S0016 Combination Chemotherapy With Monoclonal Antibody Therapy in Newly Diagnosed Non-Hodgkin's Lymphoma

• Sponsor: Southwest Oncology Group (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT00006721
• Collaborator: National Cancer Institute (NCI) (NIH), Cancer and Leukemia Group B (Other), Eastern Cooperative Oncology Group (Other)
• Enrollment: 571
• Locations: 259
• Arms: 3
• Duration (Months): 267
• Patients Per Site: 2.2
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies can locate tumor cells and either kill them or deliver radioactive tumor-killing substances to them without harming normal cells. It is not yet known which monoclonal antibody plus combination chemotherapy regimen is more effective in treating non-Hodgkin's lymphoma.

PURPOSE: This randomized phase III trial is comparing 2 different monoclonal antibodies given together with combination chemotherapy to see how well they work in treating patients with newly-diagnosed non-Hodgkin's lymphoma.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Biological: rituximab; Drug: cyclophosphamide; Drug: doxorubicin; Drug: prednisone; Drug: vincristine; Radiation: tositumomab	Phase 3

Detailed Description

OBJECTIVES:

• Compare the progression-free survival and overall survival of patients with newly diagnosed follicular non-Hodgkin's lymphoma treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with or without either rituximab or iodine I 131 tositumomab (monoclonal antibody anti-B1). (CHOP chemotherapy alone arm closed to accrual as of 12/15/02)

• Compare the response rate of these patients treated with these regimens.

• Compare the toxic effects of these regimens in these patients.

• Compare the molecular remission rates of this patient population treated with these regimens.

• Determine the incidence and time to development of human anti-mouse antibody positivity.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to whether microglobulin is greater than upper limit of normal (yes vs no). Patients are randomized to 1 of 3 treatment arms. (Arm I closed to accrual as of 12/15/02)

• Arm I (CHOP only): Patients receive cyclophosphamide IV over 15 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on day 1. Patients also receive oral prednisone daily on days 1-5. Treatment continues every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. (Arm I closed to accrual as of 12/15/02)

• Arm II (CHOP + rituximab): Patients receive cyclophosphamide IV over 15 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on days 8, 29, 50, 71, 92, and 113. Patients also receive oral prednisone daily on days 8-12, 29-33, 50-54, 71-75, and 113-117 and rituximab IV over 4-6 hours on days 1, 6, 48, 90, 134, and

• Arm III (CHOP + tositumomab): Patients receive chemotherapy as in arm I and tositumomab (monoclonal antibody anti-B1) IV over 1 hour followed by iodine I 131 tositumomab IV over 20 minutes on days 134 and 141.

Patients are followed on day 200, at 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: Approximately 500 patients (250 per treatment arm) will be accrued for this study within 5.5 years. (Arm I closed to accrual as of 12/15/02)

Study Design

• Study Type: Interventional
• Actual Enrollment: 571 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase III Trial of CHOP Plus Rituximab vs CHOP Plus Iodine-131-Labeled Monoclonal Anti-B1 Antibody (Tositumomab) for Treatment of Newly Diagnosed Follicular Non-Hodgkin's Lymphomas
• Study Start Date: Mar 1, 2001
• Actual Primary Completion Date: Sep 1, 2011
• Anticipated Study Completion Date: Jun 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm I (CHOP only) Patients receive cyclophosphamide IV over 15 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on day 1. Patients also receive oral prednisone daily on days 1-5. Treatment continues every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. (Arm I closed to accrual as of 12/15/02)	Drug: cyclophosphamide; Given IV; Other Names: cytoxan ; Drug: doxorubicin; Given IV; Other Names: adriamycin ; Drug: prednisone; Given orally; Other Names: steroid ; Drug: vincristine; Given IV; Other Names: oncovin
Experimental: Arm II (CHOP + rituximab) Patients receive cyclophosphamide IV over 15 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on days 8, 29, 50, 71, 92, and 113. Patients also receive oral prednisone daily on days 8-12, 29-33, 50-54, 71-75, and 113-117 and rituximab IV over 4-6 hours on days 1, 6, 48, 90, 134, and 141.	Biological: rituximab; Given IV; Other Names: rituxan ; Drug: cyclophosphamide; Given IV; Other Names: cytoxan ; Drug: doxorubicin; Given IV; Other Names: adriamycin ; Drug: prednisone; Given orally; Other Names: steroid ; Drug: vincristine; Given IV; Other Names: oncovin
Experimental: Arm III (CHOP + tositumomab) Patients receive chemotherapy as in arm I and tositumomab (monoclonal antibody anti-B1) IV over 1 hour followed by iodine I 131 tositumomab IV over 20 minutes on days 134 and 141.	Drug: cyclophosphamide; Given IV; Other Names: cytoxan ; Drug: doxorubicin; Given IV; Other Names: adriamycin ; Drug: prednisone; Given orally; Other Names: steroid ; Drug: vincristine; Given IV; Other Names: oncovin ; Radiation: tositumomab; Given IV

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival at 2 Years [0-2 years]

   Measured from time of registration to date of of first observation of progression/relapse, or death due to any cause, or last contact date

2. Progression-free Survival at 5 Years [0-5 years]

   Measured from time of registration to date of of first observation of progression/relapse, or death due to any cause, or last contact date

3. Overall Survival at 2 Years [0-2 years]

   Measured from date of registration to date of death due to any cause

4. Overall Survival at 5 Years [0-5 years]

   Measured from date of registration to date of death due to any cause

Secondary Outcome Measures

1. Objective Response (Confirmed and Unconfirmed Complete and Partial Responses) [Assessed 200 days and 365 days after initiation of therapy and then every 6 months until death]

   Complete Response(CR) is a complete disappearance of all disease with the exception of nodes. No new lesions. previously enlarged organs must have regressed and not be palpable. Bone marrow(BM) must be negative if positive at baseline. Normalization of markers. CR Unconfirmed (CRU) does not qualify for CR above, due to a residual nodal mass or an indeterminate BM. Partial Response(PR) is a 50% decrease in the sum of products of greatest diameters (SPD) for up to 6 identified dominant lesions, including spleenic and hepatic nodules from baseline. No new lesions and no increase in the size of liver, spleen or other nodes.

2. Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug [Patients were assessed for adverse events at end of cycle 1-6 of CHOP or R-CHOP, the end of cycle 1-6 of CHOP and once 2 weeks after the completion of I-131 treatment. For either arm, once 3 months after removal from protocol treatment]

   Adverse Events (AEs) are reported by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 2.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal

Eligibility Criteria

Criteria

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

DISEASE CHARACTERISTICS:

• Histologically confirmed previously untreated bulky stage II or stage III or IV follicular non-Hodgkin's lymphoma

• Grade I-III disease

• Cluster of differentiation antigen 20 (CD20) antigen positive

• Fewer than 5,000/mm^3 circulating lymphoid cells on a white blood cell (WBC) differential count

• Bidimensionally measurable disease

• Bone marrow aspiration and biopsy within the past 42 days

• No clinical evidence of central nervous system (CNS) involvement by lymphoma

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Zubrod 0-2

Life expectancy:

• Not specified

Hematopoietic:

• See Disease Characteristics

• Granulocyte count greater than 1,500/mm^3

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

Hepatic:

• Not specified

Renal:

• Not specified

Cardiovascular:

• No impaired cardiac status, including:

• Severe coronary artery disease

• Cardiomyopathy

• Congestive heart failure

• Serious arrhythmia

• Ejection fraction at least lower limit of normal by Multi Gated Acquisition Scan (MUGA) or 2-D echocardiogram for questionable cardiac history

Other:

• No hypersensitivity to iodine

• Not pregnant or nursing

• Fertile patients must use effective contraception during and for 6 months after study participation

• HIV negative

• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior monoclonal antibodies for cancer

Chemotherapy:

• No prior chemotherapy for lymphoma

• Prior prednisone for non-lymphoma related illnesses allowed

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy for lymphoma

Surgery:

• See Disease Characteristics

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alaska Regional Hospital Cancer Center	Anchorage	Alaska	United States	99508
2	Fairbanks Cancer Treatment Center at Fairbanks Memorial Hospital	Fairbanks	Alaska	United States	99701
3	Hembree Mercy Cancer Center at St. Edward Mercy Medical Center	Fort Smith	Arkansas	United States	72903
4	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
5	Alta Bates Summit Comprehensive Cancer Center	Berkeley	California	United States	94704
6	Peninsula Medical Center	Burlingame	California	United States	94010
7	Marin Cancer Institute at Marin General Hospital	Greenbrae	California	United States	94904
8	Sutter Health - Western Division Cancer Research Group	Greenbrae	California	United States	94904
9	Desert Regional Medical Center Comprehensive Cancer Center	Palm Springs	California	United States	92262
10	University of California Davis Cancer Center	Sacramento	California	United States	95817
11	California Pacific Medical Center - California Campus	San Francisco	California	United States	94118
12	Stanford Cancer Center	Stanford	California	United States	94305-5824
13	Sutter Solano Medical Center	Vallejo	California	United States	94589
14	Helen and Harry Gray Cancer Center at Hartford Hospital	Hartford	Connecticut	United States	06102-5037
15	Lombardi Comprehensive Cancer Center at Georgetown University Medical Center	Washington	District of Columbia	United States	20007
16	Center for Cancer Care and Research at Watson Clinic, LLP	Lakeland	Florida	United States	33805
17	Sacred Heart Cancer Center at Sacred Heart Hospital	Pensacola	Florida	United States	32504
18	West Florida Cancer Institute at West Florida Hospital - Pensacola	Pensacola	Florida	United States	32514
19	Piedmont Hospital	Atlanta	Georgia	United States	30309
20	Northside Hospital Cancer Center	Atlanta	Georgia	United States	30342-1611
21	Saint Joseph's Hospital of Atlanta	Atlanta	Georgia	United States	30342-1701
22	CCOP - Atlanta Regional	Atlanta	Georgia	United States	30342
23	WellStar Cobb Hospital	Austell	Georgia	United States	30106
24	Charles B. Eberhart Cancer Center at DeKalb Medical Center	Decatur	Georgia	United States	30033
25	Dwight David Eisenhower Army Medical Center	Fort Gordon	Georgia	United States	30905-5650
26	Northeast Georgia Medical Center	Gainesville	Georgia	United States	30501
27	Gwinnett Medical Center	Lawrenceville	Georgia	United States	30045
28	Kennestone Cancer Center at Wellstar Kennestone Hospital	Marietta	Georgia	United States	30060
29	Southern Regional Medical Center	Riverdale	Georgia	United States	30274-2600
30	Pearlman Comprehensive Cancer Center at South Georgia Medical Center	Valdosta	Georgia	United States	31603
31	Tripler Army Medical Center	Honolulu	Hawaii	United States	96859
32	Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center	Boise	Idaho	United States	83706
33	Mountain States Tumor Institute at St. Luke's Regional Medical Center	Boise	Idaho	United States	83712
34	Saint Anthony's Hospital at Saint Anthony's Health Center	Alton	Illinois	United States	62002
35	Rush-Copley Cancer Care Center	Aurora	Illinois	United States	60504
36	St. Joseph Medical Center	Bloomington	Illinois	United States	61701
37	Graham Hospital	Canton	Illinois	United States	61520
38	Memorial Hospital	Carthage	Illinois	United States	62321
39	University of Illinois Cancer Center	Chicago	Illinois	United States	60612-7243
40	University of Chicago Cancer Research Center	Chicago	Illinois	United States	60637-1470
41	Decatur Memorial Hospital Cancer Care Institute	Decatur	Illinois	United States	62526
42	Eureka Community Hospital	Eureka	Illinois	United States	61530
43	Galesburg Clinic, PC	Galesburg	Illinois	United States	61401
44	Galesburg Cottage Hospital	Galesburg	Illinois	United States	61401
45	Mason District Hospital	Havana	Illinois	United States	62644
46	Veterans Affairs Medical Center - Hines	Hines	Illinois	United States	60141
47	Hopedale Medical Complex	Hopedale	Illinois	United States	61747
48	Joliet Oncology-Hematology Associates, Limited - West	Joliet	Illinois	United States	60435
49	McDonough District Hospital	Macomb	Illinois	United States	61455
50	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois	United States	60153
51	Good Samaritan Regional Health Center	Mount Vernon	Illinois	United States	62864
52	Edward Hospital Cancer Center	Naperville	Illinois	United States	60540
53	BroMenn Regional Medical Center	Normal	Illinois	United States	61761
54	Community Cancer Center	Normal	Illinois	United States	61761
55	Community Hospital of Ottawa	Ottawa	Illinois	United States	61350
56	Oncology Hematology Associates of Central Illinois, PC - Ottawa	Ottawa	Illinois	United States	61350
57	Cancer Treatment Center at Pekin Hospital	Pekin	Illinois	United States	61554
58	Proctor Hospital	Peoria	Illinois	United States	61614
59	CCOP - Illinois Oncology Research Association	Peoria	Illinois	United States	61615
60	Oncology Hematology Associates of Central Illinois, PC - Peoria	Peoria	Illinois	United States	61615
61	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61636
62	OSF St. Francis Medical Center	Peoria	Illinois	United States	61637
63	Illinois Valley Community Hospital	Peru	Illinois	United States	61354
64	Perry Memorial Hospital	Princeton	Illinois	United States	61356
65	St. Margaret's Hospital	Spring Valley	Illinois	United States	61362
66	Regional Cancer Center at Memorial Medical Center	Springfield	Illinois	United States	62781-0001
67	Carle Cancer Center at Carle Foundation Hospital	Urbana	Illinois	United States	61801
68	CCOP - Carle Cancer Center	Urbana	Illinois	United States	61801
69	St. Francis Hospital and Health Centers - Beech Grove Campus	Beech Grove	Indiana	United States	46107
70	Elkhart General Hospital	Elkhart	Indiana	United States	46515
71	Howard Community Hospital	Kokomo	Indiana	United States	46904
72	Center for Cancer Therapy at LaPorte Hospital and Health Services	La Porte	Indiana	United States	46350
73	Saint Anthony Memorial Health Centers	Michigan City	Indiana	United States	46360
74	Reid Hospital & Health Care Services	Richmond	Indiana	United States	47374
75	CCOP - Northern Indiana CR Consortium	South Bend	Indiana	United States	46601
76	Memorial Hospital of South Bend	South Bend	Indiana	United States	46601
77	Saint Joseph Regional Medical Center	South Bend	Indiana	United States	46617
78	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa	United States	51101
79	Mercy Medical Center - Sioux City	Sioux City	Iowa	United States	51104
80	St. Luke's Regional Medical Center	Sioux City	Iowa	United States	51104
81	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas	United States	66720
82	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas	United States	67801
83	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas	United States	67042
84	Cancer Center of Kansas-Independence	Independence	Kansas	United States	67301
85	Providence Medical Center	Kansas City	Kansas	United States	66112
86	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas	United States	67068
87	Lawrence Memorial Hospital	Lawrence	Kansas	United States	66044
88	Southwest Medical Center	Liberal	Kansas	United States	67901
89	Cancer Center of Kansas, PA - Newton	Newton	Kansas	United States	67114
90	Menorah Medical Center	Overland Park	Kansas	United States	66209
91	Johnson County Radiation Therapy	Overland Park	Kansas	United States	66210
92	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas	United States	67357
93	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas	United States	67124
94	Cancer Center of Kansas, PA - Salina	Salina	Kansas	United States	67042
95	Tammy Walker Cancer Center at Salina Regional Health Center	Salina	Kansas	United States	67401
96	Shawnee Mission Medical Center	Shawnee Mission	Kansas	United States	66204
97	Cotton-O'Neil Cancer Center	Topeka	Kansas	United States	66606
98	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas	United States	67152
99	Associates in Womens Health, PA - North Review	Wichita	Kansas	United States	67208
100	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas	United States	67208
101	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas	United States	67214
102	CCOP - Wichita	Wichita	Kansas	United States	67214
103	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
104	Wesley Medical Center	Wichita	Kansas	United States	67214
105	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas	United States	67156
106	Greenebaum Cancer Center at University of Maryland Medical Center	Baltimore	Maryland	United States	21201
107	Alvin and Lois Lapidus Cancer Institute at Sinai Hospital	Baltimore	Maryland	United States	21215
108	Lahey Clinic Medical Center - Burlington	Burlington	Massachusetts	United States	01805
109	Berkshire Hematology Oncology, PC	Pittsfield	Massachusetts	United States	01201
110	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109-0942
111	Battle Creek Health System Cancer Care Center	Battle Creek	Michigan	United States	49017
112	Bay Regional Medical Center	Bay City	Michigan	United States	48708
113	Mecosta County Medical Center	Big Rapids	Michigan	United States	49307
114	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201-1379
115	Josephine Ford Cancer Center at Henry Ford Hospital	Detroit	Michigan	United States	48202
116	Butterworth Hospital at Spectrum Health	Grand Rapids	Michigan	United States	49503
117	CCOP - Grand Rapids	Grand Rapids	Michigan	United States	49503
118	Lacks Cancer Center at Saint Mary's Health Care	Grand Rapids	Michigan	United States	49503
119	Holland Community Hospital	Holland	Michigan	United States	49423
120	Borgess Medical Center	Kalamazoo	Michigan	United States	49001
121	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007-3731
122	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
123	Hackley Hospital	Muskegon	Michigan	United States	49442
124	Lakeland Regional Cancer Care Center - St. Joseph	Saint Joseph	Michigan	United States	49085
125	Oncology Care Associates, PLLC	Saint Joseph	Michigan	United States	49085
126	Munson Medical Center	Traverse City	Michigan	United States	49684
127	Metro Health Hospital	Wyoming	Michigan	United States	49519
128	University of Mississippi Cancer Clinic	Jackson	Mississippi	United States	39216
129	Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital	Cape Girardeau	Missouri	United States	63701
130	Saint Francis Medical Center	Cape Girardeau	Missouri	United States	63703
131	Saint Luke's Hospital	Chesterfield	Missouri	United States	63017
132	Veterans Affairs Medical Center - Columbia (Truman Memorial)	Columbia	Missouri	United States	65201
133	Ellis Fischel Cancer Center at University of Missouri - Columbia	Columbia	Missouri	United States	65203
134	Independence Regional Health Center	Independence	Missouri	United States	64050
135	Freeman Cancer Institute at Freeman Health System	Joplin	Missouri	United States	64804
136	St. John's Regional Medical Center	Joplin	Missouri	United States	64804
137	Truman Medical Center - Hospital Hill	Kansas City	Missouri	United States	64108
138	Saint Luke's Cancer Institute at Saint Luke's Hospital	Kansas City	Missouri	United States	64111
139	Kansas City Cancer Center at St. Joseph's Medical Mall	Kansas City	Missouri	United States	64114
140	St. Joseph Medical Center	Kansas City	Missouri	United States	64114
141	North Kansas City Hospital	Kansas City	Missouri	United States	64116
142	Parvin Radiation Oncology	Kansas City	Missouri	United States	64116
143	CCOP - Kansas City	Kansas City	Missouri	United States	64131
144	Radiation Oncology Associates of Kansas City at Northland Radiation Oncology Center	Kansas City	Missouri	United States	64154
145	Heartland Regional Medical Center	Saint Joseph	Missouri	United States	64506
146	Midwest Hematology Oncology Group, Incorporated	Saint Louis	Missouri	United States	63109
147	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis	Saint Louis	Missouri	United States	63110
148	CCOP - St. Louis-Cape Girardeau	Saint Louis	Missouri	United States	63141
149	David C. Pratt Cancer Center at St. John's Mercy	Saint Louis	Missouri	United States	63141
150	CCOP - Cancer Research for the Ozarks	Springfield	Missouri	United States	65802
151	St. John's Regional Health Center	Springfield	Missouri	United States	65804
152	Hulston Cancer Center at Cox Medical Center South	Springfield	Missouri	United States	65807
153	CCOP - Montana Cancer Consortium	Billings	Montana	United States	59101
154	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana	United States	59101
155	Northern Rockies Radiation Oncology Center	Billings	Montana	United States	59101
156	St. Vincent Healthcare Cancer Care Services	Billings	Montana	United States	59101
157	Billings Clinic - Downtown	Billings	Montana	United States	59107-7000
158	Bozeman Deaconess Cancer Center	Bozeman	Montana	United States	59715
159	St. James Healthcare Cancer Care	Butte	Montana	United States	59701
160	Big Sky Oncology	Great Falls	Montana	United States	59405-5309
161	Great Falls Clinic - Main Facility	Great Falls	Montana	United States	59405
162	Sletten Cancer Institute at Benefis Healthcare	Great Falls	Montana	United States	59405
163		Great Falls	Montana	United States	59405
164	St. Peter's Hospital	Helena	Montana	United States	59601
165	Glacier Oncology, PLLC	Kalispell	Montana	United States	59901
166	Kalispell Medical Oncology at KRMC	Kalispell	Montana	United States	59901
167	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
168	Community Medical Center	Missoula	Montana	United States	59801
169	Guardian Oncology and Center for Wellness	Missoula	Montana	United States	59804
170	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana	United States	59807-7877
171	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana	United States	59807
172	Good Samaritan Cancer Center at Good Samaritan Hospital	Kearney	Nebraska	United States	68848-1990
173	UNMC Eppley Cancer Center at the University of Nebraska Medical Center	Omaha	Nebraska	United States	68198-6805
174	Roswell Park Cancer Institute	Buffalo	New York	United States	14263-0001
175	Tucker Center for Cancer Care at Orange Regional Medical Center	Middletown	New York	United States	10940-4199
176	New York Weill Cornell Cancer Center at Cornell University	New York	New York	United States	10021
177	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York	United States	14642
178	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill	Chapel Hill	North Carolina	United States	27599-7295
179	Duke Comprehensive Cancer Center	Durham	North Carolina	United States	27710
180	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina	United States	27534
181	McDowell Cancer Center at Akron General Medical Center	Akron	Ohio	United States	44307
182	Mary Rutan Hospital	Bellefontaine	Ohio	United States	43311
183	Adena Regional Medical Center	Chillicothe	Ohio	United States	45601
184	Good Samaritan Hospital Cancer Treatment Center	Cincinnati	Ohio	United States	45220
185	Charles M. Barrett Cancer Center at University Hospital	Cincinnati	Ohio	United States	45267
186	Cleveland Clinic Cancer Center at Fairview Hospital	Cleveland	Ohio	United States	44111
187	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio	United States	44195
188	Riverside Methodist Hospital Cancer Care	Columbus	Ohio	United States	43214-3998
189	CCOP - Columbus	Columbus	Ohio	United States	43215
190	Grant Medical Center Cancer Care	Columbus	Ohio	United States	43215
191	Mount Carmel Health - West Hospital	Columbus	Ohio	United States	43222
192	Doctors Hospital at Ohio Health	Columbus	Ohio	United States	43228
193	Grandview Hospital	Dayton	Ohio	United States	45405
194	Good Samaritan Hospital	Dayton	Ohio	United States	45406
195	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio	United States	45409
196	Samaritan North Cancer Care Center	Dayton	Ohio	United States	45415
197	Veterans Affairs Medical Center - Dayton	Dayton	Ohio	United States	45428
198	CCOP - Dayton	Dayton	Ohio	United States	45429
199	Grady Memorial Hospital	Delaware	Ohio	United States	43015
200	Blanchard Valley Medical Associates	Findlay	Ohio	United States	45840
201	Middletown Regional Hospital	Franklin	Ohio	United States	45005-1066
202	Community Oncology Group at Cleveland Clinic Cancer Center	Independence	Ohio	United States	44131
203	Charles F. Kettering Memorial Hospital	Kettering	Ohio	United States	45429
204	Fairfield Medical Center	Lancaster	Ohio	United States	43130
205	St. Rita's Medical Center	Lima	Ohio	United States	45801
206	Strecker Cancer Center at Marietta Memorial Hospital	Marietta	Ohio	United States	45750
207	Licking Memorial Cancer Care Program at Licking Memorial Hospital	Newark	Ohio	United States	43055
208	Mercy Medical Center	Springfield	Ohio	United States	45504
209	Community Hospital of Springfield and Clark County	Springfield	Ohio	United States	45505
210	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio	United States	45373-1300
211	Mount Carmel St. Ann's Cancer Center	Westerville	Ohio	United States	43081
212	Clinton Memorial Hospital	Wilmington	Ohio	United States	45177
213	Cleveland Clinic - Wooster	Wooster	Ohio	United States	44691
214	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio	United States	45385
215	Genesis - Good Samaritan Hospital	Zanesville	Ohio	United States	43701
216	Legacy Mount Hood Medical Center	Gresham	Oregon	United States	97030
217	Providence Milwaukie Hospital	Milwaukie	Oregon	United States	97222
218	Legacy Good Samaritan Hospital & Comprehensive Cancer Center	Portland	Oregon	United States	97210
219	Providence Cancer Center at Providence Portland Medical Center	Portland	Oregon	United States	97213-2967
220	Adventist Medical Center	Portland	Oregon	United States	97216
221	CCOP - Columbia River Oncology Program	Portland	Oregon	United States	97225
222	Providence St. Vincent Medical Center	Portland	Oregon	United States	97225
223	Legacy Emanuel Hospital and Health Center and Children's Hospital	Portland	Oregon	United States	97227
224	Legacy Meridian Park Hospital	Tualatin	Oregon	United States	97062
225	Roper St. Francis Cancer Center at Roper Hospital	Charleston	South Carolina	United States	29401
226	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina	United States	29425
227	Palmetto Health South Carolina Cancer Center	Columbia	South Carolina	United States	29203
228	CCOP - Greenville	Greenville	South Carolina	United States	29615
229	Joe Arrington Cancer Research and Treatment Center	Lubbock	Texas	United States	79410-1894
230	UMC Southwest Cancer and Research Center	Lubbock	Texas	United States	79415-3364
231	Huntsman Cancer Institute at University of Utah	Salt Lake City	Utah	United States	84112
232	Lynchburg Hematology-Oncology Clinic	Lynchburg	Virginia	United States	24501
233	St. Joseph Cancer Center	Bellingham	Washington	United States	98225
234	Olympic Hematology and Oncology	Bremerton	Washington	United States	98310
235	St. Francis Hospital	Federal Way	Washington	United States	98003
236	Columbia Basin Hematology	Kennewick	Washington	United States	99336
237	Cascade Cancer Center at Evergreen Hospital Medical Center	Kirkland	Washington	United States	98033
238	Olympic Medical Center	Port Angeles	Washington	United States	98362
239	Good Samaritan Cancer Center	Puyallup	Washington	United States	98372
240	Valley Medical Center	Renton	Washington	United States	98055
241	CCOP - Virginia Mason Research Center	Seattle	Washington	United States	98101
242	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98104
243	Harborview Medical Center	Seattle	Washington	United States	98104
244	Minor and James Medical, PLLC	Seattle	Washington	United States	98104
245	Group Health Central Hospital	Seattle	Washington	United States	98112
246	Swedish Cancer Institute at Swedish Medical Center - First Hill Campus	Seattle	Washington	United States	98122-4307
247	Polyclinic First Hill	Seattle	Washington	United States	98122
248	University Cancer Center at University of Washington Medical Center	Seattle	Washington	United States	98195-6043
249	Cancer Care Northwest - Spokane South	Spokane	Washington	United States	99202
250	Franciscan Cancer Center at St. Joseph Medical Center	Tacoma	Washington	United States	98405-3004
251	Allenmore Hospital	Tacoma	Washington	United States	98405
252	CCOP - Northwest	Tacoma	Washington	United States	98405
253	MultiCare Regional Cancer Center at Tacoma General Hospital	Tacoma	Washington	United States	98405
254	St. Clare Hospital	Tacoma	Washington	United States	98499
255	Southwest Washington Medical Center Cancer Center	Vancouver	Washington	United States	98668
256	Wenatchee Valley Medical Center	Wenatchee	Washington	United States	98801-2028
257	North Star Lodge Cancer Center at Yakima Valley Memorial Hospital	Yakima	Washington	United States	98902
258	Schiffler Cancer Center at Wheeling Hospital	Wheeling	West Virginia	United States	26003
259	Welch Cancer Center at Sheridan Memorial Hospital	Sheridan	Wyoming	United States	82801

Sponsors and Collaborators

• Southwest Oncology Group
• National Cancer Institute (NCI)
• Cancer and Leukemia Group B
• Eastern Cooperative Oncology Group

Investigators

• Study Chair: Oliver W. Press, MD, PhD, Fred Hutchinson Cancer Center
• Study Chair: Myron S. Czuczman, MD, Roswell Park Cancer Institute
• Study Chair: Sandra J. Horning, MD, Stanford University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Southwest Oncology Group
• ClinicalTrials.gov Identifier: NCT00006721
• Other Study ID Numbers: CDR0000068321; U10CA032102; S0016; CALGB-50102; S0016
• First Posted: Jan 27, 2003
• Last Update Posted: Sep 24, 2021
• Last Verified: Sep 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Southwest Oncology Group: stage III grade 1 follicular lymphoma; stage III grade 2 follicular lymphoma; stage III grade 3 follicular lymphoma; stage IV grade 1 follicular lymphoma; stage IV grade 2 follicular lymphoma; stage IV grade 3 follicular lymphoma; contiguous stage II grade 1 follicular lymphoma; contiguous stage II grade 2 follicular lymphoma; contiguous stage II grade 3 follicular lymphoma; noncontiguous stage II grade 1 follicular lymphoma; noncontiguous stage II grade 2 follicular lymphoma; noncontiguous stage II grade 3 follicular lymphoma
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Prednisone; Cyclophosphamide; Rituximab; Doxorubicin; Vincristine

Study Results

Participant Flow

Arm/Group Title	CHOP Only	CHOP + Rituximab	CHOP + Tositumomab
Arm/Group Description	Patients receive cyclophosphamide IV over 15 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on day 1. Patients also receive oral prednisone daily on days 1-5. Treatment continues every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. (Arm I closed to accrual as of 12/15/02)	Patients receive cyclophosphamide IV over 15 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on days 8, 29, 50, 71, 92, and 113. Patients also receive oral prednisone daily on days 8-12, 29-33, 50-54, 71-75, 92-96 and 113-117 and rituximab IV over 4-6 hours on days 1, 6, 48, 90, 134, and 141	Patients receive cyclophosphamide IV over 15 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on days 1, 22, 43, 64, 85, and 106. Patients also receive oral prednisone daily on days 1-5, 22-26, 43-47, 64-68, 85-89 and 106-120 and tositumomab (monoclonal antibody anti-B1) IV over 1 hour followed by iodine I 131 tositumomab IV over 20 minutes on days 134 and 141
Period Title: Overall Study
STARTED	17	279	275
Eligible	15	267	265
Eligible and Began Protocol Therapy	14	267	265
COMPLETED	13	254	242
NOT COMPLETED	4	25	33

Baseline Characteristics

Arm/Group Title	CHOP + Rituximab	CHOP + Tositumomab	CHOP Only	Total
Arm/Group Description	Patients receive cyclophosphamide IV over 15 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on days 8, 29, 50, 71, 92, and 113. Patients also receive oral prednisone daily on days 8-12, 29-33, 50-54, 71-75, 92-96 and 113-117 and rituximab IV over 4-6 hours on days 1, 6, 48, 90, 134, and 141	Patients receive cyclophosphamide IV over 15 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on days 1, 22, 43, 64, 85, and 106. Patients also receive oral prednisone daily on days 1-5, 22-26, 43-47, 64-68, 85-89 and 106-120 and tositumomab (monoclonal antibody anti-B1) IV over 1 hour followed by iodine I 131 tositumomab IV over 20 minutes on days 134 and 141	Patients receive cyclophosphamide IV over 15 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on day 1. Patients also receive oral prednisone daily on days 1-5. Treatment continues every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. (Arm I closed to accrual as of 12/15/02)	Total of all reporting groups
Overall Participants	267	265	14	546
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	54.5	53.3	54.5	54
Sex: Female, Male (Count of Participants)
Female	125 46.8%	118 44.5%	4 28.6%	247 45.2%
Male	142 53.2%	147 55.5%	10 71.4%	299 54.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	6 2.2%	10 3.8%	0 0%	16 2.9%
Not Hispanic or Latino	232 86.9%	220 83%	14 100%	466 85.3%
Unknown or Not Reported	29 10.9%	35 13.2%	0 0%	64 11.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.4%	2 0.8%	0 0%	3 0.5%
Asian	5 1.9%	3 1.1%	1 7.1%	9 1.6%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	11 4.1%	10 3.8%	0 0%	21 3.8%
White	241 90.3%	238 89.8%	13 92.9%	492 90.1%
More than one race	1 0.4%	0 0%	0 0%	1 0.2%
Unknown or Not Reported	8 3%	12 4.5%	0 0%	20 3.7%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival at 2 Years
Description	Measured from time of registration to date of of first observation of progression/relapse, or death due to any cause, or last contact date
Time Frame	0-2 years

Outcome Measure Data

Analysis Population Description

All eligible patients who started treatment were included in the analysis. The participants in CHOP alone arm were not assessed due to early closure.

Arm/Group Title	CHOP + Rituximab	CHOP + Tositumomab
Arm/Group Description	Patients receive cyclophosphamide IV over 15 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on days 8, 29, 50, 71, 92, and 113. Patients also receive oral prednisone daily on days 8-12, 29-33, 50-54, 71-75, 92-96 and 113-117 and rituximab IV over 4-6 hours on days 1, 6, 48, 90, 134, and 141	Patients receive cyclophosphamide IV over 15 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on days 1, 22, 43, 64, 85, and 106. Patients also receive oral prednisone daily on days 1-5, 22-26, 43-47, 64-68, 85-89 and 106-120 and tositumomab (monoclonal antibody anti-B1) IV over 1 hour followed by iodine I 131 tositumomab IV over 20 minutes on days 134 and 141
Measure Participants	267	265
Number [percentage of participants]	76 28.5%	80 30.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CHOP + Rituximab, CHOP + Tositumomab
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.11
	Comments
	Method	Regression, Cox
	Comments	adjusting for the stratification factor (serum beta-2 microglobulin level)
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.79
	Confidence Interval	(2-Sided) 95%; 0.6 to 1.05
	Parameter Dispersion	Type: Value:
	Estimation Comments	CHOP + Tositumomab versus CHOP + Rituximab

2. Secondary Outcome

Title	Objective Response (Confirmed and Unconfirmed Complete and Partial Responses)
Description	Complete Response(CR) is a complete disappearance of all disease with the exception of nodes. No new lesions. previously enlarged organs must have regressed and not be palpable. Bone marrow(BM) must be negative if positive at baseline. Normalization of markers. CR Unconfirmed (CRU) does not qualify for CR above, due to a residual nodal mass or an indeterminate BM. Partial Response(PR) is a 50% decrease in the sum of products of greatest diameters (SPD) for up to 6 identified dominant lesions, including spleenic and hepatic nodules from baseline. No new lesions and no increase in the size of liver, spleen or other nodes.
Time Frame	Assessed 200 days and 365 days after initiation of therapy and then every 6 months until death

Outcome Measure Data

Analysis Population Description

All eligible patients who started treatment were included in the analysis. The participants in CHOP alone arm were not assessed due to early closure.

Arm/Group Title	CHOP + Rituximab	CHOP + Tositumomab
Arm/Group Description	Patients receive cyclophosphamide IV over 15 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on days 8, 29, 50, 71, 92, and 113. Patients also receive oral prednisone daily on days 8-12, 29-33, 50-54, 71-75, 92-96 and 113-117 and rituximab IV over 4-6 hours on days 1, 6, 48, 90, 134, and 141	Patients receive cyclophosphamide IV over 15 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on days 1, 22, 43, 64, 85, and 106. Patients also receive oral prednisone daily on days 1-5, 22-26, 43-47, 64-68, 85-89 and 106-120 and tositumomab (monoclonal antibody anti-B1) IV over 1 hour followed by iodine I 131 tositumomab IV over 20 minutes on days 134 and 141
Measure Participants	267	265
Number [participants]	224 83.9%	223 84.2%

3. Secondary Outcome

Title	Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug
Description	Adverse Events (AEs) are reported by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 2.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal
Time Frame	Patients were assessed for adverse events at end of cycle 1-6 of CHOP or R-CHOP, the end of cycle 1-6 of CHOP and once 2 weeks after the completion of I-131 treatment. For either arm, once 3 months after removal from protocol treatment

Outcome Measure Data

Analysis Population Description

Eligible patients who had received any treatment were included in the adverse event summaries. Any CTCAE 2.0 event of Grade 3 (severe), Grade 4 (life threatening), or Grade 5 (fatal) which deemed to be related to protocol treatment are included

Arm/Group Title	CHOP Only	CHOP + Rituximab	CHOP + Tositumomab
Arm/Group Description	Patients receive cyclophosphamide IV over 15 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on day 1. Patients also receive oral prednisone daily on days 1-5. Treatment continues every 21 days for up to 6 courses in the abs ence of disease progression or unacceptable toxicity. (Arm I closed to accrual as of 12/15/02)	Patients receive cyclophosphamide IV over 15 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on days 8, 29, 50, 71, 92, and 113. Patients also receive oral prednisone daily on days 8-12, 29-33, 50-54, 71-75, 92-96 and 113-117 and rituximab IV over 4-6 hours on days 1, 6, 48, 90, 134, and 141	Patients receive cyclophosphamide IV over 15 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on days 1, 22, 43, 64, 85, and 106. Patients also receive oral prednisone daily on days 1-5, 22-26, 43-47, 64-68, 85-89 and 106-120 and tositumomab (monoclonal antibody anti-B1) IV over 1 hour followed by iodine I 131 tositumomab IV over 20 minutes on days 134 and 141
Measure Participants	13	263	263
ARDS	0 0%	0 0%	1 7.1%
Abdominal pain/cramping	0 0%	4 1.5%	3 21.4%
Allergic reaction	0 0%	9 3.4%	1 7.1%
Anemia	0 0%	7 2.6%	8 57.1%
Anorexia	0 0%	3 1.1%	2 14.3%
Anxiety/agitation	0 0%	1 0.4%	3 21.4%
Arrhythmia, NOS	0 0%	1 0.4%	0 0%
Arthralgia	0 0%	3 1.1%	1 7.1%
Arthritis	0 0%	0 0%	1 7.1%
Ascites (non-malignant)	0 0%	0 0%	1 7.1%
Ataxia (incoordination)	0 0%	2 0.8%	1 7.1%
Bone pain	0 0%	2 0.8%	0 0%
Cardiac ischemia/infarction	0 0%	1 0.4%	1 7.1%
Cardiovascular-other	0 0%	1 0.4%	1 7.1%
Cataract	0 0%	1 0.4%	0 0%
Catheter related infection	0 0%	2 0.8%	0 0%
Cerebrovascular ischemia	0 0%	1 0.4%	0 0%
Chest pain,not cardio or pleur	0 0%	4 1.5%	0 0%
Constipation/bowel obstruction	1 0.4%	5 1.9%	4 28.6%
Cough	0 0%	0 0%	1 7.1%
Dehydration	2 0.7%	5 1.9%	1 7.1%
Delusions	0 0%	0 0%	1 7.1%
Depression	0 0%	0 0%	2 14.3%
Diarrhea without colostomy	1 0.4%	3 1.1%	3 21.4%
Dizziness/light headedness	0 0%	0 0%	1 7.1%
Double vision	0 0%	1 0.4%	0 0%
Dyspepsia/heartburn	0 0%	1 0.4%	0 0%
Dyspnea	0 0%	4 1.5%	4 28.6%
Edema	0 0%	0 0%	2 14.3%
Esophagitis/dysphagia	0 0%	1 0.4%	1 7.1%
Fatigue/malaise/lethargy	0 0%	11 4.2%	9 64.3%
Febrile neutropenia	1 0.4%	42 15.8%	26 185.7%
Fever without neutropenia	0 0%	1 0.4%	0 0%
Fever, NOS	0 0%	1 0.4%	0 0%
Flu-like symptoms-other	0 0%	1 0.4%	0 0%
Gastric ulcer	0 0%	0 0%	1 7.1%
Gynecomastia	0 0%	0 0%	1 7.1%
Headache	0 0%	2 0.8%	1 7.1%
Hematologic-other	0 0%	0 0%	3 21.4%
Hyperglycemia	0 0%	10 3.8%	3 21.4%
Hypertension	0 0%	1 0.4%	1 7.1%
Hyperuricemia	0 0%	1 0.4%	0 0%
Hypoalbuminemia	0 0%	1 0.4%	0 0%
Hypokalemia	0 0%	2 0.8%	2 14.3%
Hyponatremia	0 0%	4 1.5%	1 7.1%
Hypophosphatemia	0 0%	1 0.4%	0 0%
Hypotension	0 0%	2 0.8%	1 7.1%
Hypoxia	0 0%	1 0.4%	0 0%
Ileus	0 0%	1 0.4%	0 0%
Infection w/o 3-4 neutropenia	0 0%	4 1.5%	5 35.7%
Infection with 3-4 neutropenia	0 0%	14 5.3%	9 64.3%
Infection, unk ANC	0 0%	4 1.5%	3 21.4%
Insomnia	0 0%	2 0.8%	1 7.1%
Invol. movement/restlessness	0 0%	1 0.4%	0 0%
Joint,muscle,bone-other	0 0%	0 0%	1 7.1%
LVEF decrease/CHF	0 0%	1 0.4%	0 0%
Leukopenia	4 1.5%	104 39.2%	102 728.6%
Lymphopenia	4 1.5%	64 24.2%	68 485.7%
Menses changes	0 0%	2 0.8%	2 14.3%
Muscle weakness (not neuro)	0 0%	2 0.8%	3 21.4%
Myalgia	0 0%	2 0.8%	3 21.4%
Myalgia/arthralgia, NOS	0 0%	2 0.8%	3 21.4%
Nausea	1 0.4%	6 2.3%	10 71.4%
Neuro-other	0 0%	0 0%	2 14.3%
Neuropathic pain	0 0%	1 0.4%	0 0%
Neutropenia/granulocytopenia	8 3%	127 47.9%	136 971.4%
Osteonecrosis	0 0%	0 0%	1 7.1%
PRBC transfusion	0 0%	2 0.8%	5 35.7%
Pain-other	0 0%	2 0.8%	3 21.4%
Pancreatitis	0 0%	1 0.4%	0 0%
Platelet transfusion	0 0%	1 0.4%	7 50%
Pleural effusions	0 0%	2 0.8%	1 7.1%
Pleuritic pain	0 0%	0 0%	1 7.1%
Pneumonitis/infiltrates	0 0%	0 0%	1 7.1%
Pruritus	0 0%	1 0.4%	1 7.1%
Rash/desquamation	0 0%	1 0.4%	2 14.3%
Rectal/perirectal pain	0 0%	0 0%	2 14.3%
Respiratory infect w/ neutrop	0 0%	3 1.1%	5 35.7%
Respiratory infection, unk ANC	0 0%	1 0.4%	2 14.3%
SGOT (AST) increase	0 0%	3 1.1%	0 0%
SGPT (ALT) increase	0 0%	1 0.4%	0 0%
Second primary	0 0%	0 0%	6 42.9%
Seizures	0 0%	1 0.4%	0 0%
Sensory neuropathy	0 0%	10 3.8%	11 78.6%
Sinus tachycardia	0 0%	2 0.8%	0 0%
Skin-other	0 0%	0 0%	1 7.1%
Speech impairment	0 0%	1 0.4%	0 0%
Stomatitis/pharyngitis	0 0%	4 1.5%	2 14.3%
Supraventricular arrhythmia	0 0%	1 0.4%	0 0%
Syncope	0 0%	3 1.1%	1 7.1%
Thrombocytopenia	0 0%	6 2.3%	47 335.7%
Thrombosis/embolism	0 0%	6 2.3%	3 21.4%
Tumor lysis syndrome	0 0%	2 0.8%	0 0%
Urinary frequency/urgency	0 0%	1 0.4%	0 0%
Urinary tr infection, unk ANC	0 0%	1 0.4%	0 0%
Vaginal bleeding	0 0%	0 0%	1 7.1%
Voice change/stridor/larynx	0 0%	0 0%	1 7.1%
Vomiting	1 0.4%	4 1.5%	10 71.4%
Weakness (motor neuropathy)	1 0.4%	4 1.5%	4 28.6%
Weight loss	0 0%	0 0%	2 14.3%

4. Primary Outcome

Title	Progression-free Survival at 5 Years
Description	Measured from time of registration to date of of first observation of progression/relapse, or death due to any cause, or last contact date
Time Frame	0-5 years

Outcome Measure Data

Analysis Population Description

All eligible patients who started treatment were included in the analysis. The participants in CHOP alone arm were not assessed due to early closure.

Arm/Group Title	CHOP + Rituximab	CHOP + Tositumomab
Arm/Group Description	Patients receive cyclophosphamide IV over 15 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on days 8, 29, 50, 71, 92, and 113. Patients also receive oral prednisone daily on days 8-12, 29-33, 50-54, 71-75, 92-96 and 113-117 and rituximab IV over 4-6 hours on days 1, 6, 48, 90, 134, and 141	Patients receive cyclophosphamide IV over 15 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on days 1, 22, 43, 64, 85, and 106. Patients also receive oral prednisone daily on days 1-5, 22-26, 43-47, 64-68, 85-89 and 106-120 and tositumomab (monoclonal antibody anti-B1) IV over 1 hour followed by iodine I 131 tositumomab IV over 20 minutes on days 134 and 141
Measure Participants	267	265
Number [percentage of participants]	60 22.5%	66 24.9%

5. Primary Outcome

Title	Overall Survival at 2 Years
Description	Measured from date of registration to date of death due to any cause
Time Frame	0-2 years

Outcome Measure Data

Analysis Population Description

All eligible patients who started treatment were included in the analysis. The participants in CHOP alone arm were not assessed due to early closure.

Arm/Group Title	CHOP + Rituximab	CHOP + Tositumomab
Arm/Group Description	Patients receive cyclophosphamide IV over 15 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on days 8, 29, 50, 71, 92, and 113. Patients also receive oral prednisone daily on days 8-12, 29-33, 50-54, 71-75, 92-96 and 113-117 and rituximab IV over 4-6 hours on days 1, 6, 48, 90, 134, and 141	Patients receive cyclophosphamide IV over 15 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on days 1, 22, 43, 64, 85, and 106. Patients also receive oral prednisone daily on days 1-5, 22-26, 43-47, 64-68, 85-89 and 106-120 and tositumomab (monoclonal antibody anti-B1) IV over 1 hour followed by iodine I 131 tositumomab IV over 20 minutes on days 134 and 141
Measure Participants	267	265
Number [percentage of participants]	97 36.3%	93 35.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CHOP + Rituximab, CHOP + Tositumomab
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.08
	Comments
	Method	Regression, Cox
	Comments	adjusting for the stratification factor (serum beta-2 microglobulin level)
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.55
	Confidence Interval	(2-Sided) 95%; 0.95 to 2.54
	Parameter Dispersion	Type: Value:
	Estimation Comments	CHOP + Tositumomab versus CHOP + Rituximab

6. Primary Outcome

Title	Overall Survival at 5 Years
Description	Measured from date of registration to date of death due to any cause
Time Frame	0-5 years

Outcome Measure Data

Analysis Population Description

All eligible patients who started treatment were included in the analysis. The participants in CHOP alone arm were not assessed due to early closure.

Arm/Group Title	CHOP + Rituximab	CHOP + Tositumomab
Arm/Group Description	Patients receive cyclophosphamide IV over 15 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on days 8, 29, 50, 71, 92, and 113. Patients also receive oral prednisone daily on days 8-12, 29-33, 50-54, 71-75, 92-96 and 113-117 and rituximab IV over 4-6 hours on days 1, 6, 48, 90, 134, and 141	Patients receive cyclophosphamide IV over 15 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on days 1, 22, 43, 64, 85, and 106. Patients also receive oral prednisone daily on days 1-5, 22-26, 43-47, 64-68, 85-89 and 106-120 and tositumomab (monoclonal antibody anti-B1) IV over 1 hour followed by iodine I 131 tositumomab IV over 20 minutes on days 134 and 141
Measure Participants	267	265
Number [percentage of participants]	92 34.5%	86 32.5%

Adverse Events

Time Frame	Patients were assessed for adverse events at end of cycle 1-6 of CHOP or R-CHOP, the end of cycle 1-6 of CHOP and once 2 weeks after the completion of I-131 treatment. For either arm, once 3 months after removal from protocol treatment
Arm/Group Title	CHOP Only		CHOP + Rituximab		CHOP + Tositumomab
Arm/Group Description	Patients receive cyclophosphamide IV over 15 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on day 1. Patients also receive oral prednisone daily on days 1-5. Treatment continues every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. (Arm I closed to accrual as of 12/15/02)		Patients receive cyclophosphamide IV over 15 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on days 8, 29, 50, 71, 92, and 113. Patients also receive oral prednisone daily on days 8-12, 29-33, 50-54, 71-75, 92-96 and 113-117 and rituximab IV over 4-6 hours on days 1, 6, 48, 90, 134, and 141		Patients receive cyclophosphamide IV over 15 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on days 1, 22, 43, 64, 85, and 106. Patients also receive oral prednisone daily on days 1-5, 22-26, 43-47, 64-68, 85-89 and 106-120 and tositumomab (monoclonal antibody anti-B1) IV over 1 hour followed by iodine I 131 tositumomab IV over 20 minutes on days 134 and 141
All Cause Mortality
	CHOP Only		CHOP + Rituximab		CHOP + Tositumomab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	CHOP Only		CHOP + Rituximab		CHOP + Tositumomab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/13 (0%)		3/263 (1.1%)		16/263 (6.1%)
Blood and lymphatic system disorders
Febrile neutropenia	0/13 (0%)		0/263 (0%)		2/263 (0.8%)
Hematologic-other	0/13 (0%)		0/263 (0%)		3/263 (1.1%)
Platelet transfusion	0/13 (0%)		0/263 (0%)		1/263 (0.4%)
Cardiac disorders
LVEF decrease/CHF	0/13 (0%)		0/263 (0%)		1/263 (0.4%)
Gastrointestinal disorders
Pancreatitis	0/13 (0%)		1/263 (0.4%)		0/263 (0%)
Infections and infestations
Infection w/o 3-4 neutropenia	0/13 (0%)		0/263 (0%)		2/263 (0.8%)
Respiratory infect w/ neutrop	0/13 (0%)		0/263 (0%)		1/263 (0.4%)
Investigations
Neutropenia/granulocytopenia	0/13 (0%)		0/263 (0%)		1/263 (0.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Second primary	0/13 (0%)		0/263 (0%)		6/263 (2.3%)
Nervous system disorders
Cerebrovascular ischemia	0/13 (0%)		1/263 (0.4%)		0/263 (0%)
Respiratory, thoracic and mediastinal disorders
ARDS	0/13 (0%)		0/263 (0%)		1/263 (0.4%)
Vascular disorders
Thrombosis/embolism	0/13 (0%)		1/263 (0.4%)		0/263 (0%)
Other (Not Including Serious) Adverse Events
	CHOP Only		CHOP + Rituximab		CHOP + Tositumomab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/13 (100%)		262/263 (99.6%)		261/263 (99.2%)
Blood and lymphatic system disorders
Anemia	5/13 (38.5%)		177/263 (67.3%)		192/263 (73%)
Febrile neutropenia	1/13 (7.7%)		42/263 (16%)		24/263 (9.1%)
Cardiac disorders
Sinus tachycardia	1/13 (7.7%)		0/263 (0%)		0/263 (0%)
Endocrine disorders
Hypothyroidism	1/13 (7.7%)		0/263 (0%)		0/263 (0%)
Gastrointestinal disorders
Abdominal pain/cramping	2/13 (15.4%)		61/263 (23.2%)		47/263 (17.9%)
Constipation/bowel obstruction	4/13 (30.8%)		106/263 (40.3%)		99/263 (37.6%)
Diarrhea without colostomy	3/13 (23.1%)		57/263 (21.7%)		61/263 (23.2%)
Dyspepsia/heartburn	0/13 (0%)		38/263 (14.4%)		40/263 (15.2%)
Esophagitis/dysphagia	1/13 (7.7%)		17/263 (6.5%)		0/263 (0%)
GI-other	0/13 (0%)		16/263 (6.1%)		0/263 (0%)
Nausea	6/13 (46.2%)		149/263 (56.7%)		173/263 (65.8%)
Stomatitis/pharyngitis	5/13 (38.5%)		90/263 (34.2%)		84/263 (31.9%)
Vomiting	5/13 (38.5%)		56/263 (21.3%)		83/263 (31.6%)
General disorders
Edema	2/13 (15.4%)		45/263 (17.1%)		33/263 (12.5%)
Fatigue/malaise/lethargy	7/13 (53.8%)		207/263 (78.7%)		198/263 (75.3%)
Fever without neutropenia	0/13 (0%)		35/263 (13.3%)		24/263 (9.1%)
Fever, NOS	1/13 (7.7%)		0/263 (0%)		0/263 (0%)
Pain-other	0/13 (0%)		57/263 (21.7%)		42/263 (16%)
Rigors/chills	2/13 (15.4%)		65/263 (24.7%)		29/263 (11%)
Sweating	0/13 (0%)		56/263 (21.3%)		33/263 (12.5%)
Immune system disorders
Allergic reaction	1/13 (7.7%)		49/263 (18.6%)		0/263 (0%)
Infections and infestations
Infection w/o 3-4 neutropenia	0/13 (0%)		42/263 (16%)		39/263 (14.8%)
Infection with 3-4 neutropenia	0/13 (0%)		17/263 (6.5%)		0/263 (0%)
Respiratory infect w/o neutrop	0/13 (0%)		15/263 (5.7%)		14/263 (5.3%)
Investigations
Alkaline phosphatase increase	0/13 (0%)		22/263 (8.4%)		15/263 (5.7%)
Creatinine increase	0/13 (0%)		17/263 (6.5%)		15/263 (5.7%)
Leukopenia	11/13 (84.6%)		187/263 (71.1%)		205/263 (77.9%)
Lymphopenia	7/13 (53.8%)		145/263 (55.1%)		155/263 (58.9%)
Neutropenia/granulocytopenia	10/13 (76.9%)		174/263 (66.2%)		187/263 (71.1%)
SGOT (AST) increase	2/13 (15.4%)		41/263 (15.6%)		45/263 (17.1%)
SGPT (ALT) increase	0/13 (0%)		26/263 (9.9%)		41/263 (15.6%)
Thrombocytopenia	3/13 (23.1%)		77/263 (29.3%)		140/263 (53.2%)
Weight loss	0/13 (0%)		26/263 (9.9%)		31/263 (11.8%)
Metabolism and nutrition disorders
Anorexia	3/13 (23.1%)		63/263 (24%)		59/263 (22.4%)
Dehydration	2/13 (15.4%)		21/263 (8%)		0/263 (0%)
Hypercalcemia	1/13 (7.7%)		0/263 (0%)		0/263 (0%)
Hyperglycemia	2/13 (15.4%)		79/263 (30%)		77/263 (29.3%)
Hypernatremia	1/13 (7.7%)		0/263 (0%)		0/263 (0%)
Hypoalbuminemia	0/13 (0%)		22/263 (8.4%)		15/263 (5.7%)
Hypocalcemia	1/13 (7.7%)		24/263 (9.1%)		15/263 (5.7%)
Hypoglycemia	0/13 (0%)		0/263 (0%)		15/263 (5.7%)
Hypokalemia	0/13 (0%)		16/263 (6.1%)		0/263 (0%)
Hyponatremia	0/13 (0%)		22/263 (8.4%)		0/263 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/13 (0%)		37/263 (14.1%)		41/263 (15.6%)
Bone pain	1/13 (7.7%)		16/263 (6.1%)		0/263 (0%)
Chest pain,not cardio or pleur	0/13 (0%)		20/263 (7.6%)		0/263 (0%)
Joint,muscle,bone-other	0/13 (0%)		14/263 (5.3%)		17/263 (6.5%)
Myalgia	1/13 (7.7%)		63/263 (24%)		57/263 (21.7%)
Myalgia/arthralgia, NOS	0/13 (0%)		25/263 (9.5%)		40/263 (15.2%)
Nervous system disorders
Dizziness/light headedness	1/13 (7.7%)		22/263 (8.4%)		20/263 (7.6%)
Headache	3/13 (23.1%)		61/263 (23.2%)		52/263 (19.8%)
Sensory neuropathy	7/13 (53.8%)		120/263 (45.6%)		119/263 (45.2%)
Taste disturbance	0/13 (0%)		29/263 (11%)		30/263 (11.4%)
Weakness (motor neuropathy)	2/13 (15.4%)		27/263 (10.3%)		22/263 (8.4%)
Psychiatric disorders
Anxiety/agitation	1/13 (7.7%)		34/263 (12.9%)		38/263 (14.4%)
Depression	2/13 (15.4%)		20/263 (7.6%)		31/263 (11.8%)
Insomnia	2/13 (15.4%)		60/263 (22.8%)		59/263 (22.4%)
Renal and urinary disorders
Urinary frequency/urgency	0/13 (0%)		16/263 (6.1%)		21/263 (8%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	1/13 (7.7%)		23/263 (8.7%)		21/263 (8%)
Cough	1/13 (7.7%)		71/263 (27%)		43/263 (16.3%)
Dyspnea	2/13 (15.4%)		52/263 (19.8%)		44/263 (16.7%)
Hiccoughs	2/13 (15.4%)		0/263 (0%)		0/263 (0%)
Skin and subcutaneous tissue disorders
Alopecia	11/13 (84.6%)		176/263 (66.9%)		151/263 (57.4%)
Nail changes	1/13 (7.7%)		0/263 (0%)		0/263 (0%)
Pigmentation changes/yellowing	1/13 (7.7%)		0/263 (0%)		0/263 (0%)
Pruritus	0/13 (0%)		17/263 (6.5%)		16/263 (6.1%)
Rash/desquamation	2/13 (15.4%)		37/263 (14.1%)		44/263 (16.7%)
Skin-other	0/13 (0%)		0/263 (0%)		16/263 (6.1%)
Vascular disorders
Flushing	1/13 (7.7%)		0/263 (0%)		0/263 (0%)
Hot flashes	0/13 (0%)		14/263 (5.3%)		0/263 (0%)
Hypotension	1/13 (7.7%)		16/263 (6.1%)		0/263 (0%)

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.