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

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ClinicalTrials.gov Identifier: NCT00006721

Recruitment Status : Active, not recruiting

First Posted : January 27, 2003

Results First Posted : February 26, 2013

Last Update Posted : September 26, 2023

View this study on the modernized ClinicalTrials.gov

Sponsor:

Collaborators:

National Cancer Institute (NCI)

Cancer and Leukemia Group B

Eastern Cooperative Oncology Group

Information provided by (Responsible Party):

SWOG Cancer Research Network

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition	Lymphoma
Interventions	Biological: rituximab Drug: cyclophosphamide Drug: doxorubicin Drug: prednisone Drug: vincristine Radiation: tositumomab
Enrollment	571

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	CHOP Only	CHOP + Rituximab	CHOP + Tositumomab
Arm/Group Description	Patients receive cyclophosphamide I...	Patients receive cyclophosphamide I...	Patients receive cyclophosphamide I...
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
Reason Not Completed
Adverse Event	0	4	4
Refusal Unrelated to Adverse Event	1	0	8
Progression/Relapse	0	1	2
Death	0	1	2
Other - Not Protocol Specified	0	7	7
Ineligible	2	12	10
Eligible but no Treatment Received	1	0	0

Baseline Characteristics

Arm/Group Title		CHOP + Rituximab	CHOP + Tositumomab	CHOP Only	Total
Arm/Group Description		Patients receive cyclophosphamide I...	Patients receive cyclophosphamide I...	Patients receive cyclophosphamide I...	Total of all reporting groups
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 Number of Baseline Participants		267	265	14	546
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Median (Full Range) Unit of measure: Years
	Number Analyzed	267 participants	265 participants	14 participants	546 participants
		54.5 (23.5 to 86.9)	53.3 (23.6 to 81.8)	54.5 (32.6 to 75.5)	54 (23.5 to 86.9)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	267 participants	265 participants	14 participants	546 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) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	267 participants	265 participants	14 participants	546 participants
	Hispanic or Latino	6 2.2%	10 3.8%	0 0.0%	16 2.9%
	Not Hispanic or Latino	232 86.9%	220 83.0%	14 100.0%	466 85.3%
	Unknown or Not Reported	29 10.9%	35 13.2%	0 0.0%	64 11.7%
Race (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	267 participants	265 participants	14 participants	546 participants
	American Indian or Alaska Native	1 0.4%	2 0.8%	0 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 0.0%	0 0.0%
	Black or African American	11 4.1%	10 3.8%	0 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 0.0%	1 0.2%
	Unknown or Not Reported	8 3.0%	12 4.5%	0 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 ...
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 I...	Patients receive cyclophosphamide I...
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
Overall Number of Participants Analyzed	267	265
Measure Type: Number Unit of Measure: percentage of participants
	76	80

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CHOP + Rituximab, CHOP + Tositumomab
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.11
	Comments	[Not Specified]
	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
	Estimation Comments	CHOP + Tositumomab versus CHOP + Rituximab

2.Primary Outcome


Title	Progression-free Survival at 5 Years
Description	Measured from time of registration to date of of first observation of ...
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 I...	Patients receive cyclophosphamide I...
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
Overall Number of Participants Analyzed	267	265
Measure Type: Number Unit of Measure: percentage of participants
	60	66

3.Primary Outcome


Title	Overall Survival at 2 Years
Description	Measured from date of registration to date of death due to any cause
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 I...	Patients receive cyclophosphamide I...
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
Overall Number of Participants Analyzed	267	265
Measure Type: Number Unit of Measure: percentage of participants
	97	93

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CHOP + Rituximab, CHOP + Tositumomab
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.08
	Comments	[Not Specified]
	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
	Estimation Comments	CHOP + Tositumomab versus CHOP + Rituximab

4.Primary Outcome


Title	Overall Survival at 5 Years
Description	Measured from date of registration to date of death due to any cause
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 I...	Patients receive cyclophosphamide I...
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
Overall Number of Participants Analyzed	267	265
Measure Type: Number Unit of Measure: percentage of participants
	92	86

5.Secondary Outcome


Title	Objective Response (Confirmed and Unconfirmed Complete and Partial Responses)
Description	Complete Response(CR) is a complete disappearance of all disease with ...
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 I...	Patients receive cyclophosphamide I...
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
Overall Number of Participants Analyzed	267	265
Measure Type: Number Unit of Measure: participants
	224	223

6.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 Criter...
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 I...	Patients receive cyclophosphamide I...	Patients receive cyclophosphamide I...
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
Overall Number of Participants Analyzed	13	263	263
Measure Type: Number Unit of Measure: Participants
ARDS	0	0	1
Abdominal pain/cramping	0	4	3
Allergic reaction	0	9	1
Anemia	0	7	8
Anorexia	0	3	2
Anxiety/agitation	0	1	3
Arrhythmia, NOS	0	1	0
Arthralgia	0	3	1
Arthritis	0	0	1
Ascites (non-malignant)	0	0	1
Ataxia (incoordination)	0	2	1
Bone pain	0	2	0
Cardiac ischemia/infarction	0	1	1
Cardiovascular-other	0	1	1
Cataract	0	1	0
Catheter related infection	0	2	0
Cerebrovascular ischemia	0	1	0
Chest pain,not cardio or pleur	0	4	0
Constipation/bowel obstruction	1	5	4
Cough	0	0	1
Dehydration	2	5	1
Delusions	0	0	1
Depression	0	0	2
Diarrhea without colostomy	1	3	3
Dizziness/light headedness	0	0	1
Double vision	0	1	0
Dyspepsia/heartburn	0	1	0
Dyspnea	0	4	4
Edema	0	0	2
Esophagitis/dysphagia	0	1	1
Fatigue/malaise/lethargy	0	11	9
Febrile neutropenia	1	42	26
Fever without neutropenia	0	1	0
Fever, NOS	0	1	0
Flu-like symptoms-other	0	1	0
Gastric ulcer	0	0	1
Gynecomastia	0	0	1
Headache	0	2	1
Hematologic-other	0	0	3
Hyperglycemia	0	10	3
Hypertension	0	1	1
Hyperuricemia	0	1	0
Hypoalbuminemia	0	1	0
Hypokalemia	0	2	2
Hyponatremia	0	4	1
Hypophosphatemia	0	1	0
Hypotension	0	2	1
Hypoxia	0	1	0
Ileus	0	1	0
Infection w/o 3-4 neutropenia	0	4	5
Infection with 3-4 neutropenia	0	14	9
Infection, unk ANC	0	4	3
Insomnia	0	2	1
Invol. movement/restlessness	0	1	0
Joint,muscle,bone-other	0	0	1
LVEF decrease/CHF	0	1	0
Leukopenia	4	104	102
Lymphopenia	4	64	68
Menses changes	0	2	2
Muscle weakness (not neuro)	0	2	3
Myalgia	0	2	3
Myalgia/arthralgia, NOS	0	2	3
Nausea	1	6	10
Neuro-other	0	0	2
Neuropathic pain	0	1	0
Neutropenia/granulocytopenia	8	127	136
Osteonecrosis	0	0	1
PRBC transfusion	0	2	5
Pain-other	0	2	3
Pancreatitis	0	1	0
Platelet transfusion	0	1	7
Pleural effusions	0	2	1
Pleuritic pain	0	0	1
Pneumonitis/infiltrates	0	0	1
Pruritus	0	1	1
Rash/desquamation	0	1	2
Rectal/perirectal pain	0	0	2
Respiratory infect w/ neutrop	0	3	5
Respiratory infection, unk ANC	0	1	2
SGOT (AST) increase	0	3	0
SGPT (ALT) increase	0	1	0
Second primary	0	0	6
Seizures	0	1	0
Sensory neuropathy	0	10	11
Sinus tachycardia	0	2	0
Skin-other	0	0	1
Speech impairment	0	1	0
Stomatitis/pharyngitis	0	4	2
Supraventricular arrhythmia	0	1	0
Syncope	0	3	1
Thrombocytopenia	0	6	47
Thrombosis/embolism	0	6	3
Tumor lysis syndrome	0	2	0
Urinary frequency/urgency	0	1	0
Urinary tr infection, unk ANC	0	1	0
Vaginal bleeding	0	0	1
Voice change/stridor/larynx	0	0	1
Vomiting	1	4	10
Weakness (motor neuropathy)	1	4	4
Weight loss	0	0	2

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
Adverse Event Reporting Description	[Not Specified]

Arm/Group Title	CHOP Only	CHOP + Rituximab	CHOP + Tositumomab
Arm/Group Description	Patients receive cyclophosphamide I...	Patients receive cyclophosphamide I...	Patients receive cyclophosphamide I...
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 (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--	--/--
Serious Adverse Events Serious Adverse Events
	CHOP Only	CHOP + Rituximab	CHOP + Tositumomab
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/13 (0.00%)	3/263 (1.14%)	16/263 (6.08%)
Blood and lymphatic system disorders
Febrile neutropenia ^† 1	0/13 (0.00%)	0/263 (0.00%)	2/263 (0.76%)
Hematologic-other ^† 1	0/13 (0.00%)	0/263 (0.00%)	3/263 (1.14%)
Platelet transfusion ^† 1	0/13 (0.00%)	0/263 (0.00%)	1/263 (0.38%)
Cardiac disorders
LVEF decrease/CHF ^† 1	0/13 (0.00%)	0/263 (0.00%)	1/263 (0.38%)
Gastrointestinal disorders
Pancreatitis ^† 1	0/13 (0.00%)	1/263 (0.38%)	0/263 (0.00%)
Infections and infestations
Infection w/o 3-4 neutropenia ^† 1	0/13 (0.00%)	0/263 (0.00%)	2/263 (0.76%)
Respiratory infect w/ neutrop ^† 1	0/13 (0.00%)	0/263 (0.00%)	1/263 (0.38%)
Investigations
Neutropenia/granulocytopenia ^† 1	0/13 (0.00%)	0/263 (0.00%)	1/263 (0.38%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Second primary ^† 1	0/13 (0.00%)	0/263 (0.00%)	6/263 (2.28%)
Nervous system disorders
Cerebrovascular ischemia ^† 1	0/13 (0.00%)	1/263 (0.38%)	0/263 (0.00%)
Respiratory, thoracic and mediastinal disorders
ARDS ^† 1	0/13 (0.00%)	0/263 (0.00%)	1/263 (0.38%)
Vascular disorders
Thrombosis/embolism ^† 1	0/13 (0.00%)	1/263 (0.38%)	0/263 (0.00%)
† Indicates events were collected by systematic assessment 1 Term from vocabulary, CTCAE (2.0)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	CHOP Only	CHOP + Rituximab	CHOP + Tositumomab
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	13/13 (100.00%)	262/263 (99.62%)	261/263 (99.24%)
Blood and lymphatic system disorders
Anemia ^† 1	5/13 (38.46%)	177/263 (67.30%)	192/263 (73.00%)
Febrile neutropenia ^† 1	1/13 (7.69%)	42/263 (15.97%)	24/263 (9.13%)
Cardiac disorders
Sinus tachycardia ^† 1	1/13 (7.69%)	0/263 (0.00%)	0/263 (0.00%)
Endocrine disorders
Hypothyroidism ^† 1	1/13 (7.69%)	0/263 (0.00%)	0/263 (0.00%)
Gastrointestinal disorders
Abdominal pain/cramping ^† 1	2/13 (15.38%)	61/263 (23.19%)	47/263 (17.87%)
Constipation/bowel obstruction ^† 1	4/13 (30.77%)	106/263 (40.30%)	99/263 (37.64%)
Diarrhea without colostomy ^† 1	3/13 (23.08%)	57/263 (21.67%)	61/263 (23.19%)
Dyspepsia/heartburn ^† 1	0/13 (0.00%)	38/263 (14.45%)	40/263 (15.21%)
Esophagitis/dysphagia ^† 1	1/13 (7.69%)	17/263 (6.46%)	0/263 (0.00%)
GI-other ^† 1	0/13 (0.00%)	16/263 (6.08%)	0/263 (0.00%)
Nausea ^† 1	6/13 (46.15%)	149/263 (56.65%)	173/263 (65.78%)
Stomatitis/pharyngitis ^† 1	5/13 (38.46%)	90/263 (34.22%)	84/263 (31.94%)
Vomiting ^† 1	5/13 (38.46%)	56/263 (21.29%)	83/263 (31.56%)
General disorders
Edema ^† 1	2/13 (15.38%)	45/263 (17.11%)	33/263 (12.55%)
Fatigue/malaise/lethargy ^† 1	7/13 (53.85%)	207/263 (78.71%)	198/263 (75.29%)
Fever without neutropenia ^† 1	0/13 (0.00%)	35/263 (13.31%)	24/263 (9.13%)
Fever, NOS ^† 1	1/13 (7.69%)	0/263 (0.00%)	0/263 (0.00%)
Pain-other ^† 1	0/13 (0.00%)	57/263 (21.67%)	42/263 (15.97%)
Rigors/chills ^† 1	2/13 (15.38%)	65/263 (24.71%)	29/263 (11.03%)
Sweating ^† 1	0/13 (0.00%)	56/263 (21.29%)	33/263 (12.55%)
Immune system disorders
Allergic reaction ^† 1	1/13 (7.69%)	49/263 (18.63%)	0/263 (0.00%)
Infections and infestations
Infection w/o 3-4 neutropenia ^† 1	0/13 (0.00%)	42/263 (15.97%)	39/263 (14.83%)
Infection with 3-4 neutropenia ^† 1	0/13 (0.00%)	17/263 (6.46%)	0/263 (0.00%)
Respiratory infect w/o neutrop ^† 1	0/13 (0.00%)	15/263 (5.70%)	14/263 (5.32%)
Investigations
Alkaline phosphatase increase ^† 1	0/13 (0.00%)	22/263 (8.37%)	15/263 (5.70%)
Creatinine increase ^† 1	0/13 (0.00%)	17/263 (6.46%)	15/263 (5.70%)
Leukopenia ^† 1	11/13 (84.62%)	187/263 (71.10%)	205/263 (77.95%)
Lymphopenia ^† 1	7/13 (53.85%)	145/263 (55.13%)	155/263 (58.94%)
Neutropenia/granulocytopenia ^† 1	10/13 (76.92%)	174/263 (66.16%)	187/263 (71.10%)
SGOT (AST) increase ^† 1	2/13 (15.38%)	41/263 (15.59%)	45/263 (17.11%)
SGPT (ALT) increase ^† 1	0/13 (0.00%)	26/263 (9.89%)	41/263 (15.59%)
Thrombocytopenia ^† 1	3/13 (23.08%)	77/263 (29.28%)	140/263 (53.23%)
Weight loss ^† 1	0/13 (0.00%)	26/263 (9.89%)	31/263 (11.79%)
Metabolism and nutrition disorders
Anorexia ^† 1	3/13 (23.08%)	63/263 (23.95%)	59/263 (22.43%)
Dehydration ^† 1	2/13 (15.38%)	21/263 (7.98%)	0/263 (0.00%)
Hypercalcemia ^† 1	1/13 (7.69%)	0/263 (0.00%)	0/263 (0.00%)
Hyperglycemia ^† 1	2/13 (15.38%)	79/263 (30.04%)	77/263 (29.28%)
Hypernatremia ^† 1	1/13 (7.69%)	0/263 (0.00%)	0/263 (0.00%)
Hypoalbuminemia ^† 1	0/13 (0.00%)	22/263 (8.37%)	15/263 (5.70%)
Hypocalcemia ^† 1	1/13 (7.69%)	24/263 (9.13%)	15/263 (5.70%)
Hypoglycemia ^† 1	0/13 (0.00%)	0/263 (0.00%)	15/263 (5.70%)
Hypokalemia ^† 1	0/13 (0.00%)	16/263 (6.08%)	0/263 (0.00%)
Hyponatremia ^† 1	0/13 (0.00%)	22/263 (8.37%)	0/263 (0.00%)
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	0/13 (0.00%)	37/263 (14.07%)	41/263 (15.59%)
Bone pain ^† 1	1/13 (7.69%)	16/263 (6.08%)	0/263 (0.00%)
Chest pain,not cardio or pleur ^† 1	0/13 (0.00%)	20/263 (7.60%)	0/263 (0.00%)
Joint,muscle,bone-other ^† 1	0/13 (0.00%)	14/263 (5.32%)	17/263 (6.46%)
Myalgia ^† 1	1/13 (7.69%)	63/263 (23.95%)	57/263 (21.67%)
Myalgia/arthralgia, NOS ^† 1	0/13 (0.00%)	25/263 (9.51%)	40/263 (15.21%)
Nervous system disorders
Dizziness/light headedness ^† 1	1/13 (7.69%)	22/263 (8.37%)	20/263 (7.60%)
Headache ^† 1	3/13 (23.08%)	61/263 (23.19%)	52/263 (19.77%)
Sensory neuropathy ^† 1	7/13 (53.85%)	120/263 (45.63%)	119/263 (45.25%)
Taste disturbance ^† 1	0/13 (0.00%)	29/263 (11.03%)	30/263 (11.41%)
Weakness (motor neuropathy) ^† 1	2/13 (15.38%)	27/263 (10.27%)	22/263 (8.37%)
Psychiatric disorders
Anxiety/agitation ^† 1	1/13 (7.69%)	34/263 (12.93%)	38/263 (14.45%)
Depression ^† 1	2/13 (15.38%)	20/263 (7.60%)	31/263 (11.79%)
Insomnia ^† 1	2/13 (15.38%)	60/263 (22.81%)	59/263 (22.43%)
Renal and urinary disorders
Urinary frequency/urgency ^† 1	0/13 (0.00%)	16/263 (6.08%)	21/263 (7.98%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis ^† 1	1/13 (7.69%)	23/263 (8.75%)	21/263 (7.98%)
Cough ^† 1	1/13 (7.69%)	71/263 (27.00%)	43/263 (16.35%)
Dyspnea ^† 1	2/13 (15.38%)	52/263 (19.77%)	44/263 (16.73%)
Hiccoughs ^† 1	2/13 (15.38%)	0/263 (0.00%)	0/263 (0.00%)
Skin and subcutaneous tissue disorders
Alopecia ^† 1	11/13 (84.62%)	176/263 (66.92%)	151/263 (57.41%)
Nail changes ^† 1	1/13 (7.69%)	0/263 (0.00%)	0/263 (0.00%)
Pigmentation changes/yellowing ^† 1	1/13 (7.69%)	0/263 (0.00%)	0/263 (0.00%)
Pruritus ^† 1	0/13 (0.00%)	17/263 (6.46%)	16/263 (6.08%)
Rash/desquamation ^† 1	2/13 (15.38%)	37/263 (14.07%)	44/263 (16.73%)
Skin-other ^† 1	0/13 (0.00%)	0/263 (0.00%)	16/263 (6.08%)
Vascular disorders
Flushing ^† 1	1/13 (7.69%)	0/263 (0.00%)	0/263 (0.00%)
Hot flashes ^† 1	0/13 (0.00%)	14/263 (5.32%)	0/263 (0.00%)
Hypotension ^† 1	1/13 (7.69%)	16/263 (6.08%)	0/263 (0.00%)
† Indicates events were collected by systematic assessment 1 Term from vocabulary, CTCAE (2.0)

Limitations and 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.

Results Point of Contact

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Name/Title:	Study Statistician
Organization:	SWOG Statistical Center
Phone:	206-667-4623

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Shadman M, Li H, Rimsza L, Leonard JP, Kaminski MS, Braziel RM, Spier CM, Gopal AK, Maloney DG, Cheson BD, Dakhil S, LeBlanc M, Smith SM, Fisher RI, Friedberg JW, Press OW. Continued Excellent Outcomes in Previously Untreated Patients With Follicular Lymphoma After Treatment With CHOP Plus Rituximab or CHOP Plus 131I-Tositumomab: Long-Term Follow-Up of Phase III Randomized Study SWOG-S0016. J Clin Oncol. 2018 Mar 1;36(7):697-703. doi: 10.1200/JCO.2017.74.5083. Epub 2018 Jan 22.

Press OW, Unger JM, Rimsza LM, Friedberg JW, LeBlanc M, Czuczman MS, Kaminski M, Braziel RM, Spier C, Gopal AK, Maloney DG, Cheson BD, Dakhil SR, Miller TP, Fisher RI. Phase III randomized intergroup trial of CHOP plus rituximab compared with CHOP chemotherapy plus (131)iodine-tositumomab for previously untreated follicular non-Hodgkin lymphoma: SWOG S0016. J Clin Oncol. 2013 Jan 20;31(3):314-20. doi: 10.1200/JCO.2012.42.4101. Epub 2012 Dec 10.

Layout table for additonal information

Responsible Party:	SWOG Cancer Research Network
ClinicalTrials.gov Identifier:	NCT00006721
Other Study ID Numbers:	CDR0000068321 U10CA032102 ( U.S. NIH Grant/Contract ) S0016 ( Other Identifier: SWOG ) CALGB-50102 ( Other Identifier: CALGB ) S0016 ( Other Identifier: ECOG )
First Submitted:	December 6, 2000
First Posted:	January 27, 2003
Results First Submitted:	November 2, 2012
Results First Posted:	February 26, 2013
Last Update Posted:	September 26, 2023

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