who were randomized to one of the two arms for maintenance therapy.

Arm/Group Title	Rituximab Retreatment: Follicular Patients	Rituximab Scheduled: Follicular Patients	Rituximab Retreatment: Non-Follicular Patients	Rituximab Scheduled: Non-Follicular Patients
Arm/Group Description	Following induction rituximab, patients who were randomized to this arm received rituximab IV once a week for 4 weeks upon disease progression provided time to progression is more than 6 months. Follicular and non-follicular patients were analyzed separately per protocol.	Following induction rituximab, patients who were randomized to this arm received a single dose of rituximab IV once every 13 weeks until disease progression and in the absence of unacceptable toxicity. Follicular and non-follicular patients were analyzed separately per protocol.	Following induction rituximab, patients who were randomized to this arm received rituximab IV once a week for 4 weeks upon disease progression provided time to progression is more than 6 months. Follicular and non-follicular patients were analyzed separately per protocol.	Following induction rituximab, patients who were randomized to this arm received a single dose of rituximab IV once every 13 weeks until disease progression and in the absence of unacceptable toxicity. Follicular and non-follicular patients were analyzed separately per protocol.
Measure Participants	143	146	23	29
Median (95% Confidence Interval) [years]	3.92	4.32	1.39	4.83

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rituximab Retreatment: Follicular Patients, Rituximab Scheduled: Follicular Patients
	Comments	The primary analysis is to compare the time to rituximab failure (TTRF) between the retreatment arm and the scheduled arm in follicular patients.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.33
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.3
	Confidence Interval	(2-Sided) 95%; 0.90 to 1.88
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio is for Rituximab Retreatment Arm/Rituximab Scheduled Arm in follicular patients.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Rituximab Retreatment: Non-Follicular Patients, Rituximab Scheduled: Non-Follicular Patients
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.012
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	2.75
	Confidence Interval	(2-Sided) 95%; 1.22 to 6.19
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio is for Rituximab Retreatment Arm/Rituximab Scheduled Arm in non-follicular patients.

2. Secondary Outcome

Title	Time to First Cytotoxic Therapy (TTFC)
Description	TTFC is defined as the time from randomization to the time of first cytotoxic therapy (chemo and radio therapy), and censored as last follow-up time if no cytotoxic therapy has been used. Since median TTFC was not reached in 3 out of the 4 groups, 3-year TTFC was reported which was defined as the probability of not starting first cytotoxic therapy at 3 years.
Time Frame	Assessed every 13 weeks until rituximab failure observed or August 2013, whichever occurred first.

Outcome Measure Data

Analysis Population Description

Patients who were correctly randomized to one of the two maintenance arms.

Arm/Group Title	Rituximab Retreatment: Follicular Patients	Rituximab Scheduled: Follicular Patients	Rituximab Retreatment: Non-Follicular Patients	Rituximab Scheduled: Non-Follicular Patients
Arm/Group Description	Following induction rituximab, patients who were randomized to this arm received rituximab IV once a week for 4 weeks upon disease progression provided time to progression is more than 6 months. Follicular and non-follicular patients were analyzed separately per protocol.	Following induction rituximab, patients who were randomized to this arm received a single dose of rituximab IV once every 13 weeks until disease progression and in the absence of unacceptable toxicity. Follicular and non-follicular patients were analyzed separately per protocol.	Following induction rituximab, patients who were randomized to this arm received rituximab IV once a week for 4 weeks upon disease progression provided time to progression is more than 6 months. Follicular and non-follicular patients were analyzed separately per protocol.	Following induction rituximab, patients who were randomized to this arm received a single dose of rituximab IV once every 13 weeks until disease progression and in the absence of unacceptable toxicity. Follicular and non-follicular patients were analyzed separately per protocol.
Measure Participants	143	146	23	29
Number (95% Confidence Interval) [probability]	0.84	0.95	0.72	1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rituximab Retreatment: Follicular Patients, Rituximab Scheduled: Follicular Patients
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	3.21
	Confidence Interval	(2-Sided) 95%; 1.45 to 7.13
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio is for Rituximab Retreatment Arm/Rituximab Scheduled Arm in follicular patients.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Rituximab Retreatment: Non-Follicular Patients, Rituximab Scheduled: Non-Follicular Patients
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments
	Method	Log Rank
	Comments

3. Secondary Outcome

Title	Overall Health-related Quality of Life (HRQL) at 6 Month After Randomization
Description	The overall HRQL was measured by the change in Functional Assessment of Cancer Therapy - General (FACT-G) from baseline to 6 months after randomization. The FACT-G is a 27-item assessment used to measure HRQL, specifically, physical, functional, social and emotional well-being. The total score ranges from 0 to 108, with higher scores indicating better HRQL.
Time Frame	Assessed at baseline and 6 months after randomization.

Outcome Measure Data

Analysis Population Description

Patients with patient-reported outcomes (PRO) data available.

Arm/Group Title	Arm A: Rituximab Retreatment	Arm B: Rituximab Scheduled
Arm/Group Description	Following induction rituximab, patients who were randomized to this arm received rituximab IV once a week for 4 weeks upon disease progression provided time to progression is more than 6 months.	Following induction rituximab, patients who were randomized to this arm received a single dose of rituximab IV once every 13 weeks until disease progression and in the absence of unacceptable toxicity.
Measure Participants	128	125
Mean (Standard Deviation) [units on a scale]	1.04 (12.82)	-0.71 (9.38)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rituximab Retreatment: Follicular Patients, Rituximab Scheduled: Follicular Patients
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.270
	Comments
	Method	t-test, 2 sided
	Comments

Adverse Events

Time Frame	Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
Arm/Group Title	Arm I: Induction Rituximab		Arm A: Rituximab Retreatment		Arm B: Rituximab Scheduled
Arm/Group Description	Patients received rituximab IV once a week for 4 weeks. Patients were re-evaluated 9 weeks after the completion of induction rituximab. Patients with a partial or complete response to induction rituximab were randomized to one of the two treatment arms.		Following induction rituximab, patients who were randomized to this arm received rituximab IV once a week for 4 weeks upon disease progression provided time to progression is more than 6 months.		Following induction rituximab, patients who were randomized to this arm received a single dose of rituximab IV once every 13 weeks until disease progression and in the absence of unacceptable toxicity.
All Cause Mortality
	Arm I: Induction Rituximab		Arm A: Rituximab Retreatment		Arm B: Rituximab Scheduled
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm I: Induction Rituximab		Arm A: Rituximab Retreatment		Arm B: Rituximab Scheduled
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/500 (4.6%)		5/169 (3%)		10/177 (5.6%)
Blood and lymphatic system disorders
Febrile neutropenia	1/500 (0.2%)		0/169 (0%)		0/177 (0%)
Cardiac disorders
Ventricular arrhythmia	1/500 (0.2%)		0/169 (0%)		0/177 (0%)
Heart failure	0/500 (0%)		0/169 (0%)		0/177 (0%)
Ear and labyrinth disorders
Hearing impaired	0/500 (0%)		0/169 (0%)		1/177 (0.6%)
General disorders
Fatigue	2/500 (0.4%)		1/169 (0.6%)		3/177 (1.7%)
Fever	0/500 (0%)		0/169 (0%)		1/177 (0.6%)
Non-cardiac chest pain	1/500 (0.2%)		0/169 (0%)		0/177 (0%)
Immune system disorders
Anaphylaxis	2/500 (0.4%)		0/169 (0%)		0/177 (0%)
Cytokine release syndrome	8/500 (1.6%)		0/169 (0%)		0/177 (0%)
Infections and infestations
Peripheral nerve infection	1/500 (0.2%)		0/169 (0%)		0/177 (0%)
Infections and infestations - Other, spe	0/500 (0%)		0/169 (0%)		1/177 (0.6%)
Investigations
Lymphocyte count decreased	0/500 (0%)		0/169 (0%)		1/177 (0.6%)
Neutrophil count decreased	2/500 (0.4%)		2/169 (1.2%)		0/177 (0%)
Platelet count decreased	0/500 (0%)		1/169 (0.6%)		0/177 (0%)
Metabolism and nutrition disorders
Hyperglycemia	1/500 (0.2%)		0/169 (0%)		0/177 (0%)
Musculoskeletal and connective tissue disorders
Generalized muscle weakness	0/500 (0%)		0/169 (0%)		1/177 (0.6%)
Back pain	1/500 (0.2%)		0/169 (0%)		0/177 (0%)
Nervous system disorders
Encephalopathy	0/500 (0%)		0/169 (0%)		1/177 (0.6%)
Syncope	1/500 (0.2%)		1/169 (0.6%)		0/177 (0%)
Neuralgia	1/500 (0.2%)		0/169 (0%)		0/177 (0%)
Psychiatric disorders
Insomnia	0/500 (0%)		0/169 (0%)		1/177 (0.6%)
Anxiety	1/500 (0.2%)		0/169 (0%)		0/177 (0%)
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain	0/500 (0%)		0/169 (0%)		1/177 (0.6%)
Dyspnea	1/500 (0.2%)		0/169 (0%)		0/177 (0%)
Respiratory, thoracic and mediastinal di	1/500 (0.2%)		0/169 (0%)		0/177 (0%)
Skin and subcutaneous tissue disorders
Rash maculo-papular	1/500 (0.2%)		0/169 (0%)		0/177 (0%)
Urticaria	2/500 (0.4%)		0/169 (0%)		0/177 (0%)
Vascular disorders
Hypertension	0/500 (0%)		1/169 (0.6%)		1/177 (0.6%)
Other (Not Including Serious) Adverse Events
	Arm I: Induction Rituximab		Arm A: Rituximab Retreatment		Arm B: Rituximab Scheduled
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	36/500 (7.2%)		5/169 (3%)		14/177 (7.9%)
General disorders
Fatigue	36/500 (7.2%)		5/169 (3%)		14/177 (7.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.