Combination Chemotherapy With or Without Monoclonal Antibody Therapy in Treating Older Patients With Non-Hodgkin's Lymphoma

NCT ID: NCT00003150

Last Updated: 2013-06-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

630 participants

Study Classification

INTERVENTIONAL

Study Start Date

1997-12-31

Study Completion Date

2006-09-30

Brief Summary

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RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies such as rituximab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. It is not yet known if combination chemotherapy is more effective with or without rituximab for non-Hodgkin's lymphoma.

PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy with or without rituximab in treating older patients who have non-Hodgkin's lymphoma.

Detailed Description

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OBJECTIVES: I. Compare the efficacy of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) with or without rituximab in older patients with diffuse mixed, diffuse large, or immunoblastic large cell non-Hodgkin's lymphoma of B-cell lineage with respect to the response rate, time to treatment failure, toxicity, and survival. II. Compare the efficacy of maintenance therapy consisting of rituximab vs observation alone after initial therapy with respect to the time to treatment failure, duration of response, toxicity, and survival of this patient population. III. Determine if maintenance therapy with rituximab results in the conversion of any partial response to complete response.

OUTLINE: This is a randomized study. For the first randomization, patients are stratified according to the number of risk factors (0-1 vs 2-4). For the second randomization, in addition to the number of risk factors, patients are stratified according to objective response to initial induction therapy (partial response vs complete response) and induction therapy (CHOP vs CHOP and rituximab). Patients are randomized to one of two treatment arms. Arm I: Patients receive CHOP chemotherapy comprising cyclophosphamide IV, doxorubicin IV, and vincristine IV on day 1 and oral prednisone on days 1-5. Treatment repeats every 21 days in the absence of unacceptable toxicity. Arm II: Patients receive treatment as in arm I. Patients also receive rituximab IV on days -7,-3, 41, and 83. Patients who achieve complete response (CR) after 4 courses of CHOP and remain in CR after 6 courses of CHOP are further randomized to one of two arms. Arm I (Maintenance therapy): Patients receive rituximab IV weekly for 4 weeks. Courses repeat every 6 months for 2 years in the absence of unacceptable toxicity. Arm II: Patients are observed. Patients who achieve partial response (PR) after 6 courses OR PR after 4 courses and then CR after 6 courses receive 2 additional courses of CHOP therapy. Patients are then also randomized to receive either maintenance therapy or observation as above. Patients with stable disease or disease progression are removed from the study. Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: Approximately 630 patients will be accrued for this study within 4 years.

Conditions

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Lymphoma

Study Design

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Allocation Method

RANDOMIZED

Primary Study Purpose

TREATMENT

Interventions

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rituximab

Intervention Type BIOLOGICAL

CHOP regimen

Intervention Type DRUG

cyclophosphamide

Intervention Type DRUG

doxorubicin hydrochloride

Intervention Type DRUG

prednisone

Intervention Type DRUG

vincristine sulfate

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

PATIENT CHARACTERISTICS: Age: See Disease Characteristics 60 and over Performance status: ECOG 0-3 Life expectancy: Not specified Hematopoietic: Absolute granulocyte count at least 1,500/mm3 (unless due to lymphoma) Platelet count greater than 100,000/mm3 (unless due to lymphoma) Hepatic: Bilirubin no greater than 3.0 mg/dL Renal: Creatinine less than 2.1 mg/dL OR Creatinine clearance at least 60 mL/min Cardiovascular: No active heart disease including congestive heart failure, myocardial infarction within the past 3 months, or symptomatic ventricular arrhythmia LVEF at least 45% if prior history of heart disease exists Other: HIV negative No other malignancy within the past 5 years except squamous cell or basal cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY: Biologic therapy: See Disease Characteristics No prior biologic response modifier therapy No prior immunotherapy No prior rituximab Chemotherapy: No prior cytotoxic chemotherapy No concurrent dexrazoxane Endocrine therapy: Prior corticosteroids allowed Radiotherapy: No prior radiotherapy No prior radioimmunotherapy Surgery: Not specified
Minimum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Cancer and Leukemia Group B

NETWORK

Sponsor Role collaborator

SWOG Cancer Research Network

NETWORK

Sponsor Role collaborator

Eastern Cooperative Oncology Group

NETWORK

Sponsor Role lead

Principal Investigators

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Thomas M. Habermann, MD

Role: STUDY_CHAIR

Mayo Clinic

Vicki A. Morrison, MD

Role: STUDY_CHAIR

Veterans Affairs Medical Center - Minneapolis

James K. Weick, MD

Role: STUDY_CHAIR

Hematology Oncology Associates of the Palm Beaches

Locations

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MBCCOP - Gulf Coast

Mobile, Alabama, United States

Site Status

CCOP - Greater Phoenix

Phoenix, Arizona, United States

Site Status

Veterans Affairs Medical Center - Phoenix (Hayden)

Phoenix, Arizona, United States

Site Status

Veterans Affairs Medical Center - Tucson

Tucson, Arizona, United States

Site Status

Arizona Cancer Center

Tucson, Arizona, United States

Site Status

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status

Veterans Affairs Medical Center - Little Rock (McClellan)

Little Rock, Arkansas, United States

Site Status

Cancer Center and Beckman Research Institute, City of Hope

Duarte, California, United States

Site Status

Veterans Affairs Medical Center - Long Beach

Long Beach, California, United States

Site Status

USC/Norris Comprehensive Cancer Center and Hospital

Los Angeles, California, United States

Site Status

Veterans Affairs Medical Center - West Los Angeles

Los Angeles, California, United States

Site Status

Jonsson Comprehensive Cancer Center, UCLA

Los Angeles, California, United States

Site Status

Veterans Affairs Outpatient Clinic - Martinez

Martinez, California, United States

Site Status

CCOP - Bay Area Tumor Institute

Oakland, California, United States

Site Status

Chao Family Comprehensive Cancer Center

Orange, California, United States

Site Status

University of California Davis Medical Center

Sacramento, California, United States

Site Status

CCOP - Santa Rosa Memorial Hospital

Santa Rosa, California, United States

Site Status

David Grant Medical Center

Travis Air Force Base, California, United States

Site Status

University of Colorado Cancer Center

Denver, Colorado, United States

Site Status

Veterans Affairs Medical Center - Denver

Denver, Colorado, United States

Site Status

Hematology Oncology Associates

Atlantis, Florida, United States

Site Status

CCOP - Atlanta Regional

Atlanta, Georgia, United States

Site Status

Dwight David Eisenhower Army Medical Center

Fort Gordon, Georgia, United States

Site Status

Cancer Research Center of Hawaii

Honolulu, Hawaii, United States

Site Status

MBCCOP - University of Illinois at Chicago

Chicago, Illinois, United States

Site Status

CCOP - Central Illinois

Decatur, Illinois, United States

Site Status

Veterans Affairs Medical Center - Hines (Hines Junior VA Hospital)

Hines, Illinois, United States

Site Status

Loyola University Medical Center

Maywood, Illinois, United States

Site Status

University of Kansas Medical Center

Kansas City, Kansas, United States

Site Status

CCOP - Wichita

Wichita, Kansas, United States

Site Status

Veterans Affairs Medical Center - Wichita

Wichita, Kansas, United States

Site Status

Veterans Affairs Medical Center - Lexington

Lexington, Kentucky, United States

Site Status

Albert B. Chandler Medical Center, University of Kentucky

Lexington, Kentucky, United States

Site Status

MBCCOP - LSU Health Sciences Center

New Orleans, Louisiana, United States

Site Status

Tulane University School of Medicine

New Orleans, Louisiana, United States

Site Status

Louisiana State University Health Sciences Center - Shreveport

Shreveport, Louisiana, United States

Site Status

Veterans Affairs Medical Center - Shreveport

Shreveport, Louisiana, United States

Site Status

Boston Medical Center

Boston, Massachusetts, United States

Site Status

Veterans Affairs Medical Center - Boston (Jamaica Plain)

Jamaica Plain, Massachusetts, United States

Site Status

Veterans Affairs Medical Center - Ann Arbor

Ann Arbor, Michigan, United States

Site Status

CCOP - Ann Arbor Regional

Ann Arbor, Michigan, United States

Site Status

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Site Status

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Veterans Affairs Medical Center - Detroit

Detroit, Michigan, United States

Site Status

Henry Ford Hospital

Detroit, Michigan, United States

Site Status

CCOP - Grand Rapids Clinical Oncology Program

Grand Rapids, Michigan, United States

Site Status

Providence Hospital - Southfield

Southfield, Michigan, United States

Site Status

CCOP - Duluth

Duluth, Minnesota, United States

Site Status

Veterans Affairs Medical Center - Biloxi

Biloxi, Mississippi, United States

Site Status

University of Mississippi Medical Center

Jackson, Mississippi, United States

Site Status

Veterans Affairs Medical Center - Jackson

Jackson, Mississippi, United States

Site Status

Keesler Medical Center - Keesler AFB

Keesler Air Force Base, Mississippi, United States

Site Status

Veterans Affairs Medical Center - Kansas City

Kansas City, Missouri, United States

Site Status

CCOP - Kansas City

Kansas City, Missouri, United States

Site Status

CCOP - Cancer Research for the Ozarks

Springfield, Missouri, United States

Site Status

St. Louis University Health Sciences Center

St Louis, Missouri, United States

Site Status

CCOP - St. Louis-Cape Girardeau

St Louis, Missouri, United States

Site Status

CCOP - Montana Cancer Consortium

Billings, Montana, United States

Site Status

Veterans Affairs Medical Center - Albuquerque

Albuquerque, New Mexico, United States

Site Status

MBCCOP - University of New Mexico HSC

Albuquerque, New Mexico, United States

Site Status

Herbert Irving Comprehensive Cancer Center

New York, New York, United States

Site Status

CCOP - Southeast Cancer Control Consortium

Winston-Salem, North Carolina, United States

Site Status

Barrett Cancer Center, The University Hospital

Cincinnati, Ohio, United States

Site Status

Veterans Affairs Medical Center - Cincinnati

Cincinnati, Ohio, United States

Site Status

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, United States

Site Status

CCOP - Columbus

Columbus, Ohio, United States

Site Status

Veterans Affairs Medical Center - Dayton

Dayton, Ohio, United States

Site Status

CCOP - Dayton

Kettering, Ohio, United States

Site Status

CCOP - Toledo Community Hospital Oncology Program

Toledo, Ohio, United States

Site Status

Veterans Affairs Medical Center - Oklahoma City

Oklahoma City, Oklahoma, United States

Site Status

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status

Oregon Cancer Center

Portland, Oregon, United States

Site Status

Veterans Affairs Medical Center - Portland

Portland, Oregon, United States

Site Status

CCOP - Columbia River Program

Portland, Oregon, United States

Site Status

CCOP - Greenville

Greenville, South Carolina, United States

Site Status

CCOP - Upstate Carolina

Spartanburg, South Carolina, United States

Site Status

Simmons Cancer Center - Dallas

Dallas, Texas, United States

Site Status

Brooke Army Medical Center

Fort Sam Houston, Texas, United States

Site Status

University of Texas Medical Branch

Galveston, Texas, United States

Site Status

Texas Tech University Health Science Center

Lubbock, Texas, United States

Site Status

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Site Status

Veterans Affairs Medical Center - San Antonio (Murphy)

San Antonio, Texas, United States

Site Status

Veterans Affairs Medical Center - Temple

Temple, Texas, United States

Site Status

CCOP - Scott and White Hospital

Temple, Texas, United States

Site Status

Huntsman Cancer Institute

Salt Lake City, Utah, United States

Site Status

Veterans Affairs Medical Center - Salt Lake City

Salt Lake City, Utah, United States

Site Status

CCOP - Virginia Mason Research Center

Seattle, Washington, United States

Site Status

Swedish Cancer Institute

Seattle, Washington, United States

Site Status

Veterans Affairs Medical Center - Seattle

Seattle, Washington, United States

Site Status

CCOP - Northwest

Tacoma, Washington, United States

Site Status

Madigan Army Medical Center

Tacoma, Washington, United States

Site Status

Countries

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United States

References

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Advani RH, Chen H, Habermann TM, Morrison VA, Weller EA, Fisher RI, Peterson BA, Gascoyne RD, Horning SJ; Eastern Cooperative Oncology Group; Cancer and Leukemia Group B; Southwest Oncology Group. Comparison of conventional prognostic indices in patients older than 60 years with diffuse large B-cell lymphoma treated with R-CHOP in the US Intergroup Study (ECOG 4494, CALGB 9793): consideration of age greater than 70 years in an elderly prognostic index (E-IPI). Br J Haematol. 2010 Oct;151(2):143-51. doi: 10.1111/j.1365-2141.2010.08331.x.

Reference Type RESULT
PMID: 20735398 (View on PubMed)

Winter JN, Li S, Aurora V, Variakojis D, Nelson B, Krajewska M, Zhang L, Habermann TM, Fisher RI, Macon WR, Chhanabhai M, Felgar RE, Hsi ED, Medeiros LJ, Weick JK, Weller EA, Melnick A, Reed JC, Horning SJ, Gascoyne RD. Expression of p21 protein predicts clinical outcome in DLBCL patients older than 60 years treated with R-CHOP but not CHOP: a prospective ECOG and Southwest Oncology Group correlative study on E4494. Clin Cancer Res. 2010 Apr 15;16(8):2435-42. doi: 10.1158/1078-0432.CCR-09-1219. Epub 2010 Apr 6.

Reference Type RESULT
PMID: 20371683 (View on PubMed)

Aurora V, Li S, Horning SJ, et al.: Prognostic significance of p53/p21 expression in DLBCL treated with CHOP or R-CHOP: a correlative study of E4494. [Abstract] J Clin Oncol 25 (Suppl 18): A-8038, 450s, 2007.

Reference Type RESULT

Morrison VA, Weller EA, Habermann TM, et al.: Maintenance rituximab (MR) compared to observation (OBS) after R-CHOP or CHOP in older patients (pts) with diffuse large B-cell lymphoma (DLBCL): an Intergroup E4494/C9793 update. [Abstract] J Clin Oncol 25 (Suppl 18): A-8011, 443s, 2007.

Reference Type RESULT

Advani RH, Chen H, Habermann TM, et al.: Prognostic indices in older DLBCL patients receiving R-CHOP: an analysis of the U.S. Intergroup study (E4494, CALGB 9793). [Abstract] Blood 108 (11): A-813, 2006.

Reference Type RESULT

Habermann TM, Weller EA, Morrison VA, Gascoyne RD, Cassileth PA, Cohn JB, Dakhil SR, Woda B, Fisher RI, Peterson BA, Horning SJ. Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma. J Clin Oncol. 2006 Jul 1;24(19):3121-7. doi: 10.1200/JCO.2005.05.1003. Epub 2006 Jun 5.

Reference Type RESULT
PMID: 16754935 (View on PubMed)

Winter JN, Weller EA, Horning SJ, Krajewska M, Variakojis D, Habermann TM, Fisher RI, Kurtin PJ, Macon WR, Chhanabhai M, Felgar RE, Hsi ED, Medeiros LJ, Weick JK, Reed JC, Gascoyne RD. Prognostic significance of Bcl-6 protein expression in DLBCL treated with CHOP or R-CHOP: a prospective correlative study. Blood. 2006 Jun 1;107(11):4207-13. doi: 10.1182/blood-2005-10-4222. Epub 2006 Jan 31.

Reference Type RESULT
PMID: 16449523 (View on PubMed)

Morrison V, Weller E, Habermann T, et al.: Dose intensity of CHOP alone or with rituximab in diffuse large B-cell lymphoma (DLBCL) in patients >60 years of age: an analysis of the intergroup trial ( CALGB 9793, ECOG-SWOG 4494). [Abstract] Ann Oncol 16 (Suppl 5): A-224, v102, 2005.

Reference Type RESULT

Habermann TM, Weller E, Morrison VA, et al.: Rituximab-CHOP versus CHOP with or without maintenance rituximab in patients 60 years of age or older with diffuse large B-cell lymphoma (DLBCL): an update. [Abstract] Blood 104 (11): A-127, 2004.

Reference Type RESULT

Morrison VA, Weller EA, Habermann TM, Li S, Fisher RI, Cheson BD, Peterson BA. Patterns of growth factor usage and febrile neutropenia among older patients with diffuse large B-cell non-Hodgkin lymphoma treated with CHOP or R-CHOP: the Intergroup experience (CALGB 9793; ECOG-SWOG 4494). Leuk Lymphoma. 2017 Aug;58(8):1814-1822. doi: 10.1080/10428194.2016.1265111. Epub 2016 Dec 14.

Reference Type RESULT
PMID: 27967294 (View on PubMed)

Other Identifiers

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ECOG-E4494

Identifier Type: -

Identifier Source: secondary_id

CLB-9793

Identifier Type: -

Identifier Source: secondary_id

SWOG-E4494

Identifier Type: -

Identifier Source: secondary_id

CDR0000065935

Identifier Type: -

Identifier Source: org_study_id

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