Phase III Randomized Study of R-CHOP V. Dose-Adjusted EPOCH-R With Molecular Profiling in Untreated De Novo Diffuse Large B-Cell Lymphomas
- 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.
- 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
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
- 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.
Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment
Event-free survival 5 years after completion of study treatment
Wyndham H. Wilson, MD, PhD
National Cancer Institute (NCI)
|National Naval Medical Center||Bethesda, Maryland 20889|
|Cardinal Bernardin Cancer Center at Loyola University Medical Center||Maywood, Illinois 60153-5500|
|CCOP - Christiana Care Health Services||Wilmington, Delaware 19899|
|Mercy Cancer Center at Mercy Medical Center||Canton, Ohio 44708|
|Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center||Wilkes-Barre, Pennsylvania 18711|
|Marshfield Clinic - Marshfield Center||Marshfield, Wisconsin 54449|
|Marshfield Clinic - Indianhead Center||Rice Lake, Wisconsin 54868|
|Naval Medical Center - San Diego||San Diego, California 92134-3202|
|Rebecca and John Moores UCSD Cancer Center||La Jolla, California 92093-0658|
|Alvin and Lois Lapidus Cancer Institute at Sinai Hospital||Baltimore, Maryland 21215|
|Presbyterian Cancer Center at Presbyterian Hospital||Charlotte, North Carolina 28233-3549|
|Wake Forest University Comprehensive Cancer Center||Winston-Salem, North Carolina 27157-1096|
|Mary Babb Randolph Cancer Center at West Virginia University Hospitals||Morgantown, West Virginia 26506|
|James P. Wilmot Cancer Center at University of Rochester Medical Center||Rochester, New York 14642|
|New York Weill Cornell Cancer Center at Cornell University||New York, New York 10021|
|University of Illinois Cancer Center||Chicago, Illinois 60612-7243|
|Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis||St. Louis, Missouri 63110|
|Geisinger Cancer Institute at Geisinger Health||Danville, Pennsylvania 17822-0001|
|Virginia Commonwealth University Massey Cancer Center||Richmond, Virginia 23298-0037|
|Madigan Army Medical Center - Tacoma||Tacoma, Washington 98431|
|Robert H. Lurie Comprehensive Cancer Center at Northwestern University||Chicago, Illinois 60611|
|Providence Cancer Institute at Providence Hospital - Southfield Campus||Southfield, Michigan 48075|
|Charles R. Wood Cancer Center at Glens Falls Hospital||Glens Falls, New York 12801|
|Iredell Memorial Hospital||Statesville, North Carolina 28677|
|Mountainview Medical||Berlin, Vermont 05602|
|NIH - Warren Grant Magnuson Clinical Center||Bethesda, Maryland 20892-1182|
|Palo Alto Medical Foundation||Palo Alto, California 94301|
|Creticos Cancer Center at Advocate Illinois Masonic Medical Center||Chicago, Illinois 60657|
|Altru Cancer Center at Altru Hospital||Grand Forks, North Dakota 58201|
|Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital||Pittsburgh, Pennsylvania 15224-1791|
|Eastern Connecticut Hematology and Oncology Associates||Norwich, Connecticut 06360|
|Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center||Columbus, Ohio 43210-1240|
|Geisinger Hazleton Cancer Center||Hazleton, Pennsylvania 18201|
|Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center||Hershey, Pennsylvania 17033-0850|
|Saint Joseph's Hospital||Marshfield, Wisconsin 54449|
|Marshfield Clinic - Lakeland Center||Minocqua, Wisconsin 54548|
|Ministry Medical Group at Saint Mary's Hospital||Rhinelander, Wisconsin 54501|
|Marshfield Clinic at Saint Michael's Hospital||Stevens Point, Wisconsin 54481|
|Saint Michael's Hospital Cancer Center||Stevens Point, Wisconsin 54481|
|Marshfield Clinic - Weston Center||Weston, Wisconsin 54476|
|Easton Regional Cancer Center at Easton Hospital||Easton, Pennsylvania 18042|
|Kinston Medical Specialists||Kinston, North Carolina 28501|
|New Hampshire Oncology - Hematology, PA at Payson Center for Cancer Care||Concord, New Hampshire 03301|
|New Hampshire Oncology - Hematology, PA - Hooksett||Hooksett, New Hampshire 03106|
|Camino Medical Group - Treatment Center||Mountain View, California 94040|
|Saint Helena Hospital||Saint Helena, California 94574|