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

NCT ID: NCT00107380

Last Updated: 2016-03-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 86 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-11-30
• Study Completion Date: 2015-12-31

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.

Conditions

Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

rituximab

Intervention Type: BIOLOGICAL

cyclophosphamide

Intervention Type: DRUG

doxorubicin hydrochloride

Intervention Type: DRUG

prednisone

Intervention Type: DRUG

vincristine sulfate

Intervention Type: DRUG

tositumomab and iodine I 131 tositumomab

Intervention Type: RADIATION

Interventions

rituximab

Intervention Type: BIOLOGICAL

cyclophosphamide

Intervention Type: DRUG

doxorubicin hydrochloride

Intervention Type: DRUG

prednisone

Intervention Type: DRUG

vincristine sulfate

Intervention Type: DRUG

tositumomab and iodine I 131 tositumomab

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

SWOG Cancer Research Network

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jonathan W. Friedberg, MD

Role: STUDY_CHAIR

James P. Wilmot Cancer Center

Richard I. Fisher, MD

Role: STUDY_DIRECTOR

James P. Wilmot Cancer Center

Locations

Alaska Regional Hospital Cancer Center

Anchorage, Alaska, United States

Arizona Cancer Center at University of Arizona Health Sciences Center

Tucson, Arizona, United States

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Piedmont Hospital

Atlanta, Georgia, United States

Northside Hospital Cancer Center

Atlanta, Georgia, United States

Saint Joseph's Hospital of Atlanta

Atlanta, Georgia, United States

CCOP - Atlanta Regional

Atlanta, Georgia, United States

WellStar Cobb Hospital

Austell, Georgia, United States

Charles B. Eberhart Cancer Center at DeKalb Medical Center

Decatur, Georgia, United States

Gwinnett Medical Center

Lawrenceville, Georgia, United States

Kennestone Cancer Center at Wellstar Kennestone Hospital

Marietta, Georgia, United States

Southern Regional Medical Center

Riverdale, Georgia, United States

Harbin Clinic Cancer Center - Medical Oncology

Rome, Georgia, United States

Saint Anthony's Hospital at Saint Anthony's Health Center

Alton, Illinois, United States

Cardinal Bernardin Cancer Center at Loyola University Medical Center

Maywood, Illinois, United States

Good Samaritan Regional Health Center

Mount Vernon, Illinois, United States

St. Francis Hospital and Health Centers - Beech Grove Campus

Beech Grove, Indiana, United States

Reid Hospital & Health Care Services

Richmond, Indiana, United States

Cotton-O'Neil Cancer Center

Topeka, Kansas, United States

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Saint Francis Medical Center

Cape Girardeau, Missouri, United States

Midwest Hematology Oncology Group, Incorporated

St Louis, Missouri, United States

CCOP - St. Louis-Cape Girardeau

St Louis, Missouri, United States

David C. Pratt Cancer Center at St. John's Mercy

St Louis, Missouri, United States

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

St. Vincent Healthcare Cancer Care Services

Billings, Montana, United States

Billings Clinic - Downtown

Billings, Montana, United States

Bozeman Deaconess Cancer Center

Bozeman, Montana, United States

St. James Healthcare Cancer Care

Butte, Montana, 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

Great Falls, Montana, United States

Northern Montana Hospital

Havre, Montana, United States

St. Peter's Hospital

Helena, Montana, United States

Glacier Oncology, PLLC

Kalispell, Montana, United States

Kalispell Medical Oncology at KRMC

Kalispell, Montana, United States

Kalispell Regional Medical Center

Kalispell, Montana, United States

Community Medical Center

Missoula, Montana, United States

Guardian Oncology and Center for Wellness

Missoula, Montana, United States

Montana Cancer Specialists at Montana Cancer Center

Missoula, Montana, United States

Montana Cancer Center at St. Patrick Hospital and Health Sciences Center

Missoula, Montana, United States

Falck Cancer Center at Arnot Ogden Medical Center

Elmira, New York, United States

James P. Wilmot Cancer Center at University of Rochester Medical Center

Rochester, New York, United States

Rutherford Hospital

Rutherfordton, North Carolina, United States

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, United States

Grandview Hospital

Dayton, Ohio, United States

Good Samaritan Hospital

Dayton, Ohio, United States

David L. Rike Cancer Center at Miami Valley Hospital

Dayton, Ohio, United States

Samaritan North Cancer Care Center

Dayton, Ohio, United States

CCOP - Dayton

Dayton, Ohio, United States

Blanchard Valley Medical Associates

Findlay, Ohio, United States

Middletown Regional Hospital

Franklin, Ohio, United States

Wayne Hospital

Greenville, Ohio, United States

Cleveland Clinic Cancer Center

Independence, 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

Clinton Memorial Hospital

Wilmington, Ohio, United States

Cleveland Clinic - Wooster

Wooster, Ohio, United States

Ruth G. McMillan Cancer Center at Greene Memorial Hospital

Xenia, Ohio, United States

AnMed Cancer Center

Anderson, South Carolina, United States

CCOP - Upstate Carolina

Spartanburg, South Carolina, United States

Gibbs Regional Cancer Center at Spartanburg Regional Medical Center

Spartanburg, South Carolina, United States

St. Joseph Cancer Center

Bellingham, Washington, United States

Olympic Hematology and Oncology

Bremerton, Washington, United States

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Harborview Medical Center

Seattle, Washington, United States

Minor and James Medical, PLLC

Seattle, Washington, United States

Group Health Central Hospital

Seattle, 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

Evergreen Hematology and Oncology, PS

Spokane, Washington, United States

Rocky Mountain Oncology

Casper, Wyoming, United States

Welch Cancer Center at Sheridan Memorial Hospital

Sheridan, Wyoming, United States

Countries

United States

Other Identifiers

S0433

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA032102

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CDR0000415955

Identifier Type: -

Identifier Source: org_study_id