Тестирование CC-486 (пероральный азацитидин) в сочетании со стандартной лекарственной терапией у пациентов в возрасте 75 лет и старше с недавно диагностированной диффузной крупноклеточной В-клеточной лимфомой
Рандомизированное исследование фазы II/III R-MiniCHOP с CC-486 или без него (пероральный азацитидин) у участников в возрасте 75 лет и старше с недавно диагностированной диффузной крупноклеточной В-клеточной лимфомой, фолликулярной лимфомой степени IIIB, трансформированной лимфомой и высокой степенью B -клеточные лимфомы с перестройками MYC, BCL2 и/или BCL6
This phase II/III trial compares the side effects and activity of oral azacitidine in combination with the standard drug therapy (reduced dose rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone [R-miniCHOP]) versus R-miniCHOP alone in treating patients 75 years or older with newly diagnosed diffuse large B cell lymphoma. R-miniCHOP includes a monoclonal antibody (a type of protein), called rituximab, which attaches to the lymphoma cells and may help the immune system kill these cells. R-miniCHOP also includes prednisone which is an anti-inflammatory medication and a combination of 3 chemotherapy drugs, cyclophosphamide, doxorubicin, and vincristine. These 3 chemotherapy drugs, as well as oral azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Combining oral azacitidine with R-miniCHOP may shrink the cancer or extend the time without disease symptoms coming back or extend patient's survival when compared to R-miniCHOP alone.
Обзор исследования
Статус
Условия
- Лимфоплазмоцитарная лимфома
- Анн-Арбор Стадия III Диффузная крупноклеточная В-клеточная лимфома
- Анн-Арбор Стадия IV Диффузная крупноклеточная В-клеточная лимфома
- В-клеточная лимфома высокой степени злокачественности с перестройками MYC и BCL2 или BCL6
- В-клеточная лимфома высокой степени злокачественности с перестройками MYC, BCL2 и BCL6
- Фолликулярная лимфома 3b степени
- Диффузная крупноклеточная В-клеточная лимфома, не уточненная иначе
- EBV-положительная диффузная крупноклеточная B-клеточная лимфома, не уточненная иначе
- В-клеточная лимфома высокой степени злокачественности, не уточненная иначе
- Диффузная крупноклеточная В-клеточная лимфома, связанная с хроническим воспалением
- Первичная кожная диффузная крупноклеточная В-клеточная лимфома, тип ноги
- Трансформированная фолликулярная лимфома в диффузную крупноклеточную В-клеточную лимфому
- Внутрисосудистая крупноклеточная В-клеточная лимфома
- Т-клеточная/богатая гистиоцитами крупная В-клеточная лимфома
- В-клеточная лимфома высокой степени злокачественности с перестройками MYC и BCL2 и/или BCL6
- Диффузная крупная В-клеточная лимфома Активированный В-клеточный тип
- Диффузная крупная В-клеточная лимфома Зародышевый центр В-клеточный тип
- HHV8-положительная диффузная крупноклеточная В-клеточная лимфома, не уточненная иначе
- Преобразование лимфомы маргинальной зоны в диффузную крупную В-клеточную лимфому
- Анн-Арбор Стадия IIX (объемная) диффузная крупноклеточная В-клеточная лимфома
- В-клеточная лимфома с преобладанием узловых лимфоцитов
Вмешательство/лечение
- Лекарство: Cyclophosphamide
- Лекарство: Doxorubicin Hydrochloride
- Лекарство: Prednisone
- Процедура: Biospecimen Collection
- Биологический: Rituximab
- Лекарство: Vincristine Sulfate
- Другой: Questionnaire Administration
- Процедура: Echocardiography Test
- Процедура: Multigated Acquisition Scan
- Процедура: Positron Emission Tomography
- Биологический: Rituximab and Hyaluronidase Human
- Процедура: Computed Tomography
- Лекарство: Oral Azacitidine
Подробное описание
PRIMARY OBJECTIVES:
I. To determine if the addition of CC-486 (oral azacitidine) to R-miniCHOP results in excess toxicity compared to R-miniCHOP alone that would preclude the combination from being studied further. (Safety run-in) II. To determine if the CC-486 + R-miniCHOP regimen should be tested further (Phase III) against the control R-miniCHOP alone based on progression-free survival (PFS). (Phase II component) III. To compare the overall survival (OS) between CC-486 + R-miniCHOP and R-miniCHOP alone. (Phase III component)
SECONDARY OBJECTIVES:
I. To assess the feasibility of delivering at least 4 cycles of CC-486 with R-miniCHOP in this population.
II. To assess toxicity for CC-486 + R-miniCHOP and for R-miniCHOP. III. To compare complete response rates, as defined by Lugano 2014 classification, between CC-486 + R-miniCHOP and R-miniCHOP alone.
INTEGRATED CORRELATIVE GERIATRIC ASSESSMENTS:
I. To compare functioning as assessed by the S1918 Comprehensive Geriatric Assessment (S1918 CGA) between participants treated with CC-486 + R-miniCHOP versus R-miniCHOP alone.
II. To evaluate if frailty status (fit/unfit versus [vs] frail/superfrail) as assessed by the FIL tool is associated with OS.
III. To evaluate if frailty as measured by the FIL tool correlates with the summary frailty index as measured using components of the S1918 CGA.
BANKING OBJECTIVE:
I. To bank specimens for future correlative studies.
OUTLINE:
Beginning 7 days prior to starting [protocol treatment, all patients receive vincristine sulfate intravenously (IV) on day 1, and prednisone orally (PO) daily on days 1-7.
Patients are then randomized to 1 of 2 arms.
ARM I: Patients receive CC-486 PO for 7 days prior to cycle 1. Patients then receive CC-486 PO on days 8-21. Treatment repeats every 21 days for cycles 1-5 in the absence of disease progression or unacceptable toxicity. Patients also receive rituximab IV (or rituximab and hyaluronidase human subcutaneously [SC] for cycles 2-6), cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 1, and prednisone PO on days 1-5. Treatment repeats every 21 days for cycles 1-6 (6 cycles total) in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) at screening and undergo positron emission tomography (PET)-computed tomography (CT) and blood sample collection throughout the study.
ARM II: Patients receive rituximab IV (or rituximab and hyaluronidase human SC for cycles 2-6), cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 1, and prednisone PO on days 1-5. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO or MUGA at screening and undergo PET-CT and blood sample collection throughout the study.
After completion of study treatment, patients are followed up periodically until 5 years from the date of registration.
Тип исследования
Регистрация (Оцененный)
Фаза
- Фаза 2
- Фаза 3
Контакты и местонахождение
Места учебы
-
-
Arizona
-
Tucson, Arizona, Соединенные Штаты, 85719
- Banner University Medical Center - Tucson
-
Tucson, Arizona, Соединенные Штаты, 85719
- University of Arizona Cancer Center-North Campus
-
-
Arkansas
-
Little Rock, Arkansas, Соединенные Штаты, 72205
- University of Arkansas for Medical Sciences
-
-
California
-
Anaheim, California, Соединенные Штаты, 92806
- Kaiser Permanente-Anaheim
-
Baldwin Park, California, Соединенные Штаты, 91706
- Kaiser Permanente-Baldwin Park
-
Bellflower, California, Соединенные Штаты, 90706
- Kaiser Permanente-Bellflower
-
Beverly Hills, California, Соединенные Штаты, 90211
- Tower Cancer Research Foundation
-
Costa Mesa, California, Соединенные Штаты, 92627
- UC Irvine Health Cancer Center-Newport
-
Duarte, California, Соединенные Штаты, 91010
- City of Hope Comprehensive Cancer Center
-
Fontana, California, Соединенные Штаты, 92335
- Kaiser Permanente-Fontana
-
Harbor City, California, Соединенные Штаты, 90710
- Kaiser Permanente South Bay
-
Huntington Beach, California, Соединенные Штаты, 92648
- City of Hope Seacliff
-
Irvine, California, Соединенные Штаты, 92618
- Kaiser Permanente-Irvine
-
Irvine, California, Соединенные Штаты, 92618
- City of Hope at Irvine Lennar
-
Lancaster, California, Соединенные Штаты, 93534
- City of Hope Antelope Valley
-
Long Beach, California, Соединенные Штаты, 90822
- Tibor Rubin VA Medical Center
-
Long Beach, California, Соединенные Штаты, 90813
- City of Hope at Long Beach Elm
-
Los Angeles, California, Соединенные Штаты, 90048
- Cedars-Sinai Medical Center
-
Los Angeles, California, Соединенные Штаты, 90027
- Kaiser Permanente Los Angeles Medical Center
-
Los Angeles, California, Соединенные Штаты, 90034
- Kaiser Permanente West Los Angeles
-
Newport Beach, California, Соединенные Штаты, 92660
- City of Hope Newport Beach
-
Ontario, California, Соединенные Штаты, 91761
- Kaiser Permanente-Ontario
-
Orange, California, Соединенные Штаты, 92868
- UC Irvine Health/Chao Family Comprehensive Cancer Center
-
Palo Alto, California, Соединенные Штаты, 94304
- Stanford Cancer Institute Palo Alto
-
Panorama City, California, Соединенные Штаты, 91402
- Kaiser Permanente - Panorama City
-
Riverside, California, Соединенные Штаты, 92505
- Kaiser Permanente-Riverside
-
San Diego, California, Соединенные Штаты, 92120
- Kaiser Permanente-San Diego Zion
-
San Marcos, California, Соединенные Штаты, 92078
- Kaiser Permanente-San Marcos
-
San Mateo, California, Соединенные Штаты, 94402
- UCSF Cancer Center - San Mateo
-
South Pasadena, California, Соединенные Штаты, 91030
- City of Hope South Pasadena
-
Torrance, California, Соединенные Штаты, 90503
- City of Hope South Bay
-
Upland, California, Соединенные Штаты, 91786
- City of Hope Upland
-
Woodland Hills, California, Соединенные Штаты, 91367
- Kaiser Permanente-Woodland Hills
-
-
Colorado
-
Golden, Colorado, Соединенные Штаты, 80401
- Lutheran Hospital - Cancer Centers of Colorado
-
-
Delaware
-
Newark, Delaware, Соединенные Штаты, 19713
- Helen F Graham Cancer Center
-
Newark, Delaware, Соединенные Штаты, 19713
- Delaware Clinical and Laboratory Physicians PA
-
Newark, Delaware, Соединенные Штаты, 19713
- Medical Oncology Hematology Consultants PA
-
-
Florida
-
Miami, Florida, Соединенные Штаты, 33136
- University of Miami Miller School of Medicine-Sylvester Cancer Center
-
-
Georgia
-
Atlanta, Georgia, Соединенные Штаты, 30308
- Emory University Hospital Midtown
-
Atlanta, Georgia, Соединенные Штаты, 30322
- Emory University Hospital/Winship Cancer Institute
-
Atlanta, Georgia, Соединенные Штаты, 30342
- Emory Saint Joseph's Hospital
-
Augusta, Georgia, Соединенные Штаты, 30912
- Augusta University Medical Center
-
-
Hawaii
-
Honolulu, Hawaii, Соединенные Штаты, 96813
- Queen's Medical Center
-
Honolulu, Hawaii, Соединенные Штаты, 96813
- Hawaii Cancer Care Inc - Waterfront Plaza
-
Honolulu, Hawaii, Соединенные Штаты, 96813
- Queen's Cancer Cenrer - POB I
-
Honolulu, Hawaii, Соединенные Штаты, 96813
- Straub Clinic and Hospital
-
Honolulu, Hawaii, Соединенные Штаты, 96817
- Queen's Cancer Center - Kuakini
-
‘Aiea, Hawaii, Соединенные Штаты, 96701
- Hawaii Cancer Care - Westridge
-
‘Aiea, Hawaii, Соединенные Штаты, 96701
- Pali Momi Medical Center
-
-
Illinois
-
Centralia, Illinois, Соединенные Штаты, 62801
- Centralia Oncology Clinic
-
Chicago, Illinois, Соединенные Штаты, 60611
- Northwestern University
-
Chicago, Illinois, Соединенные Штаты, 60637
- University of Chicago Comprehensive Cancer Center
-
Chicago, Illinois, Соединенные Штаты, 60612
- University of Illinois
-
Danville, Illinois, Соединенные Штаты, 61832
- Carle at The Riverfront
-
DeKalb, Illinois, Соединенные Штаты, 60115
- Northwestern Medicine Cancer Center Kishwaukee
-
Decatur, Illinois, Соединенные Штаты, 62526
- Decatur Memorial Hospital
-
Decatur, Illinois, Соединенные Штаты, 62526
- Cancer Care Specialists of Illinois - Decatur
-
Effingham, Illinois, Соединенные Штаты, 62401
- Crossroads Cancer Center
-
Effingham, Illinois, Соединенные Штаты, 62401
- Carle Physician Group-Effingham
-
Evanston, Illinois, Соединенные Штаты, 60201
- NorthShore University HealthSystem-Evanston Hospital
-
Geneva, Illinois, Соединенные Штаты, 60134
- Northwestern Medicine Cancer Center Delnor
-
Glenview, Illinois, Соединенные Штаты, 60026
- NorthShore University HealthSystem-Glenbrook Hospital
-
Glenview, Illinois, Соединенные Штаты, 60026
- Northwestern Medicine Glenview Outpatient Center
-
Grayslake, Illinois, Соединенные Штаты, 60030
- Northwestern Medicine Grayslake Outpatient Center
-
Highland Park, Illinois, Соединенные Штаты, 60035
- NorthShore University HealthSystem-Highland Park Hospital
-
Lake Forest, Illinois, Соединенные Штаты, 60045
- Northwestern Medicine Lake Forest Hospital
-
Mattoon, Illinois, Соединенные Штаты, 61938
- Carle Physician Group-Mattoon/Charleston
-
New Lenox, Illinois, Соединенные Штаты, 60451
- UC Comprehensive Cancer Center at Silver Cross
-
O'Fallon, Illinois, Соединенные Штаты, 62269
- Cancer Care Center of O'Fallon
-
Orland Park, Illinois, Соединенные Штаты, 60462
- University of Chicago Medicine-Orland Park
-
Orland Park, Illinois, Соединенные Штаты, 60462
- Northwestern Medicine Orland Park
-
Peoria, Illinois, Соединенные Штаты, 61615
- Illinois CancerCare-Peoria
-
Shiloh, Illinois, Соединенные Штаты, 62269
- Memorial Hospital East
-
Urbana, Illinois, Соединенные Штаты, 61801
- Carle Cancer Center
-
Warrenville, Illinois, Соединенные Штаты, 60555
- Northwestern Medicine Cancer Center Warrenville
-
-
Iowa
-
Ames, Iowa, Соединенные Штаты, 50010
- McFarland Clinic - Ames
-
Ankeny, Iowa, Соединенные Штаты, 50023
- UI Health Care Mission Cancer and Blood - Ankeny Clinic
-
Clive, Iowa, Соединенные Штаты, 50325
- UI Health Care Mission Cancer and Blood - West Des Moines Clinic
-
Des Moines, Iowa, Соединенные Штаты, 50309
- Iowa Methodist Medical Center
-
Des Moines, Iowa, Соединенные Штаты, 50309
- UI Health Care Mission Cancer and Blood - Des Moines Clinic
-
Des Moines, Iowa, Соединенные Штаты, 50314
- UI Health Care Mission Cancer and Blood - Laurel Clinic
-
-
Louisiana
-
Monroe, Louisiana, Соединенные Штаты, 71202
- Ochsner LSU Health Monroe Medical Center
-
Shreveport, Louisiana, Соединенные Штаты, 71103
- LSU Health Sciences Center at Shreveport
-
-
Massachusetts
-
Boston, Massachusetts, Соединенные Штаты, 02111
- Tufts Medical Center
-
-
Michigan
-
Ann Arbor, Michigan, Соединенные Штаты, 48106
- Trinity Health Saint Joseph Mercy Hospital Ann Arbor
-
Brighton, Michigan, Соединенные Штаты, 48114
- Trinity Health IHA Medical Group Hematology Oncology - Brighton
-
Brighton, Michigan, Соединенные Штаты, 48114
- Trinity Health Medical Center - Brighton
-
Canton, Michigan, Соединенные Штаты, 48188
- Trinity Health IHA Medical Group Hematology Oncology - Canton
-
Canton, Michigan, Соединенные Штаты, 48188
- Trinity Health Medical Center - Canton
-
Chelsea, Michigan, Соединенные Штаты, 48118
- Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
-
Chelsea, Michigan, Соединенные Штаты, 48118
- Chelsea Hospital
-
Livonia, Michigan, Соединенные Штаты, 48154
- Trinity Health Saint Mary Mercy Livonia Hospital
-
Livonia, Michigan, Соединенные Штаты, 48154
- Hope Cancer Clinic
-
Ypsilanti, Michigan, Соединенные Штаты, 48197
- Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
-
Ypsilanti, Michigan, Соединенные Штаты, 48106
- Huron Gastroenterology PC
-
-
Minnesota
-
Deer River, Minnesota, Соединенные Штаты, 56636
- Essentia Health - Deer River Clinic
-
Duluth, Minnesota, Соединенные Штаты, 55805
- Essentia Health Cancer Center
-
Hibbing, Minnesota, Соединенные Штаты, 55746
- Essentia Health Hibbing Clinic
-
Sandstone, Minnesota, Соединенные Штаты, 55072
- Essentia Health Sandstone
-
Virginia, Minnesota, Соединенные Штаты, 55792
- Essentia Health Virginia Clinic
-
-
Mississippi
-
Oxford, Mississippi, Соединенные Штаты, 38655
- Baptist Memorial Hospital and Cancer Center-Oxford
-
Southhaven, Mississippi, Соединенные Штаты, 38671
- Baptist Memorial Hospital and Cancer Center-Desoto
-
-
Missouri
-
Cape Girardeau, Missouri, Соединенные Штаты, 63703
- Saint Francis Medical Center
-
Chesterfield, Missouri, Соединенные Штаты, 63017
- Saint Luke's Hospital
-
City of Saint Peters, Missouri, Соединенные Штаты, 63376
- Siteman Cancer Center at Saint Peters Hospital
-
Creve Coeur, Missouri, Соединенные Штаты, 63141
- Siteman Cancer Center at West County Hospital
-
Saint Joseph, Missouri, Соединенные Штаты, 64506
- Heartland Regional Medical Center
-
St Louis, Missouri, Соединенные Штаты, 63110
- Washington University School of Medicine
-
St Louis, Missouri, Соединенные Штаты, 63129
- Siteman Cancer Center-South County
-
St Louis, Missouri, Соединенные Штаты, 63136
- Siteman Cancer Center at Christian Hospital
-
-
Nebraska
-
Lincoln, Nebraska, Соединенные Штаты, 68516
- Cancer Partners of Nebraska
-
-
New Jersey
-
Basking Ridge, New Jersey, Соединенные Штаты, 07920
- Memorial Sloan Kettering Basking Ridge
-
Englewood, New Jersey, Соединенные Штаты, 07631
- Englewood Hospital and Medical Center
-
Lakewood, New Jersey, Соединенные Штаты, 08701
- Monmouth Medical Center Southern Campus
-
Long Branch, New Jersey, Соединенные Штаты, 07740
- Monmouth Medical Center
-
Middletown, New Jersey, Соединенные Штаты, 07748
- Memorial Sloan Kettering Monmouth
-
Montvale, New Jersey, Соединенные Штаты, 07645
- Memorial Sloan Kettering Bergen
-
New Brunswick, New Jersey, Соединенные Штаты, 08903
- Rutgers Cancer Institute of New Jersey
-
Newark, New Jersey, Соединенные Штаты, 07112
- Newark Beth Israel Medical Center
-
Toms River, New Jersey, Соединенные Штаты, 08755
- Community Medical Center
-
-
New York
-
Buffalo, New York, Соединенные Штаты, 14263
- Roswell Park Cancer Institute
-
Commack, New York, Соединенные Штаты, 11725
- Memorial Sloan Kettering Commack
-
Glens Falls, New York, Соединенные Штаты, 12801
- Glens Falls Hospital
-
Harrison, New York, Соединенные Штаты, 10604
- Memorial Sloan Kettering Westchester
-
Mineola, New York, Соединенные Штаты, 11501
- NYU Langone Hospital - Long Island
-
New York, New York, Соединенные Штаты, 10065
- Memorial Sloan Kettering Cancer Center
-
New York, New York, Соединенные Штаты, 10032
- NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
-
New York, New York, Соединенные Штаты, 10065
- NYP/Weill Cornell Medical Center
-
New York, New York, Соединенные Штаты, 10016
- Laura and Isaac Perlmutter Cancer Center at NYU Langone
-
Oswego, New York, Соединенные Штаты, 13126
- Upstate Cancer Center at Oswego
-
Syracuse, New York, Соединенные Штаты, 13210
- State University of New York Upstate Medical University
-
Uniondale, New York, Соединенные Штаты, 11553
- Memorial Sloan Kettering Nassau
-
Verona, New York, Соединенные Штаты, 13478
- Upstate Cancer Center at Verona
-
-
North Carolina
-
Chapel Hill, North Carolina, Соединенные Штаты, 27599
- UNC Lineberger Comprehensive Cancer Center
-
-
Ohio
-
Cleveland, Ohio, Соединенные Штаты, 44195
- Cleveland Clinic Foundation
-
Cleveland, Ohio, Соединенные Штаты, 44111
- Cleveland Clinic Cancer Center/Fairview Hospital
-
Columbus, Ohio, Соединенные Штаты, 43210
- Ohio State University Comprehensive Cancer Center
-
Dayton, Ohio, Соединенные Штаты, 45415
- Dayton Physician LLC - Englewood
-
Independence, Ohio, Соединенные Штаты, 44131
- Cleveland Clinic Cancer Center Independence
-
Kettering, Ohio, Соединенные Штаты, 45409
- Greater Dayton Cancer Center
-
Mansfield, Ohio, Соединенные Штаты, 44906
- Cleveland Clinic Cancer Center Mansfield
-
Mayfield Heights, Ohio, Соединенные Штаты, 44124
- Hillcrest Hospital Cancer Center
-
Sandusky, Ohio, Соединенные Штаты, 44870
- North Coast Cancer Care
-
Strongsville, Ohio, Соединенные Штаты, 44136
- Cleveland Clinic Cancer Center Strongsville
-
Warrensville Heights, Ohio, Соединенные Штаты, 44122
- South Pointe Hospital
-
Wooster, Ohio, Соединенные Штаты, 44691
- Cleveland Clinic Wooster Family Health and Surgery Center
-
-
Oklahoma
-
Lawton, Oklahoma, Соединенные Штаты, 73505
- Cancer Centers of Southwest Oklahoma Research
-
Oklahoma City, Oklahoma, Соединенные Штаты, 73104
- University of Oklahoma Health Sciences Center
-
-
Oregon
-
Portland, Oregon, Соединенные Штаты, 97225
- Providence Saint Vincent Medical Center
-
Portland, Oregon, Соединенные Штаты, 97239
- Portland VA Medical Center
-
-
South Carolina
-
Charleston, South Carolina, Соединенные Штаты, 29425
- Medical University of South Carolina
-
Greenville, South Carolina, Соединенные Штаты, 29607
- Saint Francis Cancer Center
-
Greenville, South Carolina, Соединенные Штаты, 29601
- Saint Francis Hospital
-
-
Tennessee
-
Memphis, Tennessee, Соединенные Штаты, 38120
- Baptist Memorial Hospital and Cancer Center-Memphis
-
-
Utah
-
Salt Lake City, Utah, Соединенные Штаты, 84112
- Huntsman Cancer Institute/University of Utah
-
Salt Lake City, Utah, Соединенные Штаты, 84148
- George E Wahlen Department of Veterans Affairs Medical Center
-
-
Virginia
-
Charlottesville, Virginia, Соединенные Штаты, 22908
- University of Virginia Cancer Center
-
Fairfax, Virginia, Соединенные Штаты, 22031
- Inova Schar Cancer Institute
-
Richmond, Virginia, Соединенные Штаты, 23298
- VCU Massey Comprehensive Cancer Center
-
-
Washington
-
Bellevue, Washington, Соединенные Штаты, 98004
- FHCC Overlake
-
Kirkland, Washington, Соединенные Штаты, 98034
- FHCC at EvergreenHealth
-
Seattle, Washington, Соединенные Штаты, 98133
- FHCC at Northwest Hospital
-
-
West Virginia
-
Charleston, West Virginia, Соединенные Штаты, 25304
- Vandalia Health/CAMC Institute for Academic Medicine
-
-
Wisconsin
-
Ashland, Wisconsin, Соединенные Штаты, 54806
- Duluth Clinic Ashland
-
Eau Claire, Wisconsin, Соединенные Штаты, 54701
- Marshfield Medical Center-EC Cancer Center
-
Green Bay, Wisconsin, Соединенные Штаты, 54301
- Saint Vincent Hospital Cancer Center Green Bay
-
Green Bay, Wisconsin, Соединенные Штаты, 54303
- Saint Vincent Hospital Cancer Center at Saint Mary's
-
La Crosse, Wisconsin, Соединенные Штаты, 54601
- Gundersen Lutheran Medical Center
-
Marshfield, Wisconsin, Соединенные Штаты, 54449
- Marshfield Medical Center-Marshfield
-
Minocqua, Wisconsin, Соединенные Штаты, 54548
- Marshfield Medical Center - Minocqua
-
Oconto Falls, Wisconsin, Соединенные Штаты, 54154
- Saint Vincent Hospital Cancer Center at Oconto Falls
-
Rice Lake, Wisconsin, Соединенные Штаты, 54868
- Marshfield Medical Center-Rice Lake
-
Sheboygan, Wisconsin, Соединенные Штаты, 53081
- Saint Vincent Hospital Cancer Center at Sheboygan
-
Stevens Point, Wisconsin, Соединенные Штаты, 54482
- Marshfield Medical Center-River Region at Stevens Point
-
Sturgeon Bay, Wisconsin, Соединенные Штаты, 54235-1495
- Saint Vincent Hospital Cancer Center at Sturgeon Bay
-
Weston, Wisconsin, Соединенные Штаты, 54476
- Marshfield Medical Center - Weston
-
-
Критерии участия
Критерии приемлемости
Возраст, подходящий для обучения
Принимает здоровых добровольцев
Полы, имеющие право на обучение
Описание
Inclusion Criteria:
-
Participants must have histologically or cytologically confirmed diffuse large B-cell lymphoma (DLBCL), Ann Arbor Stage IIX (bulky), III or IV. Participants with DLBCL transformed from follicular lymphoma (FL) or marginal zone lymphoma (MZL, including mucosa-associated lymphoid tissue [MALT] lymphomas), lymphoplasmacytic lymphoma (LPL), or nodular lymphocyte-predominant Hodgkin Lymphoma (NLPHL) are eligible. Participants with Grade IIIB follicular lymphoma (FL) or high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements are also eligible. Participants with DLBCL that arose from prior CLL (Richter's transformation) are not eligible.
-
As defined by the World Health Organization (WHO), eligible lymphoma subtypes include the following:
- DLBCL, not otherwise specified (NOS)
- DLBCL, germinal-center B-cell type (GCB)
- DLBCL, activated B-cell type (ABC)
- T-cell histiocyte-rich B-cell lymphomas (THRBCL)
- Primary cutaneous DLBCL, leg type
- Intravascular large B cell lymphoma
- EBV+ DLBCL, NOS
- DLBCL associated with chronic inflammation
- HHV8+ DLBCL, NOS
- High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements
- High grade B-cell lymphoma, NOS
- Follicular lymphoma grade 3b
-
Participants must have staging imaging performed within 28 days prior to registration, as follows. PET-CT baseline scans are strongly preferred; diagnostic quality magnetic resonance imaging (MRI), contrast-enhanced CT, or contrast-enhanced MRI scans are also acceptable if PET-CT is not feasible at baseline. Note: PET-CT will be required at end of treatment (EOT) and progression for response assessment. Participants must have measurable disease (at least one lesion with longest diameter ≥ 1.5 cm). All measurable lesions (longest diameter >= 1.5 cm) must be assessed within 28 days prior to registration. Tests to assess non-measurable disease must be performed within 42 days prior to registration.
-
Participants with known human immunodeficiency virus (HIV)-infection are eligible providing they are on effective anti-retroviral therapy and have undetectable viral load at their most recent viral load test (must be within 26 weeks prior to registration). Participants with known HIV must have a CD4 count checked within 28 days prior to registration, but may proceed with therapy regardless of CD4 count.
-
All participants must be screened for chronic hepatitis B virus (HBV) within 28 days prior to registration. Participants with known HBV infection (positive serology) must also have a HBV viral load performed within 28 days prior to registration, and participants must have an undetectable HBV viral load on suppressive therapy within 28 days prior to registration. Participants found to be HBV carriers during screening are eligible and must receive standard of care prophylaxis. Participants with active hepatitis B (HBV viral load > 500 IU/mL) within 28 days prior to registration are not eligible
-
Participants with a known history of hepatitis C virus (HCV) infection must have an undetectable HCV viral load within in 28 days prior to registration
-
Participants must not have known lymphomatous involvement of the central nervous system (CNS)
-
Participants must not have active inflammatory bowel disease (such as, Crohn's disease, ulcerative colitis), celiac disease (i.e., sprue), prior gastrectomy or upper bowel removal, or any other gastrointestinal disorder or defect that would interfere with the absorption, distribution, metabolism, or excretion of the study drug and/or predispose the subject to an increased risk of gastrointestinal toxicity
-
Participants must not have a history of acute leukemia having been treated with intensive induction therapy. Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
-
Participants must not have received any prior cytotoxic chemotherapy or rituximab for treatment of the newly diagnosed DLBCL except for the pre-phase treatment (within specified dose range) that may have either started before or may start after registration to S1918. Inhaled, nasal, and topical steroid use is allowed. Prior cytotoxic chemotherapy and/or antibody therapy for an indolent lymphoma prior to transformation is allowed. Up to 4 doses of intrathecal (IT) chemotherapy administered for central nervous system (CNS) prophylaxis is allowed in addition to protocol therapy. High-dose intravenous methotrexate is not allowed.
-
Participants must not have received more than a cumulative of dose 250 mg/m^2 of prior doxorubicin (or equivalent dose of another anthracycline, such as epirubicin) therapy (at any time prior to registration).
-
Participants must not currently be receiving any other investigational agents
-
Participant must not have a history of allergic reactions attributed to azacitidine, mannitol, or other hypomethylating agents
-
Participants must be age ≥ 75
-
Participants must have a Zubrod performance status of 0-2
-
Participants must have adequate renal function, as demonstrated by a creatinine clearance, calculated by the Cockcroft and Gault formula, of >= 30 ml/min that was obtained within 28 days prior to registration
-
Aspartate aminotransferase (AST) =< 2.5 x institutional upper limit of normal (IULN), alanine aminotransferase (ALT) =< 2.5 x IULN (within 28 days prior to registration)
-
Total bilirubin =< 2 x institutional upper limit of normal (IULN), unless due to Gilbert's disease, hemolysis, or lymphomatous involvement of liver (within 28 days prior to registration). Note: If total bilirubin is elevated, and direct bilirubin is subsequently performed (within 28 days prior to registration) and resulted to be =< 2 x IULN, the participant will be considered eligible
-
Absolute neutrophil count (ANC) >= 1000/mcL (within 28 days prior to registration)
-
Platelets >= 75,000/mcL (within 28 days prior to registration)
-
Hemoglobin (Hgb) >= 8 g/ dL (within 28 days prior to registration)
-
If there is a documented lymphomatous involvement of the bone marrow, bone marrow function within 28 days prior to registration, as evidenced by:
- ANC >= 500/mcL
- Platelets >= 50,000/mcL
- Hgb >= 8 g/ dL
-
Participants must have a left ventricular ejection (LVEF) fraction >= 45% as measured by echocardiogram or radionuclide (multigated acquisition scan [MUGA]) ventriculography within 56 days prior to registration
-
For the duration of the study treatment period and for at least 4 months following the last dose of study drug, male participants must agree to use effective contraceptive methods during sexual contact with a female of childbearing potential (FCBP) and must agree to refrain from semen or sperm donation during the same timeframe. Effective contraceptive methods include a history of vasectomy, use of hormonal contraception or an intrauterine device (IUD) by the female partner, or use of condoms
- A FCBP is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
-
Participants must not have active infection (systemic fungal, bacterial, or viral infection) that is not controlled (defined as ongoing signs/symptoms related the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment)
-
Participants must not have active cardiac disease within 26 weeks prior to registration, including: symptomatic congestive heart failure (New York Heart Association [NYHA] class 4), unstable angina pectoris, hemodynamically unstable cardiac arrhythmia, or myocardial infarction
-
Participants must not have >= grade 2 neuropathy, by Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 5.0, within 28 days prior to registration
-
Participants must not have any other known uncontrolled intercurrent illness including, but not limited to ongoing psychiatric illness/social situations that would limit compliance with study requirements
-
Participants must not have a concurrent primary malignancy undergoing active therapy. Exceptions: participants may have non-melanomatous skin cancers requiring only surgical intervention. Participants may have a history of early stage breast cancer or prostate cancer in remission after surgical and/or radiation therapy on adjuvant hormonal therapy only
Учебный план
Как устроено исследование?
Детали дизайна
- Основная цель: Уход
- Распределение: Рандомизированный
- Интервенционная модель: Параллельное назначение
- Маскировка: Нет (открытая этикетка)
Оружие и интервенции
Группа участников / Армия |
Вмешательство/лечение |
|---|---|
|
Экспериментальный: Arm I (oral azacitidine, R-miniCHOP)
Patients receive CC-486 PO for 7 days prior to cycle 1. Patients then receive CC-486 PO on days 8-21. Treatment repeats every 21 days for cycles 1-5 in the absence of disease progression or unacceptable toxicity. Patients also receive rituximab IV (or rituximab and hyaluronidase human SC for cycles 2-6), cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 1, and prednisone PO on days 1-5. Treatment repeats every 21 days for cycles 1-6 (6 cycles total) in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO or MUGA at screening and undergo PET-CT and blood sample collection throughout the study. |
Given IV
Другие имена:
Given IV
Другие имена:
Given PO
Другие имена:
Undergo blood sample collection
Другие имена:
Given IV
Другие имена:
Given IV
Другие имена:
Ancillary studies Undergo ECHO
Другие имена:
Undergo MUGA
Другие имена:
Undergo PET-CT
Другие имена:
Given SC
Другие имена:
Undergo PET-CT
Другие имена:
Given PO
Другие имена:
|
|
Активный компаратор: Arm II (R-miniCHOP)
Patients receive rituximab IV (or rituximab and hyaluronidase human SC for cycles 2-6), cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 1, and prednisone PO on days 1-5. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO or MUGA at screening and undergo PET-CT and blood sample collection throughout the study. |
Given IV
Другие имена:
Given IV
Другие имена:
Given PO
Другие имена:
Undergo blood sample collection
Другие имена:
Given IV
Другие имена:
Given IV
Другие имена:
Ancillary studies Undergo ECHO
Другие имена:
Undergo MUGA
Другие имена:
Undergo PET-CT
Другие имена:
Given SC
Другие имена:
Undergo PET-CT
Другие имена:
|
Что измеряет исследование?
Первичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
|
Excess toxicity as a result of adding oral azacitidine (CC-486) to reduced dose rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone (R-miniCHOP) (Safety run-in)
Временное ограничение: Up to completion of cycle 6
|
Will determine if the addition of CC-486 to R-miniCHOP results in excess toxicity compared to R-miniCHOP alone that would preclude the combination from being studied further. |
Up to completion of cycle 6
|
|
Progression-free survival (PFS) (Phase II)
Временное ограничение: From date of registration to date of first observation of progressive disease according to the 2014 Lugano classification, or death due to any cause, assessed up to 1 year
|
Will determine if the CC-486 + R-miniCHOP regimen should be tested further (Phase III) against the control R-miniCHOP alone based on PFS. After accruing 130 patients (65 per arm, 21 months of accrual and potentially pausing accrual for 6 months follow-up to reach a target 63 events across arms), a one-sided stratified .10 log-rank test will inform a go/no-go decision based on sufficient evidence of efficacy to continue to the Phase III portion of the study. |
From date of registration to date of first observation of progressive disease according to the 2014 Lugano classification, or death due to any cause, assessed up to 1 year
|
|
Overall survival (Phase III)
Временное ограничение: From date of registration to date of death due to any cause, assessed up to 2 years
|
Will compare overall survival in the control arm of R-miniCHOP to the experimental arm of CC-486 (oral azacitidine) + R-miniCHOP. Will be evaluated using a 1-sided .025 level stratified logrank test. |
From date of registration to date of death due to any cause, assessed up to 2 years
|
Вторичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
|
Metabolic complete response (CR)
Временное ограничение: Up to end of cycle 6 or end of treatment
|
Will be defined using 2014 Lugano classification. Fisher's exact test will be used to compare CR rates between the experimental arm of CC-486 + R-miniCHOP and the control arm of R-miniCHOP alone. |
Up to end of cycle 6 or end of treatment
|
|
Incidence of adverse events
Временное ограничение: Until disease progression, assessed up to 5 years
|
Will be assessed using Common Terminology Criteria for Adverse Events version 5. The maximum Grade for each toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns. Treatment-related toxicities between arms will be compared using Fisher's exact test. |
Until disease progression, assessed up to 5 years
|
|
Overall survival (Phase III)
Временное ограничение: From date of registration to date of death due to any cause, assessed up to 5 years
|
An additional secondary analysis of overall survival of the Phase III comparison will adjust for patients with identified double-hit phenotype in addition to the pre-specified stratification factors. Will also prospectively collect the number of days between diagnostic biopsy and cycle 1 day 1 of therapy for a pre-planned secondary analysis. |
From date of registration to date of death due to any cause, assessed up to 5 years
|
Другие показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
|
Changes in function (Integrated Correlative Geriatric Assessments Substudy)
Временное ограничение: From time of randomization up to 24 months after date of registration
|
Will be assessed by a Comprehensive Geriatric Assessment (Carolina Frailty Index [CFI] Score) between patients treated with CC-486 + R-miniCHOP and those treated with R-miniCHOP alone. Linear regression will be used for each examination, adjusting for the stratification factors from the clinical study and the baseline score (for the examination of change from 12 to 24 months, the 12-month score will be considered the baseline score). Although the number of timepoints is limited to 3, longitudinal assessments of the CFI Score over time will also be conducted using linear mixed models, adjusting for the stratification factors and the baseline score, with patient considered a random effect. |
From time of randomization up to 24 months after date of registration
|
|
Frailty status (fit/unfit vs frail) (Integrated Correlative Geriatric Assessments Substudy)
Временное ограничение: Baseline
|
Will evaluate if frailty status (fit/unfit versus frail) as assessed by the Italian Lymphoma Foundation (FIL) tool is associated with overall survival. Multivariable Cox regression will be conducted, adjusting for the stratification variables and the randomized treatment arm as covariates. Will also examine whether randomization to CC-486 + R-miniCHOP is associated with better overall survival compared to treatment with R-miniCHOP alone in the subset of fit and unfit patients. Multivariable Cox regression will be conducted, adjusting for the stratification variables as covariates. |
Baseline
|
|
Frailty status (Integrated Correlative Geriatric Assessments Substudy)
Временное ограничение: Up to 24 months after date of registration
|
Will evaluate if frailty status (fit/unfit versus frail) as assessed by the FIL tool correlates with the summary frailty indexed as measured by the S1918 Comprehensive Geriatric Assessment (CGA). In particular, agreement between the FIL and CGA will measured using an unweighted Kappa statistic; moderate or better agreement is defined as a Kappa coefficient of >= 0.41. |
Up to 24 months after date of registration
|
Соавторы и исследователи
Спонсор
Следователи
- Главный следователь: Elizabeth A Brem, SWOG Cancer Research Network
Публикации и полезные ссылки
Даты записи исследования
Изучение основных дат
Начало исследования (Действительный)
Первичное завершение (Оцененный)
Завершение исследования (Оцененный)
Даты регистрации исследования
Первый отправленный
Впервые представлено, что соответствует критериям контроля качества
Первый опубликованный (Действительный)
Обновления учебных записей
Последнее опубликованное обновление (Действительный)
Последнее отправленное обновление, отвечающее критериям контроля качества
Последняя проверка
Дополнительная информация
Термины, связанные с этим исследованием
Дополнительные соответствующие термины MeSH
- Новообразования
- Заболевания иммунной системы
- Новообразования по гистологическому типу
- Лимфатические заболевания
- Лимфопролиферативные заболевания
- Иммунопролиферативные заболевания
- Лимфома, неходжкинская
- Лимфома, В-клеточная
- Лимфома
- Гемики и лимфатические заболевания
- Лимфома, крупная В-клеточная, диффузная
- Лимфома, B-клетки, маргинальная зона
- Аминокислоты, пептиды и белки
- Белки
- Органические химические вещества
- Гетероциклические соединения, 1-кольцо
- Гетероциклические соединения
- Гетероциклические соединения, 2-кольцо
- Гетероциклические соединения, слитое кольцо
- Следственные методы
- Клинические лабораторные методы
- Диагностические методы и процедуры
- Диагноз
- Нуклеиновые кислоты, нуклеотиды и нуклеозиды
- Углеводороды
- Углеводороды, циклические
- Углеводы
- Алкалоиды
- Полициклические ароматические углеводороды
- Углеводороды, ароматные
- Полициклические соединения
- Гликозиды
- Гликозид -гидролазы
- Гидролазы
- Ферменты
- Ферменты и коэнзименты
- Полисахарид-лиазы
- Углеродистые лиязы
- Лиазы
- Индолы
- Антитела, моноклональные
- Антитела
- Иммуноглобулины
- Иммунопротеины
- Белки крови
- Сывороточные глобулины
- Глобулины
- Цитидин
- Пиримидиновые нуклеозиды
- Пиримидины
- Беременные
- Беременные
- Стероиды
- Соединения слитого кольца
- Химические методы, аналитические
- Анализ спектра
- Фосфорамид горчицы
- Азотные соединения горчицы
- Горчичные соединения
- Углеводороды, галогенированные
- Фосфорамиды
- Соединения органофосфора
- Aza Compounds
- Нуклеозиды
- Рибонуклеозиды
- Беременные
- VINCA ALKALOIDS
- Секологические триптаминовые алкалоиды
- Индольные алкалоиды
- Индолизидины
- Индолизины
- Антрациклины
- Нафтацены
- Аминогликозиды
- Антитела, моноклональные, происходящие из мыши
- Даунорубицин
- Ритуксимаб
- Преднизолон
- Циклофосфамид
- Азацитидин
- Доксорубицин
- Винкристин
- Гиалуроноглюкозаминидаза
- Обработка образца
- Магнитно -резонансная спектроскопия
- CC-486
- CT-P10
- Дельтакортен
- Предснилиден
Другие идентификационные номера исследования
- NCI-2020-01256
- U10CA180888 (Грант/контракт NIH США)
- NCI-2020-01256 (Идентификатор реестра: CTRP (Clinical Trial Reporting Program))
- S1918 (Другой идентификатор: CTEP)
- S1918 (Другой идентификатор: SWOG)
Планирование данных отдельных участников (IPD)
Планируете делиться данными об отдельных участниках (IPD)?
Описание плана IPD
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.
Информация о лекарствах и устройствах, исследовательские документы
Изучает лекарственный продукт, регулируемый FDA США.
Изучает продукт устройства, регулируемый Управлением по санитарному надзору за качеством пищевых продуктов и медикаментов США.
Эта информация была получена непосредственно с веб-сайта clinicaltrials.gov без каких-либо изменений. Если у вас есть запросы на изменение, удаление или обновление сведений об исследовании, обращайтесь по адресу register@clinicaltrials.gov. Как только изменение будет реализовано на clinicaltrials.gov, оно будет автоматически обновлено и на нашем веб-сайте. .