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

Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00107380
• Other study ID #: CDR0000415955
• Secondary ID: S0433U10CA032102
• Status: Completed
• Phase: Phase 2
• First received: April 5, 2005
• Last updated: February 4, 2016
• Start date: November 2005
• Est. completion date: December 2015

Study information

• Verified date: February 2016
• Source: Southwest Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 86
• Est. completion date: December 2015
• Est. primary completion date: November 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 120 Years

Eligibility

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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma

Intervention

Biological:
• rituximab

Drug:
• cyclophosphamide

• doxorubicin hydrochloride

• prednisone

• vincristine sulfate

Radiation:
• tositumomab and iodine I 131 tositumomab

Locations

Country	Name	City	State
United States	Saint Anthony's Hospital at Saint Anthony's Health Center	Alton	Illinois
United States	Alaska Regional Hospital Cancer Center	Anchorage	Alaska
United States	AnMed Cancer Center	Anderson	South Carolina
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	CCOP - Atlanta Regional	Atlanta	Georgia
United States	Northside Hospital Cancer Center	Atlanta	Georgia
United States	Piedmont Hospital	Atlanta	Georgia
United States	Saint Joseph's Hospital of Atlanta	Atlanta	Georgia
United States	WellStar Cobb Hospital	Austell	Georgia
United States	St. Francis Hospital and Health Centers - Beech Grove Campus	Beech Grove	Indiana
United States	St. Joseph Cancer Center	Bellingham	Washington
United States	Billings Clinic - Downtown	Billings	Montana
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	Bozeman Deaconess Cancer Center	Bozeman	Montana
United States	Olympic Hematology and Oncology	Bremerton	Washington
United States	St. James Healthcare Cancer Care	Butte	Montana
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Rocky Mountain Oncology	Casper	Wyoming
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	CCOP - Dayton	Dayton	Ohio
United States	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio
United States	Good Samaritan Hospital	Dayton	Ohio
United States	Grandview Hospital	Dayton	Ohio
United States	Samaritan North Cancer Care Center	Dayton	Ohio
United States	Charles B. Eberhart Cancer Center at DeKalb Medical Center	Decatur	Georgia
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Falck Cancer Center at Arnot Ogden Medical Center	Elmira	New York
United States	Blanchard Valley Medical Associates	Findlay	Ohio
United States	Middletown Regional Hospital	Franklin	Ohio
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	Wayne Hospital	Greenville	Ohio
United States	Northern Montana Hospital	Havre	Montana
United States	St. Peter's Hospital	Helena	Montana
United States	Cleveland Clinic Cancer Center	Independence	Ohio
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	Charles F. Kettering Memorial Hospital	Kettering	Ohio
United States	Gwinnett Medical Center	Lawrenceville	Georgia
United States	Kennestone Cancer Center at Wellstar Kennestone Hospital	Marietta	Georgia
United States	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois
United States	Community Medical Center	Missoula	Montana
United States	Guardian Oncology and Center for Wellness	Missoula	Montana
United States	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana
United States	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana
United States	Good Samaritan Regional Health Center	Mt. Vernon	Illinois
United States	Reid Hospital & Health Care Services	Richmond	Indiana
United States	Southern Regional Medical Center	Riverdale	Georgia
United States	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York
United States	Harbin Clinic Cancer Center - Medical Oncology	Rome	Georgia
United States	Rutherford Hospital	Rutherfordton	North Carolina
United States	CCOP - St. Louis-Cape Girardeau	Saint Louis	Missouri
United States	David C. Pratt Cancer Center at St. John's Mercy	Saint Louis	Missouri
United States	Midwest Hematology Oncology Group, Incorporated	Saint Louis	Missouri
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Group Health Central Hospital	Seattle	Washington
United States	Harborview Medical Center	Seattle	Washington
United States	Minor and James Medical, PLLC	Seattle	Washington
United States	Polyclinic First Hill	Seattle	Washington
United States	Swedish Cancer Institute at Swedish Medical Center - First Hill Campus	Seattle	Washington
United States	University Cancer Center at University of Washington Medical Center	Seattle	Washington
United States	Welch Cancer Center at Sheridan Memorial Hospital	Sheridan	Wyoming
United States	CCOP - Upstate Carolina	Spartanburg	South Carolina
United States	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina
United States	Cancer Care Northwest - Spokane South	Spokane	Washington
United States	Evergreen Hematology and Oncology, PS	Spokane	Washington
United States	Cotton-O'Neil Cancer Center	Topeka	Kansas
United States	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio
United States	Arizona Cancer Center at University of Arizona Health Sciences Center	Tucson	Arizona
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

Sponsors (2)

Lead Sponsor	Collaborator
Southwest Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival (PFS) at 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.	0-2 years	No
Primary	Response Rate (Complete, Complete Unconfirmed, and Partial)	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.	6 months	No
Secondary	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 3.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal.	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)	Yes