S0801 Iodine I 131 Tositumomab, Rituximab, and Combination Chemotherapy in Previously Untreated Stage II, Stage III, or Stage IV Follicular Non-Hodgkin Lymphoma
- Conditions
- Lymphoma
- Interventions
- Biological: rituximabRadiation: tositumomab
- Registration Number
- NCT00770224
- Lead Sponsor
- SWOG Cancer Research Network
- 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 the side effects of giving iodine I 131 tositumomab together with rituximab and combination chemotherapy and to see how well it works in treating patients with previously untreated stage II, stage III, or stage IV follicular non-Hodgkin lymphoma.
- Detailed Description
OBJECTIVES:
* To evaluate the response rate in patients with previously untreated stage II-IV follicular non-Hodgkin lymphoma treated with rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone (R-CHOP) in combination with iodine I 131 tositumomab.
* To evaluate the toxicity of this regimen in these patients.
* To estimate the 3-year progression-free survival rate in patients treated with this regimen.
* To estimate the 5-year progression-free and overall survival rate in patients treated with this regimen.
* To assess the safety profile of this regimen in these patients.
OUTLINE: This is a multicenter study.
* Induction therapy: Patients receive R-CHOP\* comprising rituximab IV, cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 1 and oral prednisone once daily on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with at least stable disease then proceed to consolidation therapy.
NOTE: \*Patients receive R-CHOP in courses 1-4 and CHOP alone in courses 5 and 6.
* Consolidation therapy: Within 12 weeks after completion of induction therapy, patients receive tositumomab IV over 1 hour followed by a dosimetric dose of iodine I 131 tositumomab IV over 20 minutes. Patients then undergo whole body gamma camera scans over a 1-week period to determine the rate of total body clearance of radioactivity and the therapeutic dose of iodine I 131 tositumomab. Within 7-14 days after the dosimetric dose, patients receive tositumomab IV over 1 hour followed by a therapeutic dose of iodine I 131 tositumomab IV over 20 minutes. Patients with at least stable disease then proceed to maintenance therapy.
* Maintenance therapy: Beginning approximately 1 year after study entry and no more than 28 days after restaging, patients receive rituximab IV every 3 months for up to 4 years (16 courses) in the absence of disease progression or unacceptable toxicity.
After completion of maintenance therapy, patients are followed annually for up to 7 years. Patients who do not complete maintenance therapy are followed every 6 months for 2 years and then annually for up to 7 years.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 87
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description R-CHOP, tositumomab and rituximab rituximab 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 Patients are restaged by CT scan. Unlabeled tositumomab antibody 450 mg IV within 12 after Cycle 6 of CHOP. Dosimetric dose 35 mg IV after infusion of unlabeled tositumomab antibody. Unlabeled tositumomab antibody 450 mg IV 7-14 days after dosimetric dose. Therapeutic dose 35 mg IV after infusion of unlabeled tositumomab antibody. Rituximab 375 mg/m2 IV q 3 months x 4 years beginning 1 year after registration. R-CHOP, tositumomab and rituximab 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 Patients are restaged by CT scan. Unlabeled tositumomab antibody 450 mg IV within 12 after Cycle 6 of CHOP. Dosimetric dose 35 mg IV after infusion of unlabeled tositumomab antibody. Unlabeled tositumomab antibody 450 mg IV 7-14 days after dosimetric dose. Therapeutic dose 35 mg IV after infusion of unlabeled tositumomab antibody. Rituximab 375 mg/m2 IV q 3 months x 4 years beginning 1 year after registration. R-CHOP, tositumomab and rituximab doxorubicin 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 Patients are restaged by CT scan. Unlabeled tositumomab antibody 450 mg IV within 12 after Cycle 6 of CHOP. Dosimetric dose 35 mg IV after infusion of unlabeled tositumomab antibody. Unlabeled tositumomab antibody 450 mg IV 7-14 days after dosimetric dose. Therapeutic dose 35 mg IV after infusion of unlabeled tositumomab antibody. Rituximab 375 mg/m2 IV q 3 months x 4 years beginning 1 year after registration. R-CHOP, tositumomab and rituximab cyclophosphamide 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 Patients are restaged by CT scan. Unlabeled tositumomab antibody 450 mg IV within 12 after Cycle 6 of CHOP. Dosimetric dose 35 mg IV after infusion of unlabeled tositumomab antibody. Unlabeled tositumomab antibody 450 mg IV 7-14 days after dosimetric dose. Therapeutic dose 35 mg IV after infusion of unlabeled tositumomab antibody. Rituximab 375 mg/m2 IV q 3 months x 4 years beginning 1 year after registration. R-CHOP, tositumomab and rituximab prednisone 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 Patients are restaged by CT scan. Unlabeled tositumomab antibody 450 mg IV within 12 after Cycle 6 of CHOP. Dosimetric dose 35 mg IV after infusion of unlabeled tositumomab antibody. Unlabeled tositumomab antibody 450 mg IV 7-14 days after dosimetric dose. Therapeutic dose 35 mg IV after infusion of unlabeled tositumomab antibody. Rituximab 375 mg/m2 IV q 3 months x 4 years beginning 1 year after registration. R-CHOP, tositumomab and rituximab vincristine 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 Patients are restaged by CT scan. Unlabeled tositumomab antibody 450 mg IV within 12 after Cycle 6 of CHOP. Dosimetric dose 35 mg IV after infusion of unlabeled tositumomab antibody. Unlabeled tositumomab antibody 450 mg IV 7-14 days after dosimetric dose. Therapeutic dose 35 mg IV after infusion of unlabeled tositumomab antibody. Rituximab 375 mg/m2 IV q 3 months x 4 years beginning 1 year after registration.
- Primary Outcome Measures
Name Time Method Percentage of Participants With 3-year Progression-free Survival (PFS) 0-3 years Measured from date of registration to date of first observation of progressive disease or death due to any cause. Progressive disease is ≥ 50% increase in the sum of products of greatest diameters (SPD) of target measurable nodal lesions over the smallest sum observed (over baseline if no decrease during therapy), or ≥ 50% increase in the greatest transverse diameter (GTD) of any node \> 1 cm in shortest axis, or ≥ 50% increase in the SPD of other target measurable lesions (e.g., splenic or hepatic nodules) over the smallest sum observed. Appearance of any new bone marrow involvement; appearance of a new lesion/site; lymph nodes with the long axis is \> 1.5 cm, or if the both the long and short axes are \> 1 cm; in patients with no pretreatment PET scan or when the PET scan was positive before therapy, lesions should be PET positive; or death due to disease without prior documentation of progression.
- Secondary Outcome Measures
Name Time Method Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug up to 5 years (1 year induction + 4 years maintenance therapy) or time of disease progression. Adverse Events (AEs) are reported by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal.
5-year Overall Survival 0-5 years Measured from date of registration to date of death due to any cause. Patients last known to be alive and are censored at date of last contact.
5-year Progression-free Survival 0-5 years Measured from date of registration to date of first observation of progressive disease or death due to any cause. Progressive disease is ≥ 50% increase in the sum of products of greatest diameters (SPD) of target measurable nodal lesions over the smallest sum observed (over baseline if no decrease during therapy), or ≥ 50% increase in the greatest transverse diameter (GTD) of any node \> 1 cm in shortest axis, or ≥ 50% increase in the SPD of other target measurable lesions (e.g., splenic or hepatic nodules) over the smallest sum observed. Appearance of any new bone marrow involvement; appearance of a new lesion/site; lymph nodes with the long axis is \> 1.5 cm, or if the both the long and short axes are \> 1 cm; in patients with no pretreatment PET scan or when the PET scan was positive before therapy, lesions should be PET positive; or death due to disease without prior documentation of progression.
Response Rate up to 5 years (1 year induction + 4 years maintenance therapy) or time of disease progression Complete (CR), complete unconfirmed (CRU) and partial responses (PR). CR is complete disappearance of all measurable and non-measurable disease with the exception of the following. Positron emission tomography (PET) must be negative if no pre-treatment PET scan or when the PET was positive before therapy. If the PET scan was negative before therapy, all nodal masses must have regressed. no new lesions; previously enlarged organs must have regressed in size; and if bone marrow positive at baseline, it must be negative. PR is ≥ 50% decrease in sum of products of greatest diameters (SPD) for up to six identified dominant lesions identified at baseline; no new lesions; no increase in the size of liver, spleen or other nodes; and splenic and hepatic nodules must have regressed in size by at least 50% in SPD. In patients with no pre-treatment PET scan or when the PET scan was positive before therapy, PET should be positive in at least one previously involved site.
Trial Locations
- Locations (114)
Doctors Hospital at Ohio Health
🇺🇸Columbus, Ohio, United States
CCOP - Columbus
🇺🇸Columbus, Ohio, United States
Cancer Center of Kansas, PA - Medical Arts Tower
🇺🇸Wichita, Kansas, United States
Cancer Center of Kansas, PA - Dodge City
🇺🇸Dodge City, Kansas, United States
Hematology-Oncology Centers of the Northern Rockies - Billings
🇺🇸Billings, Montana, United States
Alvin and Lois Lapidus Cancer Institute at Sinai Hospital
🇺🇸Baltimore, Maryland, United States
Munson Medical Center
🇺🇸Traverse City, Michigan, United States
Mount Carmel Health - West Hospital
🇺🇸Columbus, Ohio, United States
Billings Clinic - Downtown
🇺🇸Billings, Montana, United States
Saint Francis Medical Center
🇺🇸Cape Girardeau, Missouri, United States
Rutherford Hospital
🇺🇸Rutherfordton, North Carolina, United States
Butterworth Hospital at Spectrum Health
🇺🇸Grand Rapids, Michigan, United States
Lacks Cancer Center at Saint Mary's Health Care
🇺🇸Grand Rapids, Michigan, United States
St. Vincent Healthcare Cancer Care Services
🇺🇸Billings, Montana, United States
Adena Regional Medical Center
🇺🇸Chillicothe, Ohio, United States
Mecosta County Medical Center
🇺🇸Big Rapids, Michigan, United States
David C. Pratt Cancer Center at St. John's Mercy
🇺🇸Saint Louis, Missouri, United States
James P. Wilmot Cancer Center at University of Rochester Medical Center
🇺🇸Rochester, New York, United States
Battle Creek Health System Cancer Care Center
🇺🇸Battle Creek, Michigan, United States
Samaritan North Cancer Care Center
🇺🇸Dayton, Ohio, United States
CCOP - Dayton
🇺🇸Dayton, Ohio, United States
Grady Memorial Hospital
🇺🇸Delaware, Ohio, United States
Knox Community Hospital
🇺🇸Mount Vernon, Ohio, United States
UVMC Cancer Care Center at Upper Valley Medical Center
🇺🇸Troy, Ohio, United States
David L. Rike Cancer Center at Miami Valley Hospital
🇺🇸Dayton, Ohio, United States
Fairfield Medical Center
🇺🇸Lancaster, Ohio, United States
Charles F. Kettering Memorial Hospital
🇺🇸Kettering, Ohio, United States
Strecker Cancer Center at Marietta Memorial Hospital
🇺🇸Marietta, Ohio, United States
Clinton Memorial Hospital
🇺🇸Wilmington, Ohio, United States
Harborview Medical Center
🇺🇸Seattle, Washington, United States
Group Health Central Hospital
🇺🇸Seattle, Washington, United States
Minor and James Medical, PLLC
🇺🇸Seattle, Washington, United States
Fred Hutchinson Cancer Research Center
🇺🇸Seattle, Washington, United States
Cancer Center of Kansas, PA - Salina
🇺🇸Salina, Kansas, United States
Cancer Center of Kansas, PA - Wellington
🇺🇸Wellington, Kansas, United States
Cancer Center of Kansas, PA - Newton
🇺🇸Newton, Kansas, United States
Cancer Center of Kansas, PA - Winfield
🇺🇸Winfield, Kansas, United States
Wesley Medical Center
🇺🇸Wichita, Kansas, United States
Cancer Center of Kansas, PA - Pratt
🇺🇸Pratt, Kansas, United States
Tammy Walker Cancer Center at Salina Regional Health Center
🇺🇸Salina, Kansas, United States
Cotton-O'Neil Cancer Center
🇺🇸Topeka, Kansas, United States
Cancer Center of Kansas, PA - Wichita
🇺🇸Wichita, Kansas, United States
Cancer Center of Kansas, PA - Kingman
🇺🇸Kingman, Kansas, United States
Cancer Center of Kansas, PA - Parsons
🇺🇸Parsons, Kansas, United States
Cancer Center of Kansas-Independence
🇺🇸Independence, Kansas, United States
Associates in Womens Health, PA - North Review
🇺🇸Wichita, Kansas, United States
CCOP - Wichita
🇺🇸Wichita, Kansas, United States
Cancer Center of Kansas, PA - Chanute
🇺🇸Chanute, Kansas, United States
Lawrence Memorial Hospital
🇺🇸Lawrence, Kansas, United States
Cancer Center of Kansas - Fort Scott
🇺🇸Fort Scott, Kansas, United States
Providence Cancer Center at Providence Hospital
🇺🇸Mobile, Alabama, United States
Saint Anthony's Hospital at Saint Anthony's Health Center
🇺🇸Alton, Illinois, United States
Crossroads Cancer Center
🇺🇸Effingham, Illinois, United States
Decatur Memorial Hospital Cancer Care Institute
🇺🇸Decatur, Illinois, United States
Cancer Care Center of Decatur
🇺🇸Decatur, Illinois, United States
Good Samaritan Regional Health Center
🇺🇸Mount Vernon, Illinois, United States
Regional Cancer Center at Memorial Medical Center
🇺🇸Springfield, Illinois, United States
Cancer Center of Kansas, PA - El Dorado
🇺🇸El Dorado, Kansas, United States
Via Christi Cancer Center at Via Christi Regional Medical Center
🇺🇸Wichita, Kansas, United States
Midwest Hematology Oncology Group, Incorporated
🇺🇸Saint Louis, Missouri, United States
CCOP - St. Louis-Cape Girardeau
🇺🇸Saint Louis, Missouri, United States
Great Falls Clinic - Main Facility
🇺🇸Great Falls, Montana, United States
Riverside Methodist Hospital Cancer Care
🇺🇸Columbus, Ohio, United States
Blanchard Valley Medical Associates
🇺🇸Findlay, Ohio, United States
Licking Memorial Cancer Care Program at Licking Memorial Hospital
🇺🇸Newark, Ohio, United States
Ruth G. McMillan Cancer Center at Greene Memorial Hospital
🇺🇸Xenia, Ohio, United States
AnMed Cancer Center
🇺🇸Anderson, South Carolina, United States
St. Joseph Cancer Center
🇺🇸Bellingham, Washington, United States
Huntsman Cancer Institute at University of Utah
🇺🇸Salt Lake City, Utah, United States
Rocky Mountain Oncology
🇺🇸Casper, Wyoming, United States
Arizona Cancer Center at University of Arizona Health Sciences Center
🇺🇸Tucson, Arizona, United States
Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
🇺🇸Missoula, Montana, United States
CCOP - Montana Cancer Consortium
🇺🇸Billings, Montana, United States
Metro Health Hospital
🇺🇸Wyoming, Michigan, United States
Sletten Cancer Institute at Benefis Healthcare
🇺🇸Great Falls, Montana, United States
Mercy General Health Partners
🇺🇸Muskegon, Michigan, United States
CCOP - Grand Rapids
🇺🇸Grand Rapids, Michigan, United States
University of Mississippi Cancer Clinic
🇺🇸Jackson, Mississippi, United States
Bozeman Deaconess Cancer Center
🇺🇸Bozeman, Montana, United States
Northern Montana Hospital
🇺🇸Havre, Montana, United States
St. James Healthcare Cancer Care
🇺🇸Butte, Montana, United States
Glacier Oncology, PLLC
🇺🇸Kalispell, Montana, United States
St. Peter's Hospital
🇺🇸Helena, Montana, United States
Kalispell Regional Medical Center
🇺🇸Kalispell, Montana, United States
Kalispell Medical Oncology at KRMC
🇺🇸Kalispell, Montana, United States
Montana Cancer Specialists at Montana Cancer Center
🇺🇸Missoula, Montana, United States
CCOP - Upstate Carolina
🇺🇸Spartanburg, South Carolina, United States
U.T. Medical Center Cancer Institute
🇺🇸Knoxville, Tennessee, United States
Reid Hospital & Health Care Services
🇺🇸Richmond, Indiana, United States
Cardinal Bernardin Cancer Center at Loyola University Medical Center
🇺🇸Maywood, Illinois, United States
Grant Medical Center Cancer Care
🇺🇸Columbus, Ohio, United States
Wayne Memorial Hospital, Incorporated
🇺🇸Goldsboro, North Carolina, United States
Falck Cancer Center at Arnot Ogden Medical Center
🇺🇸Elmira, New York, United States
Mary Rutan Hospital
🇺🇸Bellefontaine, Ohio, United States
Wayne Hospital
🇺🇸Greenville, Ohio, United States
Grandview Hospital
🇺🇸Dayton, Ohio, United States
Good Samaritan Hospital
🇺🇸Dayton, Ohio, United States
Middletown Regional Hospital
🇺🇸Franklin, Ohio, United States
Community Hospital of Springfield and Clark County
🇺🇸Springfield, Ohio, United States
Skagit Valley Hospital Cancer Care Center
🇺🇸Mount Vernon, Washington, United States
Mount Carmel St. Ann's Cancer Center
🇺🇸Westerville, Ohio, United States
Genesis - Good Samaritan Hospital
🇺🇸Zanesville, Ohio, United States
Columbia Basin Hematology
🇺🇸Kennewick, Washington, United States
Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
🇺🇸Seattle, Washington, United States
Polyclinic First Hill
🇺🇸Seattle, Washington, United States
University Cancer Center at University of Washington Medical Center
🇺🇸Seattle, Washington, United States
Cancer Care Northwest - Spokane South
🇺🇸Spokane, Washington, United States
Wenatchee Valley Medical Center
🇺🇸Wenatchee, Washington, United States
Evergreen Hematology and Oncology, PS
🇺🇸Spokane, Washington, United States
Harrison Poulsbo Hematology and Onocology
🇺🇸Poulsbo, Washington, United States
Gibbs Regional Cancer Center at Spartanburg Regional Medical Center
🇺🇸Spartanburg, South Carolina, United States
Welch Cancer Center at Sheridan Memorial Hospital
🇺🇸Sheridan, Wyoming, United States
Olympic Hematology and Oncology
🇺🇸Bremerton, Washington, United States
St. Francis Hospital and Health Centers - Beech Grove Campus
🇺🇸Beech Grove, Indiana, United States