Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

Summary

RATIONALE: 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 work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving rituximab together with combination chemotherapy may kill more cancer cells. It is not yet known which combination chemotherapy regimen is more effective when given with rituximab in treating diffuse large B-cell non-Hodgkin's lymphoma. Imaging procedures, such as fludeoxyglucose F 18 positron emission tomography (FDG-PET)/computed tomography (CT), may help diagnose if recurrent disease is likely.

PURPOSE: This randomized phase III trial is studying rituximab when given together with two different combination chemotherapy regimens to compare how well they work in treating patients with diffuse large B-cell non-Hodgkin's lymphoma.

Further Study Information

OBJECTIVES:

Primary

• 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.

• Determine molecular predictors of outcome (using molecular profiling) in patients treated with these regimens.

Secondary

• Compare the response rate and overall survival of patients treated with these regimens.

• Compare the toxicity of these regimens in these patients.

• Correlate the clinical parameters (i.e., toxicity, response, survival outcomes, and laboratory results) with molecular profiling in patients treated with these regimens.

• Assess the use of molecular profiling for pathological diagnosis in patients treated with these regimens.

• Identify new therapeutic targets using molecular profiling.

• Perform a comprehensive analysis of somatic alterations to the tumor genome in order to understand which genomic alterations are somatically acquired by the tumor and which are encoded in the germ line of the patient.

• Identify biomarkers of response to chemotherapy by FDG-PET/CT imaging that are predictive of histopathologic remissions and survival in patients with stage I (mediastinal), II, III, or IV untreated DLBCL.

• Evaluate the use of semiquantitative measurements of FDG uptake in defining FDG-PET/CT-based biomarkers of response to chemotherapy in patients with DLBCL.

• Determine whether FDG-PET/CT measurements of tumor response after the second cycle of chemotherapy can predict clinical response.

• Establish a standardized protocol for FDG-PET/CT image acquisition.

• Determine additional FDG-PET/CT parameters (e.g., the ratio of tumor SUVmax to liver SUVmean; SUVs corrected for body surface area and lean body mass; nuclear medicine physician's assessment) and evaluate their utility in refining FDG-PET/CT based biomarkers of response to therapy.

• Evaluate inter-institutional reproducibility of FDG-PET/CT measurements for this indication.

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.

As of July 1, 2012, the FDG-PET/CT imaging companion study CALGB-580603 will be required of all patients enrolling on this study. FDG-PET/CT scans of abdomen/chest/pelvis are collected at baseline, post-course 2, and post-course 6.

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

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

Eligibility 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

• As of July 1, 2012, the PET/CT imaging companion study CALGB-580603 will be required of all patients enrolling onto the treatment study CALGB-50303 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.

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

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

Trial Contact Information

Trial Lead Organizations/Sponsors

Cancer and Leukemia Group B

Wyndham Hopkins Wilson

Study Chair

Andrew D. Zelenetz

U.S.A.
California
	Mountain View
	Palo Alto Medical Foundation
		Peter P. Yu	Ph: 650-934-7000
	Palo Alto
	Palo Alto Medical Foundation
		David S Leibowitz	Ph: 650-853-2906
			Email: waldorj@pamf.org
	Saint Helena
	Saint Helena Hospital
		Gregory B Smith	Ph: 707-967-3698
	San Diego
	Naval Medical Center - San Diego
		Preston S. Gable	Ph: 619-532-8712
	Rebecca and John Moores UCSD Cancer Center
		Erin G Reid	Ph: 858-822-5354
			Email: cancercto@ucsd.edu
Connecticut
	Norwich
	Eastern Connecticut Hematology and Oncology Associates
		Dennis E. Slater	Ph: 860-886-8362
Delaware
	Lewes
	Tunnell Cancer Center at Beebe Medical Center
		Stephen Scott Grubbs	Ph: 302-733-6227
	Newark
	Helen F. Graham Cancer Center at Christiana Hospital
		Stephen Scott Grubbs	Ph: 302-733-6227
Illinois
	Chicago
	Cancer and Leukemia Group B
		Wyndham H Wilson	Ph: 301-435-2415
			Email: wilsonw@mail.nih.gov
	Creticos Cancer Center at Advocate Illinois Masonic Medical Center
		Deepti A. Singh	Ph: 773-296-5360
	Mount Sinai Hospital Medical Center
		Pam G. Khosla	Ph: 773-257-5960
			Email: suhi@sinai.org
	Robert H. Lurie Comprehensive Cancer Center at Northwestern University
		Jane N. Winter	Ph: 312-695-1301
			Email: cancer@northwestern.edu
	University of Illinois Cancer Center
		David J. Peace	Ph: 312-355-3046
	Maywood
	Cardinal Bernardin Cancer Center at Loyola University Medical Center
		Scott E. Smith	Ph: 708-226-4357
Maryland
	Baltimore
	Alvin and Lois Lapidus Cancer Institute at Sinai Hospital
		Roberto F Martinez	Ph: 410-601-6120
			Email: pridgely@lifebridgehealth.org
	Bethesda
	National Institutes of Health
		Wyndham Hopkins Wilson	Ph: 800-411-1222
	National Naval Medical Center
		David C Van Echo	Ph: 301-319-2100
Michigan
	Southfield
	Providence Hospital - Southfield
		Howard R. Terebelo	Ph: 248-849-5337
			Email: jaswinder.grewal@stjohn.org
Missouri
	Saint Louis
	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
		Nancy L. Bartlett	Ph: 800-600-3606
			Email: info@siteman.wustl.edu
New Hampshire
	Concord
	New Hampshire Oncology - Hematology, PA at Payson Center for Cancer Care
		Douglas Jay Weckstein	Ph: 603-224-2556
	Hooksett
	New Hampshire Oncology - Hematology, PA - Hooksett
		Douglas Jay Weckstein	Ph: 603-224-2556
New Jersey
	Newark
	UMDNJ University Hospital
		Lillian F. Pliner	Ph: 732-235-8675
New York
	Glens Falls
	Charles R. Wood Cancer Center at Glens Falls Hospital
		Aqeel A Gillani	Ph: 518-926-6700
	New York
	New York Weill Cornell Cancer Center at Cornell University
		John P. Leonard	Ph: 212-746-1848
	Rochester
	James P. Wilmot Cancer Center at University of Rochester Medical Center
		Jonathan W Friedberg	Ph: 585-275-5830
North Carolina
	Charlotte
	Presbyterian Cancer Center at Presbyterian Hospital
		Justin P Favaro	Ph: 704-384-5369
	Kinston
	Kinston Medical Specialists
		Peter R. Watson	Ph: 252-559-2200
	Statesville
	Iredell Memorial Hospital
		Ruby A. Grimm	Ph: 704-873-5661
	Winston-Salem
	Wake Forest University Comprehensive Cancer Center
		David Duane Hurd	Ph: 336-713-6771
North Dakota
	Grand Forks
	Altru Cancer Center at Altru Hospital
		Grant R Seeger	Ph: 701-780-6520
Ohio
	Canton
	Mercy Cancer Center at Mercy Medical Center
		Mitchell Haut	Ph: 888-293-4673
	Columbus
	Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center
		Kristie A. Blum	Ph: 866-627-7616
			Email: osu@emergingmed.com
Pennsylvania
	Danville
	Geisinger Cancer Institute at Geisinger Health
		Edward J Gorak	Ph: 570-271-5251
	Easton
	Easton Regional Cancer Center at Easton Hospital
		Rajen P Oza	Ph: 610-250-4000
	Hazleton
	Geisinger Hazleton Cancer Center
		Edward J Gorak	Ph: 570-271-5251
	Hershey
	Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center
		Elliot M. Epner	Ph: 717-531-3779
			Email: CTO@hmc.psu.edu
	Pittsburgh
	Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital
		John Lister	Ph: 412-578-5000
	Wilkes-Barre
	Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center
		Edward J Gorak	Ph: 570-271-5251
Texas
	Amarillo
	Harrington Cancer Center
		Stewart Allen Sharp	Ph: 806-359-4673
			Email: ryokubaitis@harringtoncc.org
Vermont
	Berlin
	Mountainview Medical
		Emiliano N Mugnaini	Ph: 802-656-8990
Washington
	Tacoma
	Madigan Army Medical Center - Tacoma
		Anthony J Fadell	Ph: 253-968-0129
			Email: mamcdci@amedd.army.mil
West Virginia
	Morgantown
	Mary Babb Randolph Cancer Center at West Virginia University Hospitals
		Sayed M Hamadani	Ph: 304-293-2745
			Email: sfilburn@hsc.wvu.edu
Wisconsin
	Marshfield
	Marshfield Clinic - Marshfield Center
		Ali W. Bseiso	Ph: 715-389-4457
	Saint Joseph's Hospital
		Ali W. Bseiso	Ph: 715-389-4457
	Minocqua
	Marshfield Clinic - Lakeland Center
		Ali W. Bseiso	Ph: 715-389-4457
	Rhinelander
	Ministry Medical Group at Saint Mary's Hospital
		Ali W. Bseiso	Ph: 715-389-4457
	Rice Lake
	Marshfield Clinic - Indianhead Center
		Ali W. Bseiso	Ph: 715-389-4457
	Stevens Point
	Marshfield Clinic at Saint Michael's Hospital
		Ali W. Bseiso	Ph: 715-389-4457
	Saint Michael's Hospital Cancer Center
		Ali W. Bseiso	Ph: 715-389-4457
	Weston
	Diagnostic and Treatment Center
		Ali W. Bseiso	Ph: 715-389-4457
	Marshfield Clinic - Weston Center
		Ali W. Bseiso	Ph: 715-389-4457

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00118209
Information obtained from ClinicalTrials.gov on February 14, 2013

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