Clinical trial NCT00107380: 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
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lymphoma
Keywords: 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
Lead sponsor: SWOG Cancer Research Network
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2005-04-06
Enrollment: 86
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Progression-free Survival (PFS) at 2 Years
timeFrame: 0-2 years
measure: Response Rate (Complete, Complete Unconfirmed, and Partial)
timeFrame: 6 months
Secondary outcomes:
measure: Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug
timeFrame: 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)
Other outcomes:
Locations:
city: Anchorage
country: United States
facility: Alaska Regional Hospital Cancer Center
state: Alaska
city: Tucson
country: United States
facility: Arizona Cancer Center at University of Arizona Health Sciences Center
state: Arizona
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Atlanta
country: United States
facility: Piedmont Hospital
state: Georgia
city: Atlanta
country: United States
facility: Northside Hospital Cancer Center
state: Georgia
city: Atlanta
country: United States
facility: Saint Joseph's Hospital of Atlanta
state: Georgia
city: Atlanta
country: United States
facility: CCOP - Atlanta Regional
state: Georgia
city: Austell
country: United States
facility: WellStar Cobb Hospital
state: Georgia
city: Decatur
country: United States
facility: Charles B. Eberhart Cancer Center at DeKalb Medical Center
state: Georgia
city: Lawrenceville
country: United States
facility: Gwinnett Medical Center
state: Georgia
city: Marietta
country: United States
facility: Kennestone Cancer Center at Wellstar Kennestone Hospital
state: Georgia
city: Riverdale
country: United States
facility: Southern Regional Medical Center
state: Georgia
city: Rome
country: United States
facility: Harbin Clinic Cancer Center - Medical Oncology
state: Georgia
city: Alton
country: United States
facility: Saint Anthony's Hospital at Saint Anthony's Health Center
state: Illinois
city: Maywood
country: United States
facility: Cardinal Bernardin Cancer Center at Loyola University Medical Center
state: Illinois
city: Mt. Vernon
country: United States
facility: Good Samaritan Regional Health Center
state: Illinois
city: Beech Grove
country: United States
facility: St. Francis Hospital and Health Centers - Beech Grove Campus
state: Indiana
city: Richmond
country: United States
facility: Reid Hospital & Health Care Services
state: Indiana
city: Topeka
country: United States
facility: Cotton-O'Neil Cancer Center
state: Kansas
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Cape Girardeau
country: United States
facility: Saint Francis Medical Center
state: Missouri
city: Saint Louis
country: United States
facility: Midwest Hematology Oncology Group, Incorporated
state: Missouri
city: Saint Louis
country: United States
facility: CCOP - St. Louis-Cape Girardeau
state: Missouri
city: Saint Louis
country: United States
facility: David C. Pratt Cancer Center at St. John's Mercy
state: Missouri
city: Billings
country: United States
facility: CCOP - Montana Cancer Consortium
state: Montana
city: Billings
country: United States
facility: Hematology-Oncology Centers of the Northern Rockies - Billings
state: Montana
city: Billings
country: United States
facility: Northern Rockies Radiation Oncology Center
state: Montana
city: Billings
country: United States
facility: St. Vincent Healthcare Cancer Care Services
state: Montana
city: Billings
country: United States
facility: Billings Clinic - Downtown
state: Montana
city: Bozeman
country: United States
facility: Bozeman Deaconess Cancer Center
state: Montana
city: Butte
country: United States
facility: St. James Healthcare Cancer Care
state: Montana
city: Great Falls
country: United States
facility: Big Sky Oncology
state: Montana
city: Great Falls
country: United States
facility: Great Falls Clinic - Main Facility
state: Montana
city: Great Falls
country: United States
facility: Sletten Cancer Institute at Benefis Healthcare
state: Montana
city: Great Falls
country: United States
state: Montana
city: Havre
country: United States
facility: Northern Montana Hospital
state: Montana
city: Helena
country: United States
facility: St. Peter's Hospital
state: Montana
city: Kalispell
country: United States
facility: Glacier Oncology, PLLC
state: Montana
city: Kalispell
country: United States
facility: Kalispell Medical Oncology at KRMC
state: Montana
city: Kalispell
country: United States
facility: Kalispell Regional Medical Center
state: Montana
city: Missoula
country: United States
facility: Community Medical Center
state: Montana
city: Missoula
country: United States
facility: Guardian Oncology and Center for Wellness
state: Montana
city: Missoula
country: United States
facility: Montana Cancer Specialists at Montana Cancer Center
state: Montana
city: Missoula
country: United States
facility: Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
state: Montana
city: Elmira
country: United States
facility: Falck Cancer Center at Arnot Ogden Medical Center
state: New York
city: Rochester
country: United States
facility: James P. Wilmot Cancer Center at University of Rochester Medical Center
state: New York
city: Rutherfordton
country: United States
facility: Rutherford Hospital
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Dayton
country: United States
facility: Grandview Hospital
state: Ohio
city: Dayton
country: United States
facility: Good Samaritan Hospital
state: Ohio
city: Dayton
country: United States
facility: David L. Rike Cancer Center at Miami Valley Hospital
state: Ohio
city: Dayton
country: United States
facility: Samaritan North Cancer Care Center
state: Ohio
city: Dayton
country: United States
facility: CCOP - Dayton
state: Ohio
city: Findlay
country: United States
facility: Blanchard Valley Medical Associates
state: Ohio
city: Franklin
country: United States
facility: Middletown Regional Hospital
state: Ohio
city: Greenville
country: United States
facility: Wayne Hospital
state: Ohio
city: Independence
country: United States
facility: Cleveland Clinic Cancer Center
state: Ohio
city: Kettering
country: United States
facility: Charles F. Kettering Memorial Hospital
state: Ohio
city: Troy
country: United States
facility: UVMC Cancer Care Center at Upper Valley Medical Center
state: Ohio
city: Wilmington
country: United States
facility: Clinton Memorial Hospital
state: Ohio
city: Wooster
country: United States
facility: Cleveland Clinic - Wooster
state: Ohio
city: Xenia
country: United States
facility: Ruth G. McMillan Cancer Center at Greene Memorial Hospital
state: Ohio
city: Anderson
country: United States
facility: AnMed Cancer Center
state: South Carolina
city: Spartanburg
country: United States
facility: CCOP - Upstate Carolina
state: South Carolina
city: Spartanburg
country: United States
facility: Gibbs Regional Cancer Center at Spartanburg Regional Medical Center
state: South Carolina
city: Bellingham
country: United States
facility: St. Joseph Cancer Center
state: Washington
city: Bremerton
country: United States
facility: Olympic Hematology and Oncology
state: Washington
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Seattle
country: United States
facility: Harborview Medical Center
state: Washington
city: Seattle
country: United States
facility: Minor and James Medical, PLLC
state: Washington
city: Seattle
country: United States
facility: Group Health Central Hospital
state: Washington
city: Seattle
country: United States
facility: Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
state: Washington
city: Seattle
country: United States
facility: Polyclinic First Hill
state: Washington
city: Seattle
country: United States
facility: University Cancer Center at University of Washington Medical Center
state: Washington
city: Spokane
country: United States
facility: Cancer Care Northwest - Spokane South
state: Washington
city: Spokane
country: United States
facility: Evergreen Hematology and Oncology, PS
state: Washington
city: Casper
country: United States
facility: Rocky Mountain Oncology
state: Wyoming
city: Sheridan
country: United States
facility: Welch Cancer Center at Sheridan Memorial Hospital
state: Wyoming
Study officials:
affiliation: James P. Wilmot Cancer Center
name: Jonathan W. Friedberg, MD
role: STUDY_CHAIR
affiliation: James P. Wilmot Cancer Center
name: Richard I. Fisher, MD
role: STUDY_DIRECTOR
References: