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
- Conditions
- Lymphoma
- Interventions
- Biological: rituximabRadiation: tositumomab and iodine I 131 tositumomab
- Registration Number
- NCT00107380
- 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 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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 86
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description R-CHOP x 8 with I-131 Tositumomab 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 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 R-CHOP x 8 with I-131 Tositumomab tositumomab and iodine 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 R-CHOP x 8 with I-131 Tositumomab vincristine sulfate 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 R-CHOP x 8 with I-131 Tositumomab 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 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 R-CHOP x 8 with I-131 Tositumomab doxorubicin hydrochloride 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 R-CHOP x 8 with I-131 Tositumomab 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 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
- Primary Outcome Measures
Name Time Method 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.
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
Name Time Method 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.
Trial Locations
- Locations (77)
CCOP - Montana Cancer Consortium
🇺🇸Billings, Montana, United States
Hematology-Oncology Centers of the Northern Rockies - Billings
🇺🇸Billings, Montana, United States
Northern Rockies Radiation Oncology Center
🇺🇸Billings, Montana, United States
Kalispell Regional Medical Center
🇺🇸Kalispell, Montana, United States
Billings Clinic - Downtown
🇺🇸Billings, Montana, United States
St. Peter's Hospital
🇺🇸Helena, Montana, United States
Northern Montana Hospital
🇺🇸Havre, Montana, United States
Saint Francis Medical Center
🇺🇸Cape Girardeau, Missouri, United States
Midwest Hematology Oncology Group, Incorporated
🇺🇸Saint Louis, Missouri, United States
CCOP - Atlanta Regional
🇺🇸Atlanta, Georgia, United States
CCOP - St. Louis-Cape Girardeau
🇺🇸Saint Louis, Missouri, United States
Charles B. Eberhart Cancer Center at DeKalb Medical Center
🇺🇸Decatur, Georgia, United States
Kennestone Cancer Center at Wellstar Kennestone Hospital
🇺🇸Marietta, Georgia, United States
Saint Anthony's Hospital at Saint Anthony's Health Center
🇺🇸Alton, Illinois, United States
CCOP - Upstate Carolina
🇺🇸Spartanburg, South Carolina, United States
Gwinnett Medical Center
🇺🇸Lawrenceville, Georgia, United States
Clinton Memorial Hospital
🇺🇸Wilmington, Ohio, United States
David C. Pratt Cancer Center at St. John's Mercy
🇺🇸Saint Louis, Missouri, United States
CCOP - Dayton
🇺🇸Dayton, Ohio, United States
Group Health Central Hospital
🇺🇸Seattle, Washington, United States
Rutherford Hospital
🇺🇸Rutherfordton, North Carolina, United States
James P. Wilmot Cancer Center at University of Rochester Medical Center
🇺🇸Rochester, New York, United States
University Cancer Center at University of Washington Medical Center
🇺🇸Seattle, Washington, United States
Samaritan North Cancer Care Center
🇺🇸Dayton, Ohio, United States
Cleveland Clinic Cancer Center
🇺🇸Independence, Ohio, United States
David L. Rike Cancer Center at Miami Valley Hospital
🇺🇸Dayton, Ohio, United States
Falck Cancer Center at Arnot Ogden Medical Center
🇺🇸Elmira, New York, United States
Ruth G. McMillan Cancer Center at Greene Memorial Hospital
🇺🇸Xenia, Ohio, United States
Cardinal Bernardin Cancer Center at Loyola University Medical Center
🇺🇸Maywood, Illinois, United States
Big Sky Oncology
🇺🇸Great Falls, Montana, United States
Great Falls Clinic - Main Facility
🇺🇸Great Falls, Montana, United States
Sletten Cancer Institute at Benefis Healthcare
🇺🇸Great Falls, Montana, United States
Glacier Oncology, PLLC
🇺🇸Kalispell, Montana, United States
Kalispell Medical Oncology at KRMC
🇺🇸Kalispell, Montana, United States
Community Medical Center
🇺🇸Missoula, Montana, United States
Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
🇺🇸Missoula, Montana, United States
Wayne Hospital
🇺🇸Greenville, Ohio, United States
Charles F. Kettering Memorial Hospital
🇺🇸Kettering, Ohio, United States
UVMC Cancer Care Center at Upper Valley Medical Center
🇺🇸Troy, Ohio, United States
Gibbs Regional Cancer Center at Spartanburg Regional Medical Center
🇺🇸Spartanburg, South Carolina, United States
Harborview Medical Center
🇺🇸Seattle, Washington, United States
Polyclinic First Hill
🇺🇸Seattle, Washington, United States
Cotton-O'Neil Cancer Center
🇺🇸Topeka, Kansas, United States
Rocky Mountain Oncology
🇺🇸Casper, Wyoming, United States
Welch Cancer Center at Sheridan Memorial Hospital
🇺🇸Sheridan, Wyoming, United States
Olympic Hematology and Oncology
🇺🇸Bremerton, Washington, United States
Arizona Cancer Center at University of Arizona Health Sciences Center
🇺🇸Tucson, Arizona, United States
Cancer Care Northwest - Spokane South
🇺🇸Spokane, Washington, United States
Saint Joseph's Hospital of Atlanta
🇺🇸Atlanta, Georgia, United States
WellStar Cobb Hospital
🇺🇸Austell, Georgia, United States
Southern Regional Medical Center
🇺🇸Riverdale, Georgia, United States
St. Francis Hospital and Health Centers - Beech Grove Campus
🇺🇸Beech Grove, Indiana, United States
Minor and James Medical, PLLC
🇺🇸Seattle, Washington, United States
Reid Hospital & Health Care Services
🇺🇸Richmond, Indiana, United States
Middletown Regional Hospital
🇺🇸Franklin, Ohio, United States
Blanchard Valley Medical Associates
🇺🇸Findlay, Ohio, United States
St. Joseph Cancer Center
🇺🇸Bellingham, Washington, United States
Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
🇺🇸Seattle, Washington, United States
Evergreen Hematology and Oncology, PS
🇺🇸Spokane, Washington, United States
Alaska Regional Hospital Cancer Center
🇺🇸Anchorage, Alaska, United States
Piedmont Hospital
🇺🇸Atlanta, Georgia, United States
Northside Hospital Cancer Center
🇺🇸Atlanta, Georgia, United States
City of Hope Comprehensive Cancer Center
🇺🇸Duarte, California, United States
Harbin Clinic Cancer Center - Medical Oncology
🇺🇸Rome, Georgia, United States
Good Samaritan Regional Health Center
🇺🇸Mt. Vernon, Illinois, United States
St. Vincent Healthcare Cancer Care Services
🇺🇸Billings, Montana, United States
Bozeman Deaconess Cancer Center
🇺🇸Bozeman, Montana, United States
St. James Healthcare Cancer Care
🇺🇸Butte, Montana, United States
Montana Cancer Specialists at Montana Cancer Center
🇺🇸Missoula, Montana, United States
Guardian Oncology and Center for Wellness
🇺🇸Missoula, Montana, United States
Good Samaritan Hospital
🇺🇸Dayton, Ohio, United States
Cleveland Clinic Taussig Cancer Center
🇺🇸Cleveland, Ohio, United States
Grandview Hospital
🇺🇸Dayton, Ohio, United States
Cleveland Clinic - Wooster
🇺🇸Wooster, Ohio, United States
AnMed Cancer Center
🇺🇸Anderson, South Carolina, United States
Fred Hutchinson Cancer Research Center
🇺🇸Seattle, Washington, United States
University of Michigan Comprehensive Cancer Center
🇺🇸Ann Arbor, Michigan, United States