Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Related Information
Registry Information

Alternate Title

Rituximab and Combination Chemotherapy in Treating Patients With Diffuse Large B-Cell Non-Hodgkin's Lymphoma

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Active 18 and over NCI CALGB-50303 CALGB-50303, ECOG-50303, NCI-05-C-0252, NCT00118209

Special Category: NIH Clinical Center trial

Objectives

Primary

1. Compare the event-free survival of patients with previously untreated de novo diffuse large B-cell non-Hodgkin's lymphoma treated with R-CHOP comprising rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone vs EPOCH-R comprising etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab.
2. Determine molecular predictors of outcome (using molecular profiling) in patients treated with these regimens.

Secondary

1. Compare the response rate and overall survival of patients treated with these regimens.
2. Compare the toxicity of these regimens in these patients.
3. Correlate the clinical parameters (i.e., toxicity, response, survival outcomes, and laboratory results) with molecular profiling in patients treated with these regimens.
4. Determine the use of molecular profiling for pathological diagnosis in patients treated with these regimens.

Entry Criteria

Disease Characteristics:

• Histologically confirmed* de novo B-cell non-Hodgkin's lymphoma (NHL) of 1 of the following WHO histologic subtypes:
  • Diffuse large cell lymphoma, including any of the following morphologic variants:
    • Centroblastic
    • Immunoblastic
    • T-cell/histiocyte rich
    • Anaplastic
  • Mediastinal (thymic) large cell lymphoma
  • Intravascular large cell lymphoma

   [Note: *Fine needle aspirates or core biopsies must not be the only diagnostic material]




• Stage I primary mediastinal (thymic) OR stage II-IV disease



• CD20-positive disease



• No underlying low-grade lymphoma (e.g., transformed lymphoma or low-grade lymphoma in the bone marrow)



• No known lymphomatous CNS involvement
  • Lumbar puncture required unless there are no neurological symptoms

 [Note: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.]

Prior/Concurrent Therapy:

Biologic therapy

• No prior rituximab

Chemotherapy

• No prior chemotherapy for other malignancies
• No prior cytotoxic chemotherapy
• No other concurrent chemotherapy

Endocrine therapy

• Prior short course (< 10 days) glucocorticoids allowed for an urgent local disease complication (e.g., cord compression or superior vena cava syndrome) at diagnosis
• No concurrent hormonal therapy except steroids for adrenal failure or hormones for non-disease related conditions (e.g., insulin for diabetes)
• No concurrent dexamethasone or other steroidal antiemetics

Radiotherapy

• Prior limited field radiotherapy allowed for an urgent local disease complication (e.g., cord compression or superior vena cava syndrome) at diagnosis
• No concurrent radiotherapy except for isolated CNS lesions

Surgery

• Not specified

Other

• No other concurrent investigational or commercial agents or therapies for NHL

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,000/mm^3*
• Platelet count ≥ 100,000/mm^3*
• No active bleeding unrelated to NHL

 [Note: *Unless due to NHL]

Hepatic

• Bilirubin ≤ 2 mg/dL*

 [Note: *Unless due to NHL or Gilbert's disease]

Renal

• Creatinine ≤ 1.5 mg/dL^*

  OR

• Creatinine clearance ≥ 50 mL/min^*

 [Note: *Unless due to NHL]

Cardiovascular

• No active ischemic heart disease
• No congestive heart failure

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• HIV negative
• No active uncontrolled bacterial or viral infection unrelated to NHL
• No other active medical process unrelated to NHL

Expected Enrollment

A total of 478 patients (239 per treatment arm) will be accrued for this study within 4.5 years.

Outcomes

Event-free survival 5 years after completion of study treatment

R-CHOP and DA-EPOCH-R molecular predictors of outcome as measured by cDNA microarray 5 years after completion of study treatment

Outline

This is a randomized, multicenter study. Patients are stratified according to International Prognostic Index score. Patients are randomized to 1 of 2 treatment arms.

• Arm I (R-CHOP): Patients receive rituximab IV, cyclophosphamide IV, doxorubicin IV over 3-5 minutes, and vincristine IV on day 1 and oral prednisone once daily on days 1-5. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.



• Arm II (EPOCH-R): Patients receive rituximab IV on day 1, doxorubicin IV, etoposide IV, and vincristine IV continuously over 96 hours on days 1-4, cyclophosphamide IV on day 5, and oral prednisone twice daily on days 1-5. Patients also receive filgrastim (G-CSF) once daily on days 2-11 or until blood counts recover. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for up to 3 years.

Trial Contact Information

Trial Lead Organizations

Cancer and Leukemia Group B

Wyndham Wilson, MD, PhD, Protocol chair		Ph: 301-435-2415 Email: wilsonw@mail.nih.gov
Andrew D. Zelenetz, MD, PhD, Protocol co-chair		Ph: 212-639-2656; 800-525-2225

U.S.A.
Alabama
	Anniston
	Regional Medical Center
		Ellen Spremulli	Ph:  256-235-5877
Alaska
	Anchorage
	Providence Cancer Center
		Clinical Trials Office - Providence Cancer Center	Ph:  907-261-3109
California
	Burbank
	Providence Saint Joseph Medical Center - Burbank
		Clinical Trials Office - Providence Saint Joseph Medical Center - Burbank	Ph:  818-847-3220
	Mountain View
	Camino Medical Group - Treatment Center
		Peter Yu, MD	Ph:  408-524-5085
	Orange
	St. Joseph Hospital Regional Cancer Center - Orange
		Tiberio Lindgren	Ph:  714-771-8999
	Palm Springs
	Desert Regional Medical Center Comprehensive Cancer Center
		Clinical Trials Office - Desert Regional Medical Center Comprehensive Cancer Center	Ph:  760-416-4730
	Palo Alto
	Palo Alto Medical Foundation
		Peter Yu, MD	Ph:  408-524-5085
	Sacramento
	University of California Davis Cancer Center
		Clinical Trials Office - University of California Davis Cancer Center	Ph:  916-734-3089
	San Diego
	Naval Medical Center - San Diego
		Preston Gable, MD, FACP	Ph:  619-532-7303
	San Francisco
	UCSF Helen Diller Family Comprehensive Cancer Center
		Clinical Trials Office - UCSF Helen Diller Family Comprehensive Cancer Center	Ph:  877-827-3222
Colorado
	Colorado Springs
	Memorial Hospital Cancer Center - Colorado Springs
		Clinical Trials Office - Memorial Hospital	Ph:  719-365-2406
	Fort Collins
	Front Range Cancer Specialists
		Diana Medgyesy, MD	Ph:  970-212-7600
	Poudre Valley Hospital
		Clinical Trials Office - Poudre Valley Hospital	Ph:  970-495-8226
Connecticut
	Farmington
	Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center
		Clinical Trials Office - Carole and Ray Neag Comprehensive Cancer Center	Ph:  800-579-7822
	Hartford
	Helen and Harry Gray Cancer Center at Hartford Hospital
		Clinical Trials Office - Helen and Harry Gray Cancer Center	Ph:  860-545-5363
	Norwich
	Eastern Connecticut Hematology and Oncology Associates
		Dennis Slater, MD	Ph:  860-886-8362
Delaware
	Lewes
	Tunnell Cancer Center at Beebe Medical Center
		Clinical Trials Office - Tunnell Cancer Center	Ph:  302-645-3171
	Newark
	CCOP - Christiana Care Health Services
		Clinical Trial Office - CCOP - Christiana Care Health Services	Ph:  302-733-6227
District of Columbia
	Washington
	Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
		Clinical Trials Office - Lombardi Comprehensive Cancer Center	Ph:  202-444-0381
	Sibley Memorial Hospital
		Bruce Kressel, MD, FACP	Ph:  202-537-4000
	Walter Reed Army Medical Center
		Clinical Trials Office - Walter Reed Army Medical Center	Ph:  202-782-7840
Florida
	Fort Lauderdale
	Michael and Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital
		Clinical Trials Office - Michael and Dianne Bienes Comprehensive Cancer Center	Ph:  954-776-3239
	Jupiter
	Ella Milbank Foshay Cancer Center at Jupiter Medical Center
		Clinical Trials Office - Ella Milbank Foshay Cancer Center	Ph:  561-745-5768
	Weston
	Cleveland Clinic Florida - Weston
		Clinical Trials Office - Cleveland Clinic Florida - Weston	Ph:  954-659-5705
Georgia
	Augusta
	Augusta Oncology Associates - Walton Way
		Mark Keaton, MD	Ph:  706-821-2944
	Columbus
	John B. Amos Cancer Center
		Clinical Trials Office - John B. Amos Cancer Center	Ph:  706-660-6404
	Macon
	Medical Center of Central Georgia
		Frederick Schnell, MD, FACP	Ph:  478-743-7068
Illinois
	Aurora
	Rush-Copley Cancer Care Center
		Kendrith Rowland, MD	Ph:  217-383-3010
	Chicago
	Hematology and Oncology Associates
		Clinical Trails Office - Hematology and Oncology Associates	Ph:  312-695-1301
	Robert H. Lurie Comprehensive Cancer Center at Northwestern University
		Clinical Trials Office - Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Ph:  312-695-1301
			Email: cancer@northwestern.edu
	University of Chicago Cancer Research Center
		Clinical Trials Office - University of Chicago Cancer Research Center	Ph:  773-834-7424
	Joliet
	Joliet Oncology-Hematology Associates, Limited - West
		Sanjiv Modi	Ph:  815-730-3098
	Midwest Center for Hematology/Oncology
		Jane Winter, MD	Ph:  312-695-6180
	Libertyville
	North Shore Oncology and Hematology Associates, Limited - Libertyville
		Jane Winter, MD	Ph:  312-695-6180
	Maywood
	Cardinal Bernardin Cancer Center at Loyola University Medical Center
		Clinical Trials Office - Cardinal Bernardin Cancer Center	Ph:  708-226-4357
	Niles
	Cancer Care and Hematology Specialists of Chicagoland - Niles
		Jane Winter, MD	Ph:  312-695-6180
	Olympia Fields
	Saint James Hospital and Health Centers Comprehensive Cancer Institute - Olympia Fields
		Clinical Trials Office - Saint James Hospital and Health Centers Comprehensive Cancer Institute - Olympia Fields	Ph:  708-679-2217
	Skokie
	Hematology Oncology Associates - Skokie
		Jane Winter, MD	Ph:  312-695-6180
	Urbana
	Carle Cancer Center at Carle Foundation Hospital
		Clinical Trials Office - Carle Cancer Center	Ph:  800-446-5532
	CCOP - Carle Cancer Center
		Clinical Trials Office - CCOP - Carle Cancer Center	Ph:  800-446-5532
Indiana
	Fort Wayne
	Fort Wayne Medical Oncology and Hematology
		Sreenivasa Nattam, MD	Ph:  260-484-8830 800-852-2333
	Michigan City
	Saint Anthony Memorial Health Centers
		Kendrith Rowland, MD	Ph:  217-383-3010
	Munster
	Community Hospital
		Erwin Robin, MD	Ph:  219-836-4503
Iowa
	Ames
	McFarland Clinic, PC
		Clinical Trials Office - McFarland Clinic, PC	Ph:  515-239-2621
	Cedar Rapids
	Cedar Rapids Oncology Associates
		Clinical Trials Office - Cedar Rapids Oncology Associates	Ph:  319-363-2690
	Sioux City
	Mercy Medical Center - Sioux City
		Donald Wender, MD, PhD	Ph:  712-252-9326
	Siouxland Hematology-Oncology Associates, LLP
		Donald Wender, MD, PhD	Ph:  712-252-9326
	St. Luke's Regional Medical Center
		Donald Wender, MD, PhD	Ph:  712-252-9326
Kansas
	Topeka
	Cotton-O'Neil Cancer Center
		Clinical Trials Office - Cotton-O'Neil Cancer Center	Ph:  785-270-4963
Kentucky
	Louisville
	James Graham Brown Cancer Center at University of Louisville
		Roger Herzig	Ph:  502-562-4158 866-530-5516
Maine
	Waterville
	MaineGeneral Medical Center - Waterville
		Clinical Trials Office - MaineGeneral Medical Center - Waterville	Ph:  207-872-1792
Maryland
	Baltimore
	Alvin and Lois Lapidus Cancer Institute at Sinai Hospital
		Stephen J. Noga, MD, PhD	Ph:  410-601-4734
	Greenebaum Cancer Center at University of Maryland Medical Center
		Clinical Trials Office - Greenebaum Cancer Center at University of Maryladn Medical Center	Ph:  800-888-8823
	Bethesda
	NIH - Warren Grant Magnuson Clinical Center
		Clinical Trials Office - NIH - Warren Grant Magnuson Clinical Center	Ph:  800-411-1222
	Elkton MD
	Union Hospital Cancer Program at Union Hospital
		Stephen Grubbs, MD	Ph:  410-398-4000
	Kensington
	Associates in Oncology and Hematology
		Paul Thambi	Ph:  301-929-0765
	Rockville
	Associates in Oncology and Hematology - Medical Center Drive
		Paul Thambi	Ph:  301-424-6231
Massachusetts
	Boston
	Massachusetts General Hospital
		Clinical Trials Office - Massachusetts General Hospital	Ph:  877-726-5130
Michigan
	Battle Creek
	Battle Creek Health System Cancer Care Center
		Marianne Lange, MD	Ph:  616-966-8000
	Big Rapids
	Mecosta County Medical Center
		Marianne Lange, MD	Ph:  231-796-8691
	Escanaba
	Green Bay Oncology, Limited - Escanaba
		Thomas Saphner, MD, FACP	Ph:  800-432-6049
	Grand Rapids
	Butterworth Hospital at Spectrum Health
		Marianne Lange, MD	Ph:  616-391-2799
	CCOP - Grand Rapids
		Marianne Lange, MD	Ph:  616-391-1230
	Lacks Cancer Center at Saint Mary's Health Care
		Marianne Lange, MD	Ph:  616-752-5222
	Holland
	Holland Community Hospital
		Marianne Lange, MD	Ph:  616-392-5141
	Iron Mountain
	Dickinson County Healthcare System
		Thomas Saphner, MD, FACP	Ph:  906-774-1313
	Kalamazoo
	Borgess Medical Center
		Raymond Lord, MD	Ph:  269-373-7488
	Bronson Methodist Hospital
		Raymond Lord, MD	Ph:  269-373-7488
	West Michigan Cancer Center
		Clinical Trials Office - West Michigan Cancer Center	Ph:  269-373-7458
	Muskegon
	Hackley Hospital
		Marianne Lange, MD	Ph:  231-726-3511
	Southfield
	Providence Cancer Institute at Providence Hospital - Southfield Campus
		Howard Terebelo, DO	Ph:  248-552-0620
	Traverse City
	Munson Medical Center
		Marianne Lange, MD	Ph:  231-935-6202
	Wyoming
	Metro Health Hospital
		Marianne Lange, MD	Ph:  616-252-7200
Minnesota
	Minneapolis
	Veterans Affairs Medical Center - Minneapolis
		Clinical Trials Office - Veterans Affairs Medical Center - Minneapolis	Ph:  612-467-2800
Missouri
	Saint Louis
	Christian Hospital Northeast Cancer Care Center
		Timothy Rearden, MD	Ph:  314-653-5733
	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
		Nancy Bartlett, MD	Ph:  314-362-4843
Montana
	Billings
	Billings Clinic - Downtown
		Clinical Trials Office - Billings Clinic - Downtown	Ph:  800-996-2663
			Email: research@billingsclinic.org
	CCOP - Montana Cancer Consortium
		Benjamin Marchello, MD	Ph:  406-259-2245 800-361-3239
	Hematology-Oncology Centers of the Northern Rockies - Billings
		Benjamin Marchello, MD	Ph:  406-238-6290 800-648-6274
	Northern Rockies Radiation Oncology Center
		Benjamin Marchello, MD	Ph:  406-248-2212 800-358-8818
	St. Vincent Healthcare Cancer Care Services
		Benjamin Marchello, MD	Ph:  406-657-7000
	Bozem