S0433 Iodine I 131 Tositumomab, Rituximab, and Combination Chemotherapy in Treating Older Patients With Stage II, Stage III, or Stage IV Non-Hodgkin's Lymphoma

• Sponsor: Southwest Oncology Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00107380
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 86
• Locations: 78
• Arm: 1
• Duration (Months): 121
• Patients Per Site: 1.1
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Radiolabeled monoclonal antibodies, such as iodine I 131 tositumomab, can find cancer cells and carry cancer-killing substances to them without harming normal cells. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin, vincristine, and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving a radiolabeled monoclonal antibody together with rituximab and combination chemotherapy may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving iodine I 131 tositumomab together with rituximab and combination chemotherapy works in treating older patients with stage II, stage III, or stage IV B-cell non-Hodgkin's lymphoma.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Biological: rituximab; Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: prednisone; Drug: vincristine sulfate; Radiation: tositumomab and iodine I 131 tositumomab	Phase 2

Detailed Description

OBJECTIVES:

• Determine the 2-year progression-free survival of older patients with previously untreated bulky stage II or stage III or IV diffuse large B-cell non-Hodgkin's lymphoma treated with iodine I 131 tositumomab in combination with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone.

• Determine the response rate (partial response, complete unconfirmed response, and complete response) in patients treated with this regimen.

• Determine the 2-year progression-free survival and response rate (partial response, complete unconfirmed response, and complete response) in B-cell lymphoma 2 (BCL-2) positive patients treated with this regimen.

OUTLINE: This is a multicenter study.

• Rituximab and chemotherapy: Patients receive R-CHOP comprising rituximab IV over 6 hours; cyclophosphamide IV over 15-45 minutes; doxorubicin IV over 5-20 minutes; and vincristine IV over 5-15 minutes on day 1 and oral prednisone on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients then undergo a restaging evaluation. Patients without progressive disease receive CHOP chemotherapy comprising cyclophosphamide, doxorubicin, vincristine, and prednisone as outlined above. Treatment with CHOP chemotherapy repeats every 21 days for 2 courses.

• Radiolabeled monoclonal antibody therapy: Approximately 4-8 weeks after completion of chemotherapy, patients receive tositumomab IV over 1 hour followed by a dosimetric dose of iodine I 131 tositumomab IV over 20 minutes. Patients then undergo gamma scans over a 1-week period in order to determine the correct treatment dose of iodine I 131 tositumomab. No more than 2 weeks after administration of the dosimetric dose, patients receive tositumomab IV over 1 hour followed by a treatment dose of iodine I 131 tositumomab IV over 20 minutes.

After completion of study treatment, patients are followed periodically for up to 5 years.

PROJECTED ACCRUAL: A total of 80 patients will be accrued for this study within 15 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 86 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Iodine-131-Labeled Monoclonal Anti-B1 Antibody (I-131 Tositumomab) in Combination With Cyclophosphamide, Doxorubicin, Vincristine, Prednisone and Rituximab Therapy for Patients ≥ Age 60 With Advanced Stage Diffuse Large B-Cell NHL: A Phase II Study
• Study Start Date: Nov 1, 2005
• Actual Primary Completion Date: Nov 1, 2013
• Actual Study Completion Date: Dec 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: R-CHOP x 8 with I-131 Tositumomab Cyclophosphamide 750 mg/m2 IV Day 1 Doxorubicin 50 mg/m2 IV Day 1 Vincristine 1.4 mg/m2 IV Day 1 Prednisone 100 mg PO Days 1-5 Rituximab 375 mg/m2 IV Day 1 Q 21 Days x 6 cycles Unlabeled Anti-B1 Antibody 450 mg IV Day 170 Dosimetric dose 35 mg IV Day 170 Unlabeled Anti-B1 Antibody 450 mg IV Day 177 Therapeutic dose 35 mg IV Day 177	Biological: rituximab; Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: prednisone; Drug: vincristine sulfate; Radiation: tositumomab and iodine I 131 tositumomab

Outcome Measures

Primary Outcome Measures

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

   Clinical responses were evaluated according to International Workshop NHL criteria (Cheson et al, 1999). Progression disease was defined as if a (CR, CRU) was not achieved at a previous assessment, a 50% increase in the SPD of target measurable lesions over the smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline. Appearance of a new lesion/site. Unequivocal progression of non-measurable disease in the opinion of the treating physician (an explanation must be provided). Death due to disease without prior documentation of progression. PFS is measured from date of registration to date of first observation of progressive disease, or death due to any cause. Patients last known to be alive and progression-free are censored at date of last contact.

2. Response Rate (Complete, Complete Unconfirmed, and Partial) [6 months]

   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.

Secondary Outcome Measures

1. Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug [6 months (assessed at the end of each cycle of chemotherapy for 8 cycles (1 cycle= 21 days), at restaging, and at the end of each radiolabeled antibody treatment)]

   Adverse Events (AEs) are reported by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. 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 to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Diagnosis of diffuse large B-cell non-Hodgkin's lymphoma, meeting 1 of the following stage criteria:

• Bulky stage II disease

• Stage III disease

• Stage IV disease

• Confirmed cluster of differentiation antigen 20 (CD20) antigen-positive disease

• Bidimensionally measurable disease

• Less than 20,000/mcL circulating lymphoid cells on white blood cell (WBC) differential count

• Adequate sections AND a paraffin block OR ≥ 10 unstained sections from the original diagnostic specimen available

• Needle aspiration or cytology are not considered adequate

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

• No prior diagnosis of indolent lymphoma

• No histologic transformation

PATIENT CHARACTERISTICS:

Performance status

• Zubrod 0-2

Life expectancy

• Not specified

Hematopoietic

• See Disease Characteristics

Hepatic

• Not specified

Renal

• Not specified

Cardiovascular

• Ejection fraction ≥ 45% by multiple gated acquisition scan (MUGA) OR

• No significant abnormalities by echocardiogram

Pulmonary

• No requirement for continuous supplemental oxygen

Other

• Fertile patients must use effective contraception during and for 6 months after completion of study treatment

• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, stage I or II cancer in complete remission, or carcinoma in situ of the cervix

• No known HIV positivity

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior antibody therapy for lymphoma

Chemotherapy

• No prior chemotherapy for lymphoma

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy for lymphoma

Surgery

• No prior solid organ transplantation

Other

• Concurrent enrollment on protocol SWOG-8947 (lymphoma serum repository) or protocol SWOG-8819 (lymphoma tissue repository) is encouraged

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alaska Regional Hospital Cancer Center	Anchorage	Alaska	United States	99508
2	Arizona Cancer Center at University of Arizona Health Sciences Center	Tucson	Arizona	United States	85724-5024
3	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010-3000
4	Piedmont Hospital	Atlanta	Georgia	United States	30309
5	Northside Hospital Cancer Center	Atlanta	Georgia	United States	30342-1611
6	Saint Joseph's Hospital of Atlanta	Atlanta	Georgia	United States	30342-1701
7	CCOP - Atlanta Regional	Atlanta	Georgia	United States	30342
8	WellStar Cobb Hospital	Austell	Georgia	United States	30106
9	Charles B. Eberhart Cancer Center at DeKalb Medical Center	Decatur	Georgia	United States	30033
10	Gwinnett Medical Center	Lawrenceville	Georgia	United States	30045
11	Kennestone Cancer Center at Wellstar Kennestone Hospital	Marietta	Georgia	United States	30060
12	Southern Regional Medical Center	Riverdale	Georgia	United States	30274-2600
13	Harbin Clinic Cancer Center - Medical Oncology	Rome	Georgia	United States	30165
14	Saint Anthony's Hospital at Saint Anthony's Health Center	Alton	Illinois	United States	62002
15	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois	United States	60153
16	Good Samaritan Regional Health Center	Mt. Vernon	Illinois	United States	62864
17	St. Francis Hospital and Health Centers - Beech Grove Campus	Beech Grove	Indiana	United States	46107
18	Reid Hospital & Health Care Services	Richmond	Indiana	United States	47374
19	Cotton-O'Neil Cancer Center	Topeka	Kansas	United States	66606
20	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109-0942
21	Saint Francis Medical Center	Cape Girardeau	Missouri	United States	63703
22	Midwest Hematology Oncology Group, Incorporated	Saint Louis	Missouri	United States	63109
23	CCOP - St. Louis-Cape Girardeau	Saint Louis	Missouri	United States	63141
24	David C. Pratt Cancer Center at St. John's Mercy	Saint Louis	Missouri	United States	63141
25	CCOP - Montana Cancer Consortium	Billings	Montana	United States	59101
26	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana	United States	59101
27	Northern Rockies Radiation Oncology Center	Billings	Montana	United States	59101
28	St. Vincent Healthcare Cancer Care Services	Billings	Montana	United States	59101
29	Billings Clinic - Downtown	Billings	Montana	United States	59107-7000
30	Bozeman Deaconess Cancer Center	Bozeman	Montana	United States	59715
31	St. James Healthcare Cancer Care	Butte	Montana	United States	59701
32	Big Sky Oncology	Great Falls	Montana	United States	59405-5309
33	Great Falls Clinic - Main Facility	Great Falls	Montana	United States	59405
34	Sletten Cancer Institute at Benefis Healthcare	Great Falls	Montana	United States	59405
35		Great Falls	Montana	United States	59405
36	Northern Montana Hospital	Havre	Montana	United States	59501
37	St. Peter's Hospital	Helena	Montana	United States	59601
38	Glacier Oncology, PLLC	Kalispell	Montana	United States	59901
39	Kalispell Medical Oncology at KRMC	Kalispell	Montana	United States	59901
40	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
41	Community Medical Center	Missoula	Montana	United States	59801
42	Guardian Oncology and Center for Wellness	Missoula	Montana	United States	59804
43	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana	United States	59807-7877
44	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana	United States	59807
45	Falck Cancer Center at Arnot Ogden Medical Center	Elmira	New York	United States	14905
46	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York	United States	14642
47	Rutherford Hospital	Rutherfordton	North Carolina	United States	28139
48	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio	United States	44195
49	Grandview Hospital	Dayton	Ohio	United States	45405
50	Good Samaritan Hospital	Dayton	Ohio	United States	45406
51	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio	United States	45409
52	Samaritan North Cancer Care Center	Dayton	Ohio	United States	45415
53	CCOP - Dayton	Dayton	Ohio	United States	45420
54	Blanchard Valley Medical Associates	Findlay	Ohio	United States	45840
55	Middletown Regional Hospital	Franklin	Ohio	United States	45005-1066
56	Wayne Hospital	Greenville	Ohio	United States	45331
57	Cleveland Clinic Cancer Center	Independence	Ohio	United States	44131
58	Charles F. Kettering Memorial Hospital	Kettering	Ohio	United States	45429
59	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio	United States	45373-1300
60	Clinton Memorial Hospital	Wilmington	Ohio	United States	45177
61	Cleveland Clinic - Wooster	Wooster	Ohio	United States	44691
62	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio	United States	45385
63	AnMed Cancer Center	Anderson	South Carolina	United States	29621
64	CCOP - Upstate Carolina	Spartanburg	South Carolina	United States	29303
65	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina	United States	29303
66	St. Joseph Cancer Center	Bellingham	Washington	United States	98225
67	Olympic Hematology and Oncology	Bremerton	Washington	United States	98310
68	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98104
69	Harborview Medical Center	Seattle	Washington	United States	98104
70	Minor and James Medical, PLLC	Seattle	Washington	United States	98104
71	Group Health Central Hospital	Seattle	Washington	United States	98112
72	Swedish Cancer Institute at Swedish Medical Center - First Hill Campus	Seattle	Washington	United States	98122-4307
73	Polyclinic First Hill	Seattle	Washington	United States	98122
74	University Cancer Center at University of Washington Medical Center	Seattle	Washington	United States	98195-6043
75	Cancer Care Northwest - Spokane South	Spokane	Washington	United States	99202
76	Evergreen Hematology and Oncology, PS	Spokane	Washington	United States	99218
77	Rocky Mountain Oncology	Casper	Wyoming	United States	82609
78	Welch Cancer Center at Sheridan Memorial Hospital	Sheridan	Wyoming	United States	82801

Sponsors and Collaborators

• Southwest Oncology Group
• National Cancer Institute (NCI)

Investigators

• Study Chair: Jonathan W. Friedberg, MD, James P. Wilmot Cancer Center
• Study Director: Richard I. Fisher, MD, James P. Wilmot Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Southwest Oncology Group
• ClinicalTrials.gov Identifier: NCT00107380
• Other Study ID Numbers: CDR0000415955; S0433; U10CA032102
• First Posted: Apr 6, 2005
• Last Update Posted: Mar 7, 2016
• Last Verified: Feb 1, 2016

• Keywords provided by Southwest Oncology Group: contiguous stage II adult diffuse large cell lymphoma; noncontiguous stage II adult diffuse large cell lymphoma; stage III adult diffuse large cell lymphoma; stage IV adult diffuse large cell lymphoma
• Additional relevant MeSH terms: Lymphoma; Prednisone; Cyclophosphamide; Rituximab; Doxorubicin; Liposomal doxorubicin; Vincristine; Tositumomab I-131

Study Results

Participant Flow

Arm/Group Title	R-CHOP + I-131-tositumomab
Arm/Group Description	Patients receive cyclophosphamide 750 mg/m^2 IV over 15 minutes, doxorubicin 50 mg/m^2 IV, and vincristine IV on days 1, 22, 43, 64, 85, 106, 127, and 148. Patients also receive oral prednisone 100 mg daily on days 1-5, 22-26, 43-47, 64-68, 85-89, 106-110, 127-131, and 148-152; rituximab 375 mg/m^2 IV on days 1, 22, 43, 64, 85, and 106; unlabeled anti-B1 antibody 450 mg/m^2 IV and dosimetric dose 35 mg IV over 20 minutes on day 170, and unlabeled anti-B1 antibody 450 mg IV and therapeutic dose 35mg IV over 20 minutes on day 177.
Period Title: Overall Study
STARTED	86
Eligible	84
COMPLETED	56
NOT COMPLETED	30

Baseline Characteristics

Arm/Group Title	R-CHOP + I-131-tositumomab
Arm/Group Description	Patients receive cyclophosphamide 750 mg/m^2 IV over 15 minutes, doxorubicin 50 mg/m^2 IV, and vincristine IV on days 1, 22, 43, 64, 85, 106, 127, and 148. Patients also receive oral prednisone 100 mg daily on days 1-5, 22-26, 43-47, 64-68, 85-89, 106-110, 127-131, and 148-152; rituximab 375 mg/m^2 IV on days 1, 22, 43, 64, 85, and 106; unlabeled anti-B1 antibody 450 mg/m^2 IV and dosimetric dose 35 mg IV over 20 minutes on day 170, and unlabeled anti-B1 antibody 450 mg IV and therapeutic dose 35mg IV over 20 minutes on day 177
Overall Participants	84
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	63.8
Sex: Female, Male (Count of Participants)
Female	45 53.6%
Male	39 46.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 3.6%
Not Hispanic or Latino	65 77.4%
Unknown or Not Reported	16 19%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	3 3.6%
Native Hawaiian or Other Pacific Islander	1 1.2%
Black or African American	1 1.2%
White	78 92.9%
More than one race	0 0%
Unknown or Not Reported	1 1.2%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival (PFS) at 2 Years
Description	Clinical responses were evaluated according to International Workshop NHL criteria (Cheson et al, 1999). Progression disease was defined as if a (CR, CRU) was not achieved at a previous assessment, a 50% increase in the SPD of target measurable lesions over the smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline. Appearance of a new lesion/site. Unequivocal progression of non-measurable disease in the opinion of the treating physician (an explanation must be provided). Death due to disease without prior documentation of progression. PFS is measured from date of registration to date of first observation of progressive disease, or death due to any cause. Patients last known to be alive and progression-free are censored at date of last contact.
Time Frame	0-2 years

Outcome Measure Data

Analysis Population Description

All eligible patients who started treatment were included in the analysis

Arm/Group Title	R-CHOP + I-131-tositumomab
Arm/Group Description	Patients receive cyclophosphamide 750 mg/m^2 IV over 15 minutes, doxorubicin 50 mg/m^2 IV, and vincristine IV on days 1, 22, 43, 64, 85, 106, 127, and 148. Patients also receive oral prednisone 100 mg daily on days 1-5, 22-26, 43-47, 64-68, 85-89, 106-110, 127-131, and 148-152; rituximab 375 mg/m^2 IV on days 1, 22, 43, 64, 85, and 106; unlabeled anti-B1 antibody 450 mg/m^2 IV and dosimetric dose 35 mg IV over 20 minutes on day 170, and unlabeled anti-B1 antibody 450 mg IV and therapeutic dose 35mg IV over 20 minutes on day 177
Measure Participants	84
Number (95% Confidence Interval) [percentage of participants]	69 82.1%

2. Primary Outcome

Title	Response Rate (Complete, Complete Unconfirmed, and Partial)
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	6 months

Outcome Measure Data

Analysis Population Description

All eligible patients who started treatment were included in the analysis

Arm/Group Title	R-CHOP + I-131-tositumomab
Arm/Group Description	Patients receive cyclophosphamide 750 mg/m^2 IV over 15 minutes, doxorubicin 50 mg/m^2 IV, and vincristine IV on days 1, 22, 43, 64, 85, 106, 127, and 148. Patients also receive oral prednisone 100 mg daily on days 1-5, 22-26, 43-47, 64-68, 85-89, 106-110, 127-131, and 148-152; rituximab 375 mg/m^2 IV on days 1, 22, 43, 64, 85, and 106; unlabeled anti-B1 antibody 450 mg/m^2 IV and dosimetric dose 35 mg IV over 20 minutes on day 170, and unlabeled anti-B1 antibody 450 mg IV and therapeutic dose 35mg IV over 20 minutes on day 177.
Measure Participants	84
Partial Response	21 25%
Confirmed Response	41 48.8%
Unconfirmed Response	10 11.9%
No Response	12 14.3%

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 3.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal.
Time Frame	6 months (assessed at the end of each cycle of chemotherapy for 8 cycles (1 cycle= 21 days), at restaging, and at the end of each radiolabeled antibody treatment)

Outcome Measure Data

Analysis Population Description

Eligible patients who had received any treatment were included in the adverse event summaries. Any CTCAE 3.0 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	R-CHOP + I-131-tositumomab
Arm/Group Description	Patients receive cyclophosphamide 750 mg/m^2 IV over 15 minutes, doxorubicin 50 mg/m^2 IV, and vincristine IV on days 1, 22, 43, 64, 85, 106, 127, and 148. Patients also receive oral prednisone 100 mg daily on days 1-5, 22-26, 43-47, 64-68, 85-89, 106-110, 127-131, and 148-152; rituximab 375 mg/m^2 IV on days 1, 22, 43, 64, 85, and 106; unlabeled anti-B1 antibody 450 mg/m^2 IV and dosimetric dose 35 mg IV over 20 minutes on day 170, and unlabeled anti-B1 antibody 450 mg IV and therapeutic dose 35mg IV over 20 minutes on day 177
Measure Participants	84
Anorexia	2 2.4%
Calcium, serum-low (hypocalcemia)	1 1.2%
Cardiac troponin I (cTnI)	1 1.2%
Cardiac-ischemia/infarction	3 3.6%
Constipation	1 1.2%
Cough	1 1.2%
Dehydration	1 1.2%
Dizziness	1 1.2%
Dyspnea (shortness of breath)	2 2.4%
Fatigue (asthenia, lethargy, malaise)	12 14.3%
Febrile neutropenia	14 16.7%
Gastrointestinal-Other (Specify: GI bleed)	1 1.2%
Glucose, serum-high (hyperglycemia)	5 6%
Hearing: pts w/o audiogram not enroll monitor prgm	1 1.2%
Hemoglobin	12 14.3%
Hemorrhage, GI - Rectum	1 1.2%
Hemorrhage, GU - Urinary NOS	1 1.2%
Hypotension	1 1.2%
Inf (clin/microbio) w/Gr 3-4 neuts - Blood	2 2.4%
Inf (clin/microbio) w/Gr 3-4 neuts - Skin	1 1.2%
Inf (clin/microbio) w/Gr 3-4 neuts - UTI	2 2.4%
Inf (clin/microbio) w/Gr 3-4 neuts - Upper airway	1 1.2%
Inf w/normal ANC or Gr 1-2 neutrophils - Blood	2 2.4%
Inf w/normal ANC or Gr 1-2 neutrophils - Dental	1 1.2%
Inf w/normal ANC or Gr 1-2 neutrophils - Lung	2 2.4%
Inf w/normal ANC or Gr 1-2 neutrophils - UTI	1 1.2%
Left ventricular systolic dysfunction	1 1.2%
Leukocytes (total WBC)	47 56%
Lymphopenia	39 46.4%
Mood alteration - anxiety	1 1.2%
Muscle weakness, not d/t neuropathy - body/general	1 1.2%
Nausea	1 1.2%
Neurology-Other (Specify: restless leg syndrom)	1 1.2%
Neuropathy: motor	1 1.2%
Neuropathy: sensory	8 9.5%
Neutrophils/granulocytes (ANC/AGC)	55 65.5%
Opportunistic inf associated w/gt=Gr 2 lymphopenia	2 2.4%
Pain - Abdomen NOS	2 2.4%
Pain - Back	1 1.2%
Pain - Esophagus	1 1.2%
Pain - Head/headache	1 1.2%
Phosphate, serum-low (hypophosphatemia)	1 1.2%
Platelets	29 34.5%
Pneumonitis/pulmonary infiltrates	1 1.2%
Potassium, serum-low (hypokalemia)	2 2.4%
Renal failure	1 1.2%
Restrictive cardiomyopathy	1 1.2%
SVT and nodal arrhythmia - Atrial fibrillation	1 1.2%
SVT and nodal arrhythmia - SVT tachycardia	1 1.2%
Secondary Malignancy-poss rel to cancer Tx	2 2.4%
Sodium, serum-low (hyponatremia)	1 1.2%
Thrombosis/thrombus/embolism	2 2.4%
Uric acid, serum-high (hyperuricemia)	1 1.2%
Vision-blurred vision	1 1.2%

Adverse Events

Time Frame	6 months (assessed at the end of each cycle of chemotherapy for 8 cycles (1 cycle= 21 days), at restaging, and at the end of each radiolabeled antibody treatment)
Arm/Group Title	R-CHOP + I-131-tositumomab
Arm/Group Description	Patients receive cyclophosphamide 750 mg/m^2 IV over 15 minutes, doxorubicin 50 mg/m^2 IV, and vincristine IV on days 1, 22, 43, 64, 85, 106, 127, and 148. Patients also receive oral prednisone 100 mg daily on days 1-5, 22-26, 43-47, 64-68, 85-89, 106-110, 127-131, and 148-152; rituximab 375 mg/m^2 IV on days 1, 22, 43, 64, 85, and 106; unlabeled anti-B1 antibody 450 mg/m^2 IV and dosimetric dose 35 mg IV over 20 minutes on day 170, and unlabeled anti-B1 antibody 450 mg IV and therapeutic dose 35mg IV over 20 minutes on day 177
All Cause Mortality
	R-CHOP + I-131-tositumomab
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	R-CHOP + I-131-tositumomab
	Affected / at Risk (%)	# Events
Total	8/84 (9.5%)
Blood and lymphatic system disorders
Febrile neutropenia	1/84 (1.2%)
Cardiac disorders
Cardiac-ischemia/infarction	2/84 (2.4%)
Gastrointestinal disorders
Hemorrhage, GI - Rectum	1/84 (1.2%)
Hemorrhage, GI - Upper GI NOS	1/84 (1.2%)
Infections and infestations
Inf w/normal ANC or Gr 1-2 neutrophils - Lung	1/84 (1.2%)
Investigations
Platelets	1/84 (1.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Secondary Malignancy-poss rel to cancer Tx	2/84 (2.4%)
Renal and urinary disorders
Renal failure	1/84 (1.2%)
Other (Not Including Serious) Adverse Events
	R-CHOP + I-131-tositumomab
	Affected / at Risk (%)	# Events
Total	84/84 (100%)
Blood and lymphatic system disorders
Febrile neutropenia	13/84 (15.5%)
Hemoglobin	70/84 (83.3%)
Eye disorders
Vision-blurred vision	5/84 (6%)
Gastrointestinal disorders
Constipation	40/84 (47.6%)
Diarrhea	22/84 (26.2%)
Gastrointestinal-Other (Specify)	7/84 (8.3%)
Mucositis/stomatitis (clinical exam) - Oral cavity	15/84 (17.9%)
Mucositis/stomatitis (functional/symp) - Oral cav	12/84 (14.3%)
Nausea	45/84 (53.6%)
Pain - Abdomen NOS	20/84 (23.8%)
Pain - Oral cavity	5/84 (6%)
Vomiting	12/84 (14.3%)
General disorders
Constitutional Symptoms-Other (Specify)	6/84 (7.1%)
Edema: head and neck	5/84 (6%)
Edema: limb	20/84 (23.8%)
Fatigue (asthenia, lethargy, malaise)	72/84 (85.7%)
Fever in absence of neutropenia, ANC lt1.0x10e9/L	18/84 (21.4%)
Pain-Other (Specify)	11/84 (13.1%)
Rigors/chills	11/84 (13.1%)
Immune system disorders
Allergic reaction/hypersensitivity	9/84 (10.7%)
Infections and infestations
Inf w/normal ANC or Gr 1-2 neutrophils - Sinus	5/84 (6%)
Investigations
ALT, SGPT (serum glutamic pyruvic transaminase)	20/84 (23.8%)
AST, SGOT	27/84 (32.1%)
Alkaline phosphatase	13/84 (15.5%)
Creatinine	18/84 (21.4%)
Leukocytes (total WBC)	70/84 (83.3%)
Lymphopenia	54/84 (64.3%)
Metabolic/Laboratory-Other (Specify)	8/84 (9.5%)
Neutrophils/granulocytes (ANC/AGC)	68/84 (81%)
Platelets	62/84 (73.8%)
Weight gain	6/84 (7.1%)
Weight loss	19/84 (22.6%)
Metabolism and nutrition disorders
Albumin, serum-low (hypoalbuminemia)	18/84 (21.4%)
Anorexia	23/84 (27.4%)
Calcium, serum-low (hypocalcemia)	11/84 (13.1%)
Dehydration	6/84 (7.1%)
Glucose, serum-high (hyperglycemia)	47/84 (56%)
Glucose, serum-low (hypoglycemia)	8/84 (9.5%)
Potassium, serum-low (hypokalemia)	10/84 (11.9%)
Sodium, serum-low (hyponatremia)	9/84 (10.7%)
Musculoskeletal and connective tissue disorders
Muscle weakness, not d/t neuropathy - body/general	15/84 (17.9%)
Pain - Back	15/84 (17.9%)
Pain - Bone	18/84 (21.4%)
Pain - Chest wall	5/84 (6%)
Pain - Extremity-limb	13/84 (15.5%)
Pain - Joint	14/84 (16.7%)
Pain - Muscle	12/84 (14.3%)
Nervous system disorders
Dizziness	18/84 (21.4%)
Neuropathy: motor	5/84 (6%)
Neuropathy: sensory	48/84 (57.1%)
Pain - Head/headache	22/84 (26.2%)
Taste alteration (dysgeusia)	17/84 (20.2%)
Psychiatric disorders
Insomnia	23/84 (27.4%)
Mood alteration - agitation	5/84 (6%)
Mood alteration - anxiety	18/84 (21.4%)
Mood alteration - depression	13/84 (15.5%)
Renal and urinary disorders
Urinary frequency/urgency	8/84 (9.5%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	13/84 (15.5%)
Cough	24/84 (28.6%)
Dyspnea (shortness of breath)	23/84 (27.4%)
Pain - Throat/pharynx/larynx	5/84 (6%)
Pulmonary/Upper Respiratory-Other (Specify)	7/84 (8.3%)
Skin and subcutaneous tissue disorders
Dermatology/Skin-Other (Specify)	8/84 (9.5%)
Dry skin	6/84 (7.1%)
Hair loss/Alopecia (scalp or body)	51/84 (60.7%)
Nail changes	6/84 (7.1%)
Pruritus/itching	5/84 (6%)
Rash/desquamation	13/84 (15.5%)
Rash: acne/acneiform	5/84 (6%)
Sweating (diaphoresis)	14/84 (16.7%)
Vascular disorders
Hypotension	14/84 (16.7%)

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.