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
	Northridge
	Northridge Hospital Medical Center
		Sheldon J. Davidson	Ph: 818-885-5458
	San Diego
	Rebecca and John Moores UCSD Cancer Center
		Erin G Reid	Ph: 858-822-5354
			Email: cancercto@ucsd.edu
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
Georgia
	Albany
	Phoebe Cancer Center at Phoebe Putney Memorial Hospital
		Jose M. Tongol	Ph: 229-312-2251
	Savannah
	Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/Candler
		O. George Negrea	Ph: 912-350-8568
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
	Louis A. Weiss Memorial Hospital
		Keith L. Shulman	Ph: 773-564-5044
Louisiana
	Baton Rouge
	Ochsner Health Center - Bluebonnet
		Charles V Wendling	Ph: 888-562-4763
	Covington
	Ochsner Health Center - Covington
		Charles V Wendling	Ph: 888-562-4763
	New Orleans
	CCOP - Ochsner
		Charles V Wendling	Ph: 888-562-4763
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
Mississippi
	Jackson
	University of Mississippi Cancer Clinic
		Vincent E Herrin	Ph: 601-815-6700
Missouri
	Saint Louis
	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
		Nancy L. Bartlett	Ph: 800-600-3606
			Email: info@siteman.wustl.edu
Montana
	Great Falls
	Big Sky Oncology
		Grant William Harrer	Ph: 406-731-8217
New Jersey
	Newark
	UMDNJ University Hospital
		Lillian F. Pliner	Ph: 732-235-8675
	Paterson
	St. Joseph's Hospital and Medical Center
		Michael Maroules	Ph: 973-754-2909
New York
	Glens Falls
	Charles R. Wood Cancer Center at Glens Falls Hospital
		Aqeel A Gillani	Ph: 518-926-6700
North Carolina
	Kinston
	Kinston Medical Specialists
		Peter R. Watson	Ph: 252-559-2200
	Winston-Salem
	Wake Forest University Comprehensive Cancer Center
		David Duane Hurd	Ph: 336-713-6771
Ohio
	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
	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
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
	Centralia
	Providence Centralia Hospital
		Yoshio Inoue	Ph: 253-403-2394
	Federal Way
	St. Francis Hospital
		Yoshio Inoue	Ph: 253-403-2394
	Olympia
	Providence St. Peter Hospital Regional Cancer Center
		Yoshio Inoue	Ph: 253-403-2394
	Puyallup
	Good Samaritan Cancer Center
		Yoshio Inoue	Ph: 253-403-2394
	Tacoma
	Allenmore Hospital
		Yoshio Inoue	Ph: 253-403-2394
	CCOP - Northwest
		Yoshio Inoue	Ph: 253-403-2394
	Franciscan Cancer Center at St. Joseph Medical Center
		Yoshio Inoue	Ph: 253-403-2394
	MultiCare Regional Cancer Center at Tacoma General Hospital
		Yoshio Inoue	Ph: 253-403-2394
	St. Clare Hospital
		Yoshio Inoue	Ph: 253-403-2394
Wisconsin
	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
	Stevens Point
	Marshfield Clinic at Saint Michael's Hospital
		Ali W. Bseiso	Ph: 715-389-4457
	Weston
	Diagnostic and Treatment 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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