S1001 PET-Directed Therapy in Treating Patients With Limited-Stage Diffuse Large B-Cell Lymphoma

A Phase II Trial of PET-Directed Therapy for Limited Stage Diffuse Large B-Cell Lymphoma (DLBCL)

RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone, work in different ways to stop cancer cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill cancer cells. 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. Radiolabeled monoclonal antibodies, such as yttrium Y 90 ibritumomab tiuxetan, can find cancer cells and carry cancer-killing substances to them without harming normal cells. Comparing results of diagnostic procedures, such as PET scan and CT scan, done before, during, and after chemotherapy may help doctors predict a patient's response to treatment and help plan the best treatment.

PURPOSE: This phase II trial studies how well PET-directed chemotherapy works in treating patients with limited-stage diffuse large B-cell lymphoma.

Study Overview

• Status: Completed
• Conditions: Lymphoma
• Intervention / Treatment: Drug: cyclophosphamide; Other: laboratory biomarker analysis; Drug: prednisone; Drug: vincristine sulfate; Drug: doxorubicin hydrochloride; Biological: rituximab; Radiation: fludeoxyglucose F 18; Radiation: yttrium Y 90 ibritumomab tiuxetan; Radiation: selective external radiation therapy; Other: R-CHOP regimen

Detailed Description

OBJECTIVES:

Primary

• To assess the 5-year progression-free survival (PFS) rate in patients with newly diagnosed limited-stage diffuse, large B-cell lymphoma (DLBCL) using positron emission tomography (PET)/CT scan to direct therapy after 3 courses of rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone (R-CHOP).

Secondary

• To evaluate PFS within the PET-positive (+) and PET-negative (-) subgroups of patients with newly diagnosed limited-stage DLBCL.
• To evaluate toxicity of the protocol treatments in this patient population.
• To evaluate the response probability in this patient population.
• To evaluate overall survival in the overall population, and within the PET+ and PET- subgroups.
• To estimate the rate of upstaging at baseline by PET/CT at baseline among patients newly diagnosed with limited-stage DLBCL by CT imaging and to describe outcomes in patients upstaged by PET/CT at baseline to advanced DLBCL.
• To describe outcomes in the subgroup of patients upstaged by PET/CT.
• To evaluate the association of germinal center B-cell subtype (GCB) vs stromal-1 vs stromal-2 gene expression signatures with PFS or overall survival.

OUTLINE: This is a multicenter study. Patients are stratified according to whether the patient was upstaged to advanced stage DLBCL, based on local review of the baseline PET/CT (yes vs no).

Chemotherapy: Patients receive R-CHOP comprising rituximab IV, cyclophosphamide IV over 30-60 minutes, vincristine sulfate IV, and doxorubicin hydrochloride IV on day 1, and prednisone orally on days 1-5. Treatment repeats every 21 days for 3* courses. NOTE: *Patients found to have advanced stage DLBCL based on local review of the baseline PET scan receive 6 courses of R-CHOP.

FDG/PET - Radiotherapy: Patients undergo fludeoxyglucose F 18 positron emission tomography (FDG-PET)/CT scan at baseline, on days 15-18 of course 3, and at 12 weeks after completion of course 3. Patients with complete response (PET scan negative) receive one additional course of R-CHOP as above. Patients with partial response (PET scan positive) undergo involved-field radiotherapy (IFRT) 5 days a week for approximately 4-5 weeks.

Monoclonal antibody: Beginning 3-6 weeks after completion of IFRT, patients receive yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes and rituximab IV on day 1 and on day 7, 8, or 9.

Patients may undergo blood sample collection at baseline for correlative studies. Bone marrow tissue samples may be also collected for correlative studies.

After completion of study therapy, patients are followed up every 6 months for 2 years and then yearly for 5 years.

• Study Type: Interventional
• Enrollment (Actual): 159
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alaska
    • Anchorage, Alaska, United States, 99508
      • Providence Cancer Center
  • Arizona
    • Tucson, Arizona, United States, 85724-5024
      • Arizona Cancer Center at University of Arizona Health Sciences Center
  • Colorado
    • Aurora, Colorado, United States, 80012
      • Aurora Presbyterian Hospital
    • Boulder, Colorado, United States, 80301-9019
      • Boulder Community Hospital
    • Colorado Springs, Colorado, United States, 80933
      • Penrose Cancer Center at Penrose Hospital
    • Denver, Colorado, United States, 80210
      • Porter Adventist Hospital
    • Denver, Colorado, United States, 80220
      • Rose Medical Center
    • Denver, Colorado, United States, 80218
      • Presbyterian - St. Luke's Medical Center
    • Denver, Colorado, United States, 80204
      • St. Anthony Central Hospital
    • Denver, Colorado, United States, 80218
      • St. Joseph Hospital
    • Denver, Colorado, United States, 80222
      • CCOP - Colorado Cancer Research Program
    • Denver, Colorado, United States, 80205
      • Kaiser Permanente - Denver
    • Englewood, Colorado, United States, 80110
      • Swedish Medical Center
    • Grand Junction, Colorado, United States, 81502
      • St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center
    • Greeley, Colorado, United States, 80631
      • North Colorado Medical Center
    • Lafayette, Colorado, United States, 80026
      • Kaiser Permanente - Lafayette
    • Littleton, Colorado, United States, 80122
      • Littleton Adventist Hospital
    • Lone Tree, Colorado, United States, 80124
      • Sky Ridge Medical Center
    • Longmont, Colorado, United States, 80501
      • Hope Cancer Care Center at Longmont United Hospital
    • Loveland, Colorado, United States, 80539
      • McKee Medical Center
    • Parker, Colorado, United States, 80138
      • Parker Adventist Hospital
    • Pueblo, Colorado, United States, 81004
      • St. Mary - Corwin Regional Medical Center
    • Thornton, Colorado, United States, 80229
      • North Suburban Medical Center
    • Wheat Ridge, Colorado, United States, 80033
      • Exempla Lutheran Medical Center
  • Connecticut
    • Hartford, Connecticut, United States, 06105
      • Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center
    • New Haven, Connecticut, United States, 06520-8028
      • Yale Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Piedmont Hospital
    • Atlanta, Georgia, United States, 30342-1611
      • Northside Hospital Cancer Center
    • Atlanta, Georgia, United States, 30342-1701
      • Saint Joseph's Hospital of Atlanta
    • Atlanta, Georgia, United States, 30342
      • CCOP - Atlanta Regional
    • Austell, Georgia, United States, 30106
      • WellStar Cobb Hospital
    • Columbus, Georgia, United States, 31904
      • John B. Amos Cancer Center
    • Decatur, Georgia, United States, 30033
      • Charles B. Eberhart Cancer Center at DeKalb Medical Center
    • Fayetteville, Georgia, United States, 30214
      • Piedmont Fayette Hospital
    • Lawrenceville, Georgia, United States, 30045
      • Gwinnett Medical Center
    • Marietta, Georgia, United States, 30060
      • Kennestone Cancer Center at Wellstar Kennestone Hospital
    • Riverdale, Georgia, United States, 30274-2600
      • Southern Regional Medical Center
    • Rome, Georgia, United States, 30165
      • Harbin Clinic Cancer Center - Medical Oncology
  • Hawaii
    • 'Aiea, Hawaii, United States, 96701
      • Kapiolani Medical Center at Pali Momi
    • 'Aiea, Hawaii, United States, 96701
      • Oncare Hawaii, Incorporated - Pali Momi
    • 'Ewa Beach, Hawaii, United States, 96706
      • Leeward Radiation Oncology
    • Honolulu, Hawaii, United States, 96813
      • Cancer Research Center of Hawaii
    • Honolulu, Hawaii, United States, 96817
      • Kuakini Medical Center
    • Honolulu, Hawaii, United States, 96826
      • Kapiolani Medical Center for Women and Children
    • Honolulu, Hawaii, United States, 96813
      • OnCare Hawaii, Incorporated - Lusitana
    • Honolulu, Hawaii, United States, 96813
      • Queen's Cancer Institute at Queen's Medical Center
    • Honolulu, Hawaii, United States, 96813
      • Straub Clinic and Hospital, Incorporated
    • Honolulu, Hawaii, United States, 96817
      • Hawaii Medical Center - East
    • Honolulu, Hawaii, United States, 96817-3169
      • OnCare Hawaii, Incorporated - Kuakini
    • Kailua, Hawaii, United States, 96734
      • Castle Medical Center
    • Lihue, Hawaii, United States, 96766
      • Kauai Medical Clinic
  • Idaho
    • Boise, Idaho, United States, 83712
      • Mountain States Tumor Institute at St. Luke's Regional Medical Center
    • Boise, Idaho, United States, 83706
      • Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center
  • Illinois
    • Bloomington, Illinois, United States, 61701
      • Illinois CancerCare - Bloomington
    • Bloomington, Illinois, United States, 61701
      • St. Joseph Medical Center
    • Canton, Illinois, United States, 61520
      • Illinois CancerCare - Canton
    • Canton, Illinois, United States, 61520
      • Graham Hospital
    • Carthage, Illinois, United States, 62321
      • Memorial Hospital
    • Carthage, Illinois, United States, 62321
      • Illinois CancerCare - Carthage
    • Chicago, Illinois, United States, 60611-3013
      • Robert H. Lurie Comprehensive Cancer Center at Northwestern University
    • Chicago, Illinois, United States, 60611
      • Hematology and Oncology Associates
    • Eureka, Illinois, United States, 61530
      • Illinois CancerCare - Eureka
    • Eureka, Illinois, United States, 61530
      • Eureka Community Hospital
    • Galesburg, Illinois, United States, 61401
      • Illinois CancerCare - Galesburg
    • Galesburg, Illinois, United States, 61401
      • Galesburg Clinic, PC
    • Havana, Illinois, United States, 62644
      • Illinois CancerCare - Havana
    • Highland Park, Illinois, United States, 60035
      • Kellogg Cancer Care Center
    • Kankakee, Illinois, United States, 60901
      • Provena St. Mary's Regional Cancer Center - Kankakee
    • Kewanee, Illinois, United States, 61443
      • Illinois CancerCare - Kewanee Clinic
    • Libertyville, Illinois, United States, 60048
      • North Shore Oncology and Hematology Associates, Limited - Libertyville
    • Macomb, Illinois, United States, 61455
      • Illinois CancerCare - Macomb
    • Macomb, Illinois, United States, 61455
      • McDonough District Hospital
    • Monmouth, Illinois, United States, 61462
      • Illinois CancerCare - Monmouth
    • Monmouth, Illinois, United States, 61462
      • OSF Holy Family Medical Center
    • Niles, Illinois, United States, 60714
      • Cancer Care and Hematology Specialists of Chicagoland - Niles
    • Normal, Illinois, United States, 61761
      • BroMenn Regional Medical Center
    • Normal, Illinois, United States, 61761
      • Community Cancer Center
    • Normal, Illinois, United States, 61761
      • Illinois CancerCare - Community Cancer Center
    • Ottawa, Illinois, United States, 61350
      • Community Hospital of Ottawa
    • Ottawa, Illinois, United States, 61350
      • Oncology Hematology Associates of Central Illinois, PC - Ottawa
    • Pekin, Illinois, United States, 61554
      • Cancer Treatment Center at Pekin Hospital
    • Pekin, Illinois, United States, 61603
      • Illinois CancerCare - Pekin
    • Peoria, Illinois, United States, 61636
      • Methodist Medical Center of Illinois
    • Peoria, Illinois, United States, 61614
      • Proctor Hospital
    • Peoria, Illinois, United States, 61637
      • OSF St. Francis Medical Center
    • Peoria, Illinois, United States, 61615
      • CCOP - Illinois Oncology Research Association
    • Peoria, Illinois, United States, 61615
      • Oncology Hematology Associates of Central Illinois, PC - Peoria
    • Peru, Illinois, United States, 61354
      • Illinois CancerCare - Peru
    • Peru, Illinois, United States, 61354
      • Illinois Valley Community Hospital
    • Princeton, Illinois, United States, 61356
      • Perry Memorial Hospital
    • Princeton, Illinois, United States, 61356
      • Illinois CancerCare - Princeton
    • Skokie, Illinois, United States, 60076
      • Hematology Oncology Associates - Skokie
    • Spring Valley, Illinois, United States, 61362
      • Illinois CancerCare - Spring Valley
  • Indiana
    • Beech Grove, Indiana, United States, 46107
      • St. Francis Hospital and Health Centers - Beech Grove Campus
    • Richmond, Indiana, United States, 47374
      • Reid Hospital & Health Care Services
  • Iowa
    • Sioux City, Iowa, United States, 51101
      • Siouxland Hematology-Oncology Associates, LLP
    • Sioux City, Iowa, United States, 51102
      • Mercy Medical Center - Sioux City
    • Sioux City, Iowa, United States, 51104
      • St. Luke's Regional Medical Center
  • Kansas
    • Chanute, Kansas, United States, 66720
      • Cancer Center of Kansas, PA - Chanute
    • Dodge City, Kansas, United States, 67801
      • Cancer Center of Kansas, PA - Dodge City
    • El Dorado, Kansas, United States, 67042
      • Cancer Center of Kansas, PA - El Dorado
    • Fort Scott, Kansas, United States, 66701
      • Cancer Center of Kansas - Fort Scott
    • Independence, Kansas, United States, 67301
      • Cancer Center of Kansas-Independence
    • Kingman, Kansas, United States, 67068
      • Cancer Center of Kansas, PA - Kingman
    • Lawrence, Kansas, United States, 66044
      • Lawrence Memorial Hospital
    • Liberal, Kansas, United States, 67901
      • Cancer Center of Kansas, PA - Liberal
    • McPherson, Kansas, United States, 67460
      • Cancer Center of Kansas, PA - McPherson
    • Newton, Kansas, United States, 67114
      • Cancer Center of Kansas, PA - Newton
    • Overland Park, Kansas, United States, 66209
      • Menorah Medical Center
    • Overland Park, Kansas, United States, 66213
      • Saint Luke's Hospital - South
    • Parsons, Kansas, United States, 67357
      • Cancer Center of Kansas, PA - Parsons
    • Prairie Village, Kansas, United States, 66208
      • CCOP - Kansas City
    • Pratt, Kansas, United States, 67124
      • Cancer Center of Kansas, PA - Pratt
    • Salina, Kansas, United States, 67401
      • Cancer Center of Kansas, PA - Salina
    • Wellington, Kansas, United States, 67152
      • Cancer Center of Kansas, PA - Wellington
    • Wichita, Kansas, United States, 67208
      • Cancer Center of Kansas, PA - Medical Arts Tower
    • Wichita, Kansas, United States, 67214
      • Cancer Center of Kansas, PA - Wichita
    • Wichita, Kansas, United States, 67214
      • CCOP - Wichita
    • Wichita, Kansas, United States, 67214
      • Via Christi Cancer Center at Via Christi Regional Medical Center
    • Wichita, Kansas, United States, 67208
      • Associates in Womens Health, PA - North Review
    • Winfield, Kansas, United States, 67156
      • Cancer Center of Kansas, PA - Winfield
  • Kentucky
    • Lexington, Kentucky, United States, 40536-0093
      • Lucille P. Markey Cancer Center at University of Kentucky
  • Michigan
    • Ann Arbor, Michigan, United States, 48106-0995
      • Saint Joseph Mercy Cancer Center
    • Ann Arbor, Michigan, United States, 48106
      • CCOP - Michigan Cancer Research Consortium
    • Dearborn, Michigan, United States, 48123-2500
      • Oakwood Cancer Center at Oakwood Hospital and Medical Center
    • Detroit, Michigan, United States, 48202
      • Josephine Ford Cancer Center at Henry Ford Hospital
    • Flint, Michigan, United States, 48503
      • Hurley Medical Center
    • Flint, Michigan, United States, 48503
      • Genesys Hurley Cancer Institute
    • Grand Blanc, Michigan, United States, 48439
      • Genesys Regional Medical Center
    • Grosse Pointe Woods, Michigan, United States, 48236
      • Van Elslander Cancer Center at St. John Hospital and Medical Center
    • Jackson, Michigan, United States, 49201
      • Foote Memorial Hospital
    • Kalamazoo, Michigan, United States, 49007
      • Bronson Methodist Hospital
    • Kalamazoo, Michigan, United States, 49001
      • Borgess Medical Center
    • Kalamazoo, Michigan, United States, 49007-3731
      • West Michigan Cancer Center
    • Lansing, Michigan, United States, 48912-1811
      • Sparrow Regional Cancer Center
    • Livonia, Michigan, United States, 48154
      • St. Mary Mercy Hospital
    • Pontiac, Michigan, United States, 48341-2985
      • St. Joseph Mercy Oakland
    • Port Huron, Michigan, United States, 48060
      • Mercy Regional Cancer Center at Mercy Hospital
    • Saginaw, Michigan, United States, 48601
      • Seton Cancer Institute at Saint Mary's - Saginaw
    • Warren, Michigan, United States, 48093
      • St. John Macomb Hospital
  • Minnesota
    • Burnsville, Minnesota, United States, 55337
      • Fairview Ridges Hospital
    • Coon Rapids, Minnesota, United States, 55433
      • Mercy and Unity Cancer Center at Mercy Hospital
    • Duluth, Minnesota, United States, 55805
      • CCOP - Duluth
    • Duluth, Minnesota, United States, 55805-1983
      • Duluth Clinic Cancer Center - Duluth
    • Duluth, Minnesota, United States, 55805
      • Miller - Dwan Medical Center
    • Edina, Minnesota, United States, 55435
      • Fairview Southdale Hospital
    • Fridley, Minnesota, United States, 55432
      • Mercy and Unity Cancer Center at Unity Hospital
    • Hutchinson, Minnesota, United States, 55350
      • Hutchinson Area Health Care
    • Maplewood, Minnesota, United States, 55109
      • HealthEast Cancer Care at St. John's Hospital
    • Maplewood, Minnesota, United States, 55109
      • Minnesota Oncology - Maplewood
    • Minneapolis, Minnesota, United States, 55407
      • Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center - Minneapolis
    • New Ulm, Minnesota, United States, 56073
      • New Ulm Medical Center
    • Robbinsdale, Minnesota, United States, 55422-2900
      • Humphrey Cancer Center at North Memorial Outpatient Center
    • Saint Louis Park, Minnesota, United States, 55416
      • CCOP - Metro-Minnesota
    • Saint Louis Park, Minnesota, United States, 55416
      • Park Nicollet Cancer Center
    • Saint Paul, Minnesota, United States, 55102
      • United Hospital
    • Saint Paul, Minnesota, United States, 55101
      • Regions Hospital Cancer Care Center
    • Shakopee, Minnesota, United States, 55379
      • St. Francis Cancer Center at St. Francis Medical Center
    • Stillwater, Minnesota, United States, 55082
      • Lakeview Hospital
    • Waconia, Minnesota, United States, 55387
      • Ridgeview Medical Center
    • Willmar, Minnesota, United States, 56201
      • Willmar Cancer Center at Rice Memorial Hospital
    • Woodbury, Minnesota, United States, 55125
      • Minnesota Oncology - Woodbury
  • Missouri
    • Kansas City, Missouri, United States, 64116
      • North Kansas City Hospital
    • Kansas City, Missouri, United States, 64132
      • Research Medical Center
    • Kansas City, Missouri, United States, 64111
      • Saint Luke's Cancer Institute at Saint Luke's Hospital
    • Kansas City, Missouri, United States, 64118
      • Heartland Hematology Oncology Associates, Incorporated
    • Lee's Summit, Missouri, United States, 64086
      • Saint Luke's East - Lee's Summit
    • Liberty, Missouri, United States, 64068
      • Parvin Radiation Oncology
    • Saint Joseph, Missouri, United States, 64506
      • Heartland Regional Medical Center
    • Saint Joseph, Missouri, United States, 64507
      • Saint Joseph Oncology, Incorporated
    • Saint Louis, Missouri, United States, 63110
      • Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
  • Montana
    • Billings, Montana, United States, 59101
      • CCOP - Montana Cancer Consortium
    • Billings, Montana, United States, 59101
      • St. Vincent Healthcare Cancer Care Services
    • Billings, Montana, United States, 59107-7000
      • Billings Clinic - Downtown
    • Billings, Montana, United States, 59102
      • Hematology-Oncology Centers of the Northern Rockies - Billings
    • Bozeman, Montana, United States, 59715
      • Bozeman Deaconess Cancer Center
    • Butte, Montana, United States, 59701
      • St. James Healthcare Cancer Care
    • Great Falls, Montana, United States, 59405
      • Great Falls Clinic - Main Facility
    • Great Falls, Montana, United States, 59405
      • Sletten Cancer Institute at Benefis Healthcare
    • Helena, Montana, United States, 59601
      • St. Peter's Hospital
    • Kalispell, Montana, United States, 59901
      • Kalispell Regional Medical Center
    • Kalispell, Montana, United States, 59901
      • Glacier Oncology, PLLC
    • Kalispell, Montana, United States, 59901
      • Kalispell Medical Oncology at KRMC
    • Missoula, Montana, United States, 59807-7877
      • Montana Cancer Specialists at Montana Cancer Center
    • Missoula, Montana, United States, 59807
      • Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
  • New York
    • Rochester, New York, United States, 14642
      • James P. Wilmot Cancer Center at University of Rochester Medical Center
  • North Carolina
    • Goldsboro, North Carolina, United States, 27534
      • Wayne Memorial Hospital, Incorporated
    • Raleigh, North Carolina, United States, 27607
      • Rex Cancer Center at Rex Hospital
    • Statesville, North Carolina, United States, 28677
      • Iredell Memorial Hospital
  • North Dakota
    • Fargo, North Dakota, United States, 58122
      • CCOP - MeritCare Hospital
    • Fargo, North Dakota, United States, 58102
      • MeritCare Broadway
    • Fargo, North Dakota, United States, 58122
      • Roger Maris Cancer Center at MeritCare Hospital
  • Ohio
    • Dayton, Ohio, United States, 45405
      • Grandview Hospital
    • Dayton, Ohio, United States, 45406
      • Good Samaritan Hospital
    • Dayton, Ohio, United States, 45409
      • David L. Rike Cancer Center at Miami Valley Hospital
    • Dayton, Ohio, United States, 45415
      • Samaritan North Cancer Care Center
    • Dayton, Ohio, United States, 45420
      • CCOP - Dayton
    • Findlay, Ohio, United States, 45840
      • Blanchard Valley Medical Associates
    • Franklin, Ohio, United States, 45005-1066
      • Middletown Regional Hospital
    • Greenville, Ohio, United States, 45331
      • Wayne Hospital
    • Kettering, Ohio, United States, 45429
      • Charles F. Kettering Memorial Hospital
    • Troy, Ohio, United States, 45373-1300
      • UVMC Cancer Care Center at Upper Valley Medical Center
    • Xenia, Ohio, United States, 45385
      • Ruth G. McMillan Cancer Center at Greene Memorial Hospital
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74136
      • Natalie Warren Bryant Cancer Center at St. Francis Hospital
  • Pennsylvania
    • Danville, Pennsylvania, United States, 17822-0001
      • Geisinger Cancer Institute at Geisinger Health
  • South Carolina
    • Greenville, South Carolina, United States, 29615
      • CCOP - Greenville
    • Greenville, South Carolina, United States, 29605
      • Greenville Hospital Cancer Center
    • Greenville, South Carolina, United States, 29605
      • Cancer Centers of the Carolinas - Faris Road
    • Greenville, South Carolina, United States, 29605
      • Cancer Centers of the Carolinas - Grove Commons
    • Greer, South Carolina, United States, 29650
      • Cancer Centers of the Carolinas - Greer Medical Oncology
    • Seneca, South Carolina, United States, 29672
      • Cancer Centers of the Carolinas - Seneca
    • Spartanburg, South Carolina, United States, 29303
      • CCOP - Upstate Carolina
    • Spartanburg, South Carolina, United States, 29303
      • Gibbs Regional Cancer Center at Spartanburg Regional Medical Center
    • Spartanburg, South Carolina, United States, 29307
      • Cancer Centers of the Carolinas - Spartanburg
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57117-5039
      • Sanford Cancer Center at Sanford USD Medical Center
  • Texas
    • San Antonio, Texas, United States, 78229
      • Cancer Therapy and Research Center
    • San Antonio, Texas, United States, 78229-3900
      • University of Texas Health Science Center at San Antonio
    • San Antonio, Texas, United States, 78229
      • University Hospital - San Antonio
  • Washington
    • Anacortes, Washington, United States, 98221
      • Island Hospital Cancer Care Center at Island Hospital
    • Bellingham, Washington, United States, 98225
      • St. Joseph Cancer Center
    • Bremerton, Washington, United States, 98310
      • Olympic Hematology and Oncology
    • Burien, Washington, United States, 98166
      • Highline Medical Center Cancer Center
    • Kennewick, Washington, United States, 99336
      • Columbia Basin Hematology
    • Mount Vernon, Washington, United States, 98274
      • Skagit Valley Hospital Cancer Care Center
    • Poulsbo, Washington, United States, 98370
      • Harrison Poulsbo Hematology and Onocology
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center
    • Seattle, Washington, United States, 98104
      • Harborview Medical Center
    • Seattle, Washington, United States, 98104
      • Minor and James Medical, PLLC
    • Seattle, Washington, United States, 98112
      • Group Health Central Hospital
    • Seattle, Washington, United States, 98122-4307
      • Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
    • Seattle, Washington, United States, 98122
      • Polyclinic First Hill
    • Seattle, Washington, United States, 98195
      • University Cancer Center at University of Washington Medical Center
    • Sedro-Woolley, Washington, United States, 98284
      • North Puget Oncology at United General Hospital
    • Spokane, Washington, United States, 99202
      • Cancer Care Northwest - Spokane South
    • Spokane, Washington, United States, 99218
      • Evergreen Hematology and Oncology, PS
    • Wenatchee, Washington, United States, 98801-2028
      • Wenatchee Valley Medical Center
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • Mary Babb Randolph Cancer Center at West Virginia University Hospitals
  • Wisconsin
    • La Crosse, Wisconsin, United States, 54601
      • Gundersen Lutheran Center for Cancer and Blood
  • Wyoming
    • Casper, Wyoming, United States, 82609
      • Rocky Mountain Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

DISEASE CHARACTERISTICS:

• Patients must have biopsy-proven diffuse large B-cell lymphoma (DLBCL)

  • Adequate sections or a paraffin block from the original diagnostic specimen must be submitted for review by the lymphoma pathology group
  • Lymphoma must express CD20 antigen by either flow cytometry using anti-CD20 antibodies or by immunoperoxidase staining of paraffin sections
  • Patients with primary mediastinal lymphoma or testicular lymphoma are not eligible

• Patients must have non-bulky stage I or II disease by Ann Arbor classification

  • This staging excludes FDG-PET evaluation
  • Patients who have stage I or II non-bulky disease on diagnostic CT scan, but are upstaged to stage III or IV based on FDG-PET evaluation, are also eligible

• Patients must have a diagnostic quality contrast-enhanced CT scan of the chest, abdomen, and pelvis AND baseline FDG-PET scan performed within 28 days prior to registration

  • Low-resolution "localization" CT scans performed as part of a combined PET/CT scan are not adequate for enrollment or response determination on this protocol
  • If a patient has an allergy to CT contrast, then a non-enhanced CT will be acceptable

• Patients must not have clinical evidence of central nervous system (CNS) involvement by lymphoma

  • Any laboratory or radiographic tests performed to assess CNS involvement must be negative and must be performed within 42 days prior to registration

• Patients may have either measurable or evaluable limited-stage DLBCL

  • Patients rendered free of measurable or evaluable disease by virtue of biopsy (resection) are also eligible
  • If patient has measurable disease it must be documented on the Lymphoma Baseline Tumor Assessment Form (Form #15187)
  • All measurable disease must be assessed within 28 days prior to registration
  • Patients with non-measurable disease in addition to measurable disease must have all non-measurable disease assessed within 42 days prior to registration
• Patients must have a unilateral or bilateral bone marrow biopsy performed within 42 days prior to registration

PATIENT CHARACTERISTICS:

• Zubrod performance status 0-2
• Absolute neutrophil count (ANC) ≥ 1,000/mm³
• Platelet count ≥ 100,000/mm³
• Total bilirubin ≤ 2 times upper limit of normal (ULN) (unless due to Gilbert syndrome)
• Patients must not be pregnant or nursing
• Women/men of reproductive potential must have agreed to use an effective contraceptive method during the study period
• Patients must not be known to be HIV-positive

• No other prior malignancy is allowed except for the following:

  • Adequately treated basal cell or squamous cell skin cancer
  • In situ cervical cancer
  • Adequately treated stage I or II cancer from which the patient is currently in complete remission
  • Any other cancer from which the patient has been disease-free for 5 years

PRIOR CONCURRENT THERAPY:

• Patients must not have received prior chemotherapy, radiotherapy, or antibody therapy for lymphoma

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: PET Negative: R-CHOP; R-CHOP x 3 Cycles	Drug: cyclophosphamide; Other: laboratory biomarker analysis; Drug: prednisone; Drug: vincristine sulfate; Drug: doxorubicin hydrochloride; Biological: rituximab; Other: R-CHOP regimen
Experimental: PET Positive: IFRT +Zevalin; Standard IFRT+ Zevalin IV per ABW	Other: laboratory biomarker analysis; Biological: rituximab; Radiation: fludeoxyglucose F 18; Radiation: yttrium Y 90 ibritumomab tiuxetan; Radiation: selective external radiation therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Five-year Progression-free Survival (PFS) Rate in Patients With Newly Diagnosed Limited Stage Diffuse Large B-cell Lymphoma (DLBCL)	Measured from date of registration to date of first observation of progressive disease, or death due to any cause. Patients last known to be alive without report of progression or relapse are censored at date of last contact. Progressions is defined using the 2007 revised Cheson et. Al. criteria, as ≥50% increase in the sum of the products of diameters (SPD) of target measurable lesions, appearance of any new bone marrow involvement, or appearance of any new lesion >1.5 cm in the longest axis.	up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS) Within the PET+ and PET- Subgroups of Patients With Newly Diagnosed Limited-stage Diffuse Large B-Cell Lymphoma (DLBCL)	Measured from date of interim positron emission tomography (PET)/computed tomography scan to date of first observation of progressive disease, or death due to any cause. Patients last known to be alive without report of progression or relapse are censored at date of last contact.	up to 5 years
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug	Adverse Events (AEs) are reported by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal.	up to 4 months or time of disease progression.
Overall Survival of Patients With Newly Diagnosed Limited-stage Diffuse Large B-Cell Lymphoma (DLBCL)	Measured from date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact.	up to 5 years
Response Rates in Patients With Newly Diagnosed Limited Stage Diffuse Large B-cell Lymphoma Using PET/CT Scan to Direct Therapy After 3 Cycles of R-CHOP	Complete Response (CR) is a complete disappearance of all disease with the exception of the following. If no PET scan or when the PET scan was positive before therapy, a post-treatment residual mass of any size is permitted if it is PET negative. If the PET scan was negative before therapy, all nodal masses at baseline must have regressed. No new lesions. Previously enlarged organs must have regressed and not be palpable. Bone marrow (BM) must be negative if positive at baseline. Normalization of markers. Partial Response (PR) is a 50% decrease in the sum of products of greatest diameters (SPD) for up to 6 identified dominant lesions, including spleenic and hepatic nodules from baseline. No new lesions and no increase in the size of liver, spleen or other nodes. If PET scan or when the PET scan was positive before therapy, PET should be positive in at least one previously involved site.	Up to 4 months
Association of Germinal Center B-cell Subtype (GCB) vs Stromal-1 vs Stromal-2 Gene Expression Signatures With PFS or Overall Survival	Formalin-fixed, paraffin-embedded tissue from the diagnostic biopsy is collected and used to determine germinal center B-cell (GCB) phenotype. GCB subtype of DLBCL is defined by gene-expression profiling that is performed using quantitative nuclease protection assay (qNPA).	5 years

Collaborators and Investigators

• Sponsor: SWOG Cancer Research Network
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Daniel O. Persky, MD, Yale University

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): June 3, 2020
• Study Completion (Actual): December 1, 2023

Study Registration Dates

• First Submitted: May 21, 2011
• First Submitted That Met QC Criteria: May 24, 2011
• First Posted (Estimated): May 25, 2011

Study Record Updates

• Last Update Posted (Actual): February 8, 2024
• Last Update Submitted That Met QC Criteria: February 6, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: stage III adult diffuse large cell lymphoma; stage IV adult diffuse large cell lymphoma; noncontiguous stage II adult diffuse large cell lymphoma; contiguous stage II adult diffuse large cell lymphoma; stage I adult diffuse large cell lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Radiopharmaceuticals; Antibiotics, Antineoplastic; Cyclophosphamide; Fluorodeoxyglucose F18; Rituximab; Prednisone; Doxorubicin; Liposomal doxorubicin; Vincristine
• Other Study ID Numbers: CDR0000700624; U10CA032102 (U.S. NIH Grant/Contract); S1001 (Other Identifier: SWOG)