A Phase 3 interventional study of rituximab and cyclophosphamide in Lymphoma, sponsored by SWOG Cancer Research Network. Completed at 259 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-03-16.
Sponsored by SWOG Cancer Research Network · Phase 3, Interventional, and Treatment
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.
OBJECTIVES:
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)
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)
5,578 studies on the registry are indexed under Lymphoma; 825 are open to participants now.
This study's enrollment of 571 is above the median of 40 across 4,508 interventional studies indexed under Lymphoma.
Browse Lymphoma studies →SWOG Cancer Research Network is the lead sponsor of 328 studies on the registry; 37 are open to participants now.
Of its 17 completed or terminated interventional studies of FDA-regulated products, 17 (100%) have results posted.
Counted across the registry records on this site, refreshed daily.
DISEASE CHARACTERISTICS:
Histologically confirmed previously untreated bulky stage II or stage III or IV follicular non-Hodgkin's lymphoma
PATIENT CHARACTERISTICS:
Age:
Performance status:
Life expectancy:
Hematopoietic:
Hepatic:
Renal:
Cardiovascular:
No impaired cardiac status, including:
Other:
PRIOR CONCURRENT THERAPY:
Biologic therapy:
Chemotherapy:
No prior chemotherapy for lymphoma
Endocrine therapy:
Radiotherapy:
Surgery:
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 · Drug: doxorubicin · Drug: prednisone · Drug: vincristine
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 · Drug: cyclophosphamide · Drug: doxorubicin · Drug: prednisone · Drug: vincristine
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 · Drug: doxorubicin · Drug: prednisone · Drug: vincristine · Radiation: tositumomab
Given IV
Also known as: rituxan
Given IV
Also known as: cytoxan
Given IV
Also known as: adriamycin
Given orally
Also known as: steroid
Given IV
Also known as: oncovin
Given IV
Progression-free Survival at 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
Time frame: 0-2 years
Progression-free Survival at 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
Time frame: 0-5 years
Overall Survival at 2 Years
Measured from date of registration to date of death due to any cause
Time frame: 0-2 years
Overall Survival at 5 Years
Measured from date of registration to date of death due to any cause
Time frame: 0-5 years
Objective Response (Confirmed and Unconfirmed Complete and Partial Responses)
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
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug
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
| Milestone | CHOP Only | CHOP + Rituximab | CHOP + Tositumomab |
|---|---|---|---|
| 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 |
| Withdrew: Adverse event | 0 | 4 | 4 |
| Withdrew: Refusal unrelated to adverse event | 1 | 0 | 8 |
| Withdrew: Progression/relapse | 0 | 1 | 2 |
| Withdrew: Death | 0 | 1 | 2 |
| Withdrew: Other - not protocol specified | 0 | 7 | 7 |
| Withdrew: Ineligible | 2 | 12 | 10 |
| Withdrew: Eligible but no treatment received | 1 | 0 | 0 |
Measured from time of registration to date of of first observation of progression/relapse, or death due to any cause, or last contact date
| percentage of participants | CHOP + Rituximab | CHOP + Tositumomab |
|---|---|---|
| Progression-free Survival at 2 Years | 76 | 80 |
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.
| participants | CHOP + Rituximab | CHOP + Tositumomab |
|---|---|---|
| Objective Response (Confirmed and Unconfirmed Complete and Partial Responses) | 224 | 223 |
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
| Participants | CHOP Only | CHOP + Rituximab | CHOP + Tositumomab |
|---|---|---|---|
| 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 |
Measured from time of registration to date of of first observation of progression/relapse, or death due to any cause, or last contact date
| percentage of participants | CHOP + Rituximab | CHOP + Tositumomab |
|---|---|---|
| Progression-free Survival at 5 Years | 60 | 66 |
Measured from date of registration to date of death due to any cause
| percentage of participants | CHOP + Rituximab | CHOP + Tositumomab |
|---|---|---|
| Overall Survival at 2 Years | 97 | 93 |
Measured from date of registration to date of death due to any cause
| percentage of participants | CHOP + Rituximab | CHOP + Tositumomab |
|---|---|---|
| Overall Survival at 5 Years | 92 | 86 |
Collected over 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. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| CHOP Only | — | 0/13 (0%) | 13/13 (100%) |
| CHOP + Rituximab | — | 3/263 (1.1%) | 262/263 (99.6%) |
| CHOP + Tositumomab | — | 16/263 (6.1%) | 261/263 (99.2%) |
| Event | CHOP Only | CHOP + Rituximab | CHOP + Tositumomab |
|---|---|---|---|
| Second primaryNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 0/13 | 0/263 | 6/263 |
| Hematologic-otherBlood and lymphatic system disorders | 0/13 | 0/263 | 3/263 |
| Febrile neutropeniaBlood and lymphatic system disorders | 0/13 | 0/263 | 2/263 |
| Infection w/o 3-4 neutropeniaInfections and infestations | 0/13 | 0/263 | 2/263 |
| Platelet transfusionBlood and lymphatic system disorders | 0/13 | 0/263 | 1/263 |
| LVEF decrease/CHFCardiac disorders | 0/13 | 0/263 | 1/263 |
| PancreatitisGastrointestinal disorders | 0/13 | 1/263 | 0/263 |
| Respiratory infect w/ neutropInfections and infestations | 0/13 | 0/263 | 1/263 |
| Neutropenia/granulocytopeniaInvestigations | 0/13 | 0/263 | 1/263 |
| Cerebrovascular ischemiaNervous system disorders | 0/13 | 1/263 | 0/263 |
| Event | CHOP Only | CHOP + Rituximab | CHOP + Tositumomab |
|---|---|---|---|
| LeukopeniaInvestigations | 11/13 | 187/263 | 205/263 |
| AlopeciaSkin and subcutaneous tissue disorders | 11/13 | 176/263 | 151/263 |
| Fatigue/malaise/lethargyGeneral disorders | 7/13 | 207/263 | 198/263 |
| Neutropenia/granulocytopeniaInvestigations | 10/13 | 174/263 | 187/263 |
| AnemiaBlood and lymphatic system disorders | 5/13 | 177/263 | 192/263 |
| NauseaGastrointestinal disorders | 6/13 | 149/263 | 173/263 |
| LymphopeniaInvestigations | 7/13 | 145/263 | 155/263 |
| Sensory neuropathyNervous system disorders | 7/13 | 120/263 | 119/263 |
| ThrombocytopeniaInvestigations | 3/13 | 77/263 | 140/263 |
| Constipation/bowel obstructionGastrointestinal disorders | 4/13 | 106/263 | 99/263 |
| Age, Continuous(years) | CHOP + Rituximab | CHOP + Tositumomab | CHOP Only | Total |
|---|---|---|---|---|
| Median | 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(Participants) | CHOP + Rituximab | CHOP + Tositumomab | CHOP Only | Total |
|---|---|---|---|---|
| Female | 125 | 118 | 4 | 247 |
| Male | 142 | 147 | 10 | 299 |
| Ethnicity (NIH/OMB)(Participants) | CHOP + Rituximab | CHOP + Tositumomab | CHOP Only | Total |
|---|---|---|---|---|
| Hispanic or Latino | 6 | 10 | 0 | 16 |
| Not Hispanic or Latino | 232 | 220 | 14 | 466 |
| Unknown or Not Reported | 29 | 35 | 0 | 64 |
| Race (NIH/OMB)(Participants) | CHOP + Rituximab | CHOP + Tositumomab | CHOP Only | Total |
|---|---|---|---|---|
| American Indian or Alaska Native | 1 | 2 | 0 | 3 |
| Asian | 5 | 3 | 1 | 9 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 |
| Black or African American | 11 | 10 | 0 | 21 |
| White | 241 | 238 | 13 | 492 |
| More than one race | 1 | 0 | 0 | 1 |
| Unknown or Not Reported | 8 | 12 | 0 | 20 |
Showing the first 100 of 259 sites.
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