S0801 Iodine I 131 Tositumomab, Rituximab, and Combination Chemotherapy in Previously Untreated Stage II, Stage III, or Stage IV Follicular Non-Hodgkin Lymphoma

NCT ID: NCT00770224

Last Updated: 2019-08-28

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

87 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-04-30

Study Completion Date

2019-08-31

Brief Summary

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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

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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.

Conditions

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Lymphoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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R-CHOP, tositumomab and 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.

Group Type EXPERIMENTAL

rituximab

Intervention Type BIOLOGICAL

tositumomab

Intervention Type BIOLOGICAL

cyclophosphamide

Intervention Type DRUG

doxorubicin

Intervention Type DRUG

prednisone

Intervention Type DRUG

vincristine

Intervention Type DRUG

tositumomab

Intervention Type RADIATION

Interventions

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rituximab

Intervention Type BIOLOGICAL

tositumomab

Intervention Type BIOLOGICAL

cyclophosphamide

Intervention Type DRUG

doxorubicin

Intervention Type DRUG

prednisone

Intervention Type DRUG

vincristine

Intervention Type DRUG

tositumomab

Intervention Type RADIATION

Other Intervention Names

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iodine I 131 tositumomab

Eligibility Criteria

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Inclusion Criteria

DISEASE CHARACTERISTICS:

* Histologically confirmed\* grade 1, 2, or 3 follicular B-cell non-Hodgkin lymphoma meeting the following criteria:

* Bulky stage II or stage III or IV disease
* Diffuse large cell component must be \< 25% of the biopsy
* Confirmed cluster of differentiation antigen 20 (CD20) antigen-positive disease NOTE: \*Needle aspiration or cytology are not considered adequate for pathology review
* Patient must have unilateral or bilateral bone marrow aspirate and biopsy performed within 42 days

* Positive biopsy performed \> 42 days but \< 6 months allowed
* Previously untreated disease
* Bidimensionally measurable disease
* No clinical evidence of central nervous system (CNS) involvement by lymphoma

PATIENT CHARACTERISTICS:

* Zubrod performance status 0-2
* Cardiac ejection fraction ≥ 45% by multigated acquisition scan (MUGA) or ECHO
* No significant cardiac abnormalities
* No known HIV positivity
* No requirement for continuous supplemental oxygen therapy
* No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer from which the patient is currently in complete remission
* Not pregnant or nursing
* Fertile patients must use effective contraception during and for 12 months after completion of maintenance therapy

PRIOR CONCURRENT THERAPY:

* No prior chemotherapy, radiotherapy, or antibody therapy for lymphoma
* No prior solid organ transplantation
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

SWOG Cancer Research Network

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jonathan W. Friedberg, MD

Role: STUDY_CHAIR

James P. Wilmot Cancer Center

Oliver W. Press, MD, PhD

Role: STUDY_CHAIR

Fred Hutchinson Cancer Center

Lisa Rimsza, MD

Role: STUDY_CHAIR

University of Arizona

Locations

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Providence Cancer Center at Providence Hospital

Mobile, Alabama, United States

Site Status

Arizona Cancer Center at University of Arizona Health Sciences Center

Tucson, Arizona, United States

Site Status

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

Alton, Illinois, United States

Site Status

Cancer Care Center of Decatur

Decatur, Illinois, United States

Site Status

Decatur Memorial Hospital Cancer Care Institute

Decatur, Illinois, United States

Site Status

Crossroads Cancer Center

Effingham, Illinois, United States

Site Status

Cardinal Bernardin Cancer Center at Loyola University Medical Center

Maywood, Illinois, United States

Site Status

Good Samaritan Regional Health Center

Mount Vernon, Illinois, United States

Site Status

Regional Cancer Center at Memorial Medical Center

Springfield, Illinois, United States

Site Status

St. Francis Hospital and Health Centers - Beech Grove Campus

Beech Grove, Indiana, United States

Site Status

Reid Hospital & Health Care Services

Richmond, Indiana, United States

Site Status

Cancer Center of Kansas, PA - Chanute

Chanute, Kansas, United States

Site Status

Cancer Center of Kansas, PA - Dodge City

Dodge City, Kansas, United States

Site Status

Cancer Center of Kansas, PA - El Dorado

El Dorado, Kansas, United States

Site Status

Cancer Center of Kansas - Fort Scott

Fort Scott, Kansas, United States

Site Status

Cancer Center of Kansas-Independence

Independence, Kansas, United States

Site Status

Cancer Center of Kansas, PA - Kingman

Kingman, Kansas, United States

Site Status

Lawrence Memorial Hospital

Lawrence, Kansas, United States

Site Status

Cancer Center of Kansas, PA - Newton

Newton, Kansas, United States

Site Status

Cancer Center of Kansas, PA - Parsons

Parsons, Kansas, United States

Site Status

Cancer Center of Kansas, PA - Pratt

Pratt, Kansas, United States

Site Status

Cancer Center of Kansas, PA - Salina

Salina, Kansas, United States

Site Status

Tammy Walker Cancer Center at Salina Regional Health Center

Salina, Kansas, United States

Site Status

Cotton-O'Neil Cancer Center

Topeka, Kansas, United States

Site Status

Cancer Center of Kansas, PA - Wellington

Wellington, Kansas, United States

Site Status

Associates in Womens Health, PA - North Review

Wichita, Kansas, United States

Site Status

Cancer Center of Kansas, PA - Medical Arts Tower

Wichita, Kansas, United States

Site Status

Cancer Center of Kansas, PA - Wichita

Wichita, Kansas, United States

Site Status

CCOP - Wichita

Wichita, Kansas, United States

Site Status

Via Christi Cancer Center at Via Christi Regional Medical Center

Wichita, Kansas, United States

Site Status

Wesley Medical Center

Wichita, Kansas, United States

Site Status

Cancer Center of Kansas, PA - Winfield

Winfield, Kansas, United States

Site Status

Alvin and Lois Lapidus Cancer Institute at Sinai Hospital

Baltimore, Maryland, United States

Site Status

Battle Creek Health System Cancer Care Center

Battle Creek, Michigan, United States

Site Status

Mecosta County Medical Center

Big Rapids, Michigan, United States

Site Status

Butterworth Hospital at Spectrum Health

Grand Rapids, Michigan, United States

Site Status

CCOP - Grand Rapids

Grand Rapids, Michigan, United States

Site Status

Lacks Cancer Center at Saint Mary's Health Care

Grand Rapids, Michigan, United States

Site Status

Mercy General Health Partners

Muskegon, Michigan, United States

Site Status

Munson Medical Center

Traverse City, Michigan, United States

Site Status

Metro Health Hospital

Wyoming, Michigan, United States

Site Status

University of Mississippi Cancer Clinic

Jackson, Mississippi, United States

Site Status

Saint Francis Medical Center

Cape Girardeau, Missouri, United States

Site Status

Midwest Hematology Oncology Group, Incorporated

St Louis, Missouri, United States

Site Status

CCOP - St. Louis-Cape Girardeau

St Louis, Missouri, United States

Site Status

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

St Louis, Missouri, United States

Site Status

CCOP - Montana Cancer Consortium

Billings, Montana, United States

Site Status

St. Vincent Healthcare Cancer Care Services

Billings, Montana, United States

Site Status

Hematology-Oncology Centers of the Northern Rockies - Billings

Billings, Montana, United States

Site Status

Billings Clinic - Downtown

Billings, Montana, United States

Site Status

Bozeman Deaconess Cancer Center

Bozeman, Montana, United States

Site Status

St. James Healthcare Cancer Care

Butte, Montana, United States

Site Status

Great Falls Clinic - Main Facility

Great Falls, Montana, United States

Site Status

Sletten Cancer Institute at Benefis Healthcare

Great Falls, Montana, United States

Site Status

Northern Montana Hospital

Havre, Montana, United States

Site Status

St. Peter's Hospital

Helena, Montana, United States

Site Status

Glacier Oncology, PLLC

Kalispell, Montana, United States

Site Status

Kalispell Medical Oncology at KRMC

Kalispell, Montana, United States

Site Status

Kalispell Regional Medical Center

Kalispell, Montana, United States

Site Status

Montana Cancer Specialists at Montana Cancer Center

Missoula, Montana, United States

Site Status

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

Missoula, Montana, United States

Site Status

Falck Cancer Center at Arnot Ogden Medical Center

Elmira, New York, United States

Site Status

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

Rochester, New York, United States

Site Status

Wayne Memorial Hospital, Incorporated

Goldsboro, North Carolina, United States

Site Status

Rutherford Hospital

Rutherfordton, North Carolina, United States

Site Status

Mary Rutan Hospital

Bellefontaine, Ohio, United States

Site Status

Adena Regional Medical Center

Chillicothe, Ohio, United States

Site Status

Riverside Methodist Hospital Cancer Care

Columbus, Ohio, United States

Site Status

CCOP - Columbus

Columbus, Ohio, United States

Site Status

Grant Medical Center Cancer Care

Columbus, Ohio, United States

Site Status

Mount Carmel Health - West Hospital

Columbus, Ohio, United States

Site Status

Doctors Hospital at Ohio Health

Columbus, Ohio, United States

Site Status

Grandview Hospital

Dayton, Ohio, United States

Site Status

Good Samaritan Hospital

Dayton, Ohio, United States

Site Status

David L. Rike Cancer Center at Miami Valley Hospital

Dayton, Ohio, United States

Site Status

Samaritan North Cancer Care Center

Dayton, Ohio, United States

Site Status

CCOP - Dayton

Dayton, Ohio, United States

Site Status

Grady Memorial Hospital

Delaware, Ohio, United States

Site Status

Blanchard Valley Medical Associates

Findlay, Ohio, United States

Site Status

Middletown Regional Hospital

Franklin, Ohio, United States

Site Status

Wayne Hospital

Greenville, Ohio, United States

Site Status

Charles F. Kettering Memorial Hospital

Kettering, Ohio, United States

Site Status

Fairfield Medical Center

Lancaster, Ohio, United States

Site Status

Strecker Cancer Center at Marietta Memorial Hospital

Marietta, Ohio, United States

Site Status

Knox Community Hospital

Mount Vernon, Ohio, United States

Site Status

Licking Memorial Cancer Care Program at Licking Memorial Hospital

Newark, Ohio, United States

Site Status

Community Hospital of Springfield and Clark County

Springfield, Ohio, United States

Site Status

UVMC Cancer Care Center at Upper Valley Medical Center

Troy, Ohio, United States

Site Status

Mount Carmel St. Ann's Cancer Center

Westerville, Ohio, United States

Site Status

Clinton Memorial Hospital

Wilmington, Ohio, United States

Site Status

Ruth G. McMillan Cancer Center at Greene Memorial Hospital

Xenia, Ohio, United States

Site Status

Genesis - Good Samaritan Hospital

Zanesville, Ohio, United States

Site Status

AnMed Cancer Center

Anderson, South Carolina, United States

Site Status

CCOP - Upstate Carolina

Spartanburg, South Carolina, United States

Site Status

Gibbs Regional Cancer Center at Spartanburg Regional Medical Center

Spartanburg, South Carolina, United States

Site Status

U.T. Medical Center Cancer Institute

Knoxville, Tennessee, United States

Site Status

Huntsman Cancer Institute at University of Utah

Salt Lake City, Utah, United States

Site Status

St. Joseph Cancer Center

Bellingham, Washington, United States

Site Status

Olympic Hematology and Oncology

Bremerton, Washington, United States

Site Status

Columbia Basin Hematology

Kennewick, Washington, United States

Site Status

Skagit Valley Hospital Cancer Care Center

Mount Vernon, Washington, United States

Site Status

Harrison Poulsbo Hematology and Onocology

Poulsbo, Washington, United States

Site Status

Harborview Medical Center

Seattle, Washington, United States

Site Status

Minor and James Medical, PLLC

Seattle, Washington, United States

Site Status

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Site Status

Group Health Central Hospital

Seattle, Washington, United States

Site Status

Swedish Cancer Institute at Swedish Medical Center - First Hill Campus

Seattle, Washington, United States

Site Status

Polyclinic First Hill

Seattle, Washington, United States

Site Status

University Cancer Center at University of Washington Medical Center

Seattle, Washington, United States

Site Status

Cancer Care Northwest - Spokane South

Spokane, Washington, United States

Site Status

Evergreen Hematology and Oncology, PS

Spokane, Washington, United States

Site Status

Wenatchee Valley Medical Center

Wenatchee, Washington, United States

Site Status

Rocky Mountain Oncology

Casper, Wyoming, United States

Site Status

Welch Cancer Center at Sheridan Memorial Hospital

Sheridan, Wyoming, United States

Site Status

Countries

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United States

References

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Rutherford SC, Yin J, Pederson L, Perez Burbano G, LaPlant B, Shadman M, Li H, LeBlanc ML, Kenkre VP, Hong F, Blum KA, Dockter T, Martin P, Jung SH, Grant B, Rosenbaum C, Ujjani C, Barr PM, Unger JM, Cheson BD, Bartlett NL, Kahl B, Friedberg JW, Mandrekar SJ, Leonard JP. Relevance of Bone Marrow Biopsies for Response Assessment in US National Cancer Institute National Clinical Trials Network Follicular Lymphoma Clinical Trials. J Clin Oncol. 2023 Jan 10;41(2):336-342. doi: 10.1200/JCO.21.02301. Epub 2022 Jul 5.

Reference Type DERIVED
PMID: 35787017 (View on PubMed)

Barr PM, Li H, Burack WR, LeBlanc M, Smith SM, Gopal AK, Floyd JD, Persky DO, Press OW, Fisher RI, Friedberg JW. R-CHOP, radioimmunotherapy, and maintenance rituximab in untreated follicular lymphoma (SWOG S0801): a single-arm, phase 2, multicentre study. Lancet Haematol. 2018 Mar;5(3):e102-e108. doi: 10.1016/S2352-3026(18)30001-2. Epub 2018 Jan 26.

Reference Type DERIVED
PMID: 29396094 (View on PubMed)

Provided Documents

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Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Other Identifiers

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S0801

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA032102

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CDR0000615104

Identifier Type: -

Identifier Source: org_study_id

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