Test du CC-486 (azacitidine orale) plus le traitement médicamenteux standard chez les patients de 75 ans ou plus atteints d'un lymphome diffus à grandes cellules B nouvellement diagnostiqué
Une étude randomisée de phase II/III de R-MiniCHOP avec ou sans CC-486 (azacitidine orale) chez des participants âgés de 75 ans ou plus atteints d'un lymphome diffus à grandes cellules B nouvellement diagnostiqué, d'un lymphome folliculaire de grade IIIB, d'un lymphome transformé et d'un lymphome B de haut grade - Lymphomes cellulaires avec réarrangements MYC ET BCL2 et/ou 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.
Aperçu de l'étude
Statut
Les conditions
- Lymphome lymphoplasmocytaire
- Lymphome diffus à grandes cellules B d'Ann Arbor de stade III
- Lymphome diffus à grandes cellules B d'Ann Arbor de stade IV
- Lymphome à cellules B de haut grade avec réarrangements MYC et BCL2 ou BCL6
- Lymphome à cellules B de haut grade avec réarrangements MYC, BCL2 et BCL6
- Lymphome folliculaire de grade 3b
- Lymphome diffus à grandes cellules B, non spécifié ailleurs
- Lymphome diffus à grandes cellules B positif pour l'EBV, non spécifié ailleurs
- Lymphome à cellules B de haut grade, non spécifié ailleurs
- Lymphome diffus à grandes cellules B associé à une inflammation chronique
- Lymphome cutané diffus primitif à grandes cellules B, type jambe
- Lymphome folliculaire transformé en lymphome diffus à grandes cellules B
- Lymphome intravasculaire à grandes cellules B
- Lymphome à grandes cellules B riche en cellules T/histiocytes
- Lymphome à cellules B de haut grade avec réarrangements MYC et BCL2 et/ou BCL6
- Lymphome B diffus à grandes cellules de type B activé
- Lymphome diffus à grandes cellules B Centre germinal de type cellule B
- Lymphome diffus à grandes cellules B positif au HHV8, non spécifié ailleurs
- Lymphome de la zone marginale transformé en lymphome diffus à grandes cellules B
- Lymphome diffus à grandes cellules B d'Ann Arbor stade IIX (volumineux)
- Lymphome nodulaire à lymphocytes B à prédominance lymphocytaire
Intervention / Traitement
- Médicament: Cyclophosphamide
- Médicament: Doxorubicin Hydrochloride
- Médicament: Prednisone
- Procédure: Biospecimen Collection
- Biologique: Rituximab
- Médicament: Vincristine Sulfate
- Autre: Questionnaire Administration
- Procédure: Echocardiography Test
- Procédure: Multigated Acquisition Scan
- Procédure: Positron Emission Tomography
- Biologique: Rituximab and Hyaluronidase Human
- Procédure: Computed Tomography
- Médicament: Oral Azacitidine
Description détaillée
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.
Type d'étude
Inscription (Estimé)
Phase
- Phase 2
- Phase 3
Contacts et emplacements
Lieux d'étude
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Arizona
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Tucson, Arizona, États-Unis, 85719
- Banner University Medical Center - Tucson
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Tucson, Arizona, États-Unis, 85719
- University of Arizona Cancer Center-North Campus
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Arkansas
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Little Rock, Arkansas, États-Unis, 72205
- University of Arkansas for Medical Sciences
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California
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Anaheim, California, États-Unis, 92806
- Kaiser Permanente-Anaheim
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Baldwin Park, California, États-Unis, 91706
- Kaiser Permanente-Baldwin Park
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Bellflower, California, États-Unis, 90706
- Kaiser Permanente-Bellflower
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Beverly Hills, California, États-Unis, 90211
- Tower Cancer Research Foundation
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Costa Mesa, California, États-Unis, 92627
- UC Irvine Health Cancer Center-Newport
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Duarte, California, États-Unis, 91010
- City of Hope Comprehensive Cancer Center
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Fontana, California, États-Unis, 92335
- Kaiser Permanente-Fontana
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Harbor City, California, États-Unis, 90710
- Kaiser Permanente South Bay
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Huntington Beach, California, États-Unis, 92648
- City of Hope Seacliff
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Irvine, California, États-Unis, 92618
- Kaiser Permanente-Irvine
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Irvine, California, États-Unis, 92618
- City of Hope at Irvine Lennar
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Lancaster, California, États-Unis, 93534
- City of Hope Antelope Valley
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Long Beach, California, États-Unis, 90822
- Tibor Rubin VA Medical Center
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Long Beach, California, États-Unis, 90813
- City of Hope at Long Beach Elm
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Los Angeles, California, États-Unis, 90048
- Cedars-Sinai Medical Center
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Los Angeles, California, États-Unis, 90027
- Kaiser Permanente Los Angeles Medical Center
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Los Angeles, California, États-Unis, 90034
- Kaiser Permanente West Los Angeles
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Newport Beach, California, États-Unis, 92660
- City of Hope Newport Beach
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Ontario, California, États-Unis, 91761
- Kaiser Permanente-Ontario
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Orange, California, États-Unis, 92868
- UC Irvine Health/Chao Family Comprehensive Cancer Center
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Palo Alto, California, États-Unis, 94304
- Stanford Cancer Institute Palo Alto
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Panorama City, California, États-Unis, 91402
- Kaiser Permanente - Panorama City
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Riverside, California, États-Unis, 92505
- Kaiser Permanente-Riverside
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San Diego, California, États-Unis, 92120
- Kaiser Permanente-San Diego Zion
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San Marcos, California, États-Unis, 92078
- Kaiser Permanente-San Marcos
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San Mateo, California, États-Unis, 94402
- UCSF Cancer Center - San Mateo
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South Pasadena, California, États-Unis, 91030
- City of Hope South Pasadena
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Torrance, California, États-Unis, 90503
- City of Hope South Bay
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Upland, California, États-Unis, 91786
- City of Hope Upland
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Woodland Hills, California, États-Unis, 91367
- Kaiser Permanente-Woodland Hills
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Colorado
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Golden, Colorado, États-Unis, 80401
- Lutheran Hospital - Cancer Centers of Colorado
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Delaware
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Newark, Delaware, États-Unis, 19713
- Helen F Graham Cancer Center
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Newark, Delaware, États-Unis, 19713
- Delaware Clinical and Laboratory Physicians PA
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Newark, Delaware, États-Unis, 19713
- Medical Oncology Hematology Consultants PA
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Florida
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Miami, Florida, États-Unis, 33136
- University of Miami Miller School of Medicine-Sylvester Cancer Center
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Georgia
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Atlanta, Georgia, États-Unis, 30308
- Emory University Hospital Midtown
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Atlanta, Georgia, États-Unis, 30322
- Emory University Hospital/Winship Cancer Institute
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Atlanta, Georgia, États-Unis, 30342
- Emory Saint Joseph's Hospital
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Augusta, Georgia, États-Unis, 30912
- Augusta University Medical Center
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Hawaii
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Honolulu, Hawaii, États-Unis, 96813
- Queen's Medical Center
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Honolulu, Hawaii, États-Unis, 96813
- Hawaii Cancer Care Inc - Waterfront Plaza
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Honolulu, Hawaii, États-Unis, 96813
- Queen's Cancer Cenrer - POB I
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Honolulu, Hawaii, États-Unis, 96813
- Straub Clinic and Hospital
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Honolulu, Hawaii, États-Unis, 96817
- Queen's Cancer Center - Kuakini
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‘Aiea, Hawaii, États-Unis, 96701
- Hawaii Cancer Care - Westridge
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‘Aiea, Hawaii, États-Unis, 96701
- Pali Momi Medical Center
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Illinois
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Centralia, Illinois, États-Unis, 62801
- Centralia Oncology Clinic
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Chicago, Illinois, États-Unis, 60611
- Northwestern University
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Chicago, Illinois, États-Unis, 60637
- University of Chicago Comprehensive Cancer Center
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Chicago, Illinois, États-Unis, 60612
- University of Illinois
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Danville, Illinois, États-Unis, 61832
- Carle at The Riverfront
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DeKalb, Illinois, États-Unis, 60115
- Northwestern Medicine Cancer Center Kishwaukee
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Decatur, Illinois, États-Unis, 62526
- Decatur Memorial Hospital
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Decatur, Illinois, États-Unis, 62526
- Cancer Care Specialists of Illinois - Decatur
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Effingham, Illinois, États-Unis, 62401
- Crossroads Cancer Center
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Effingham, Illinois, États-Unis, 62401
- Carle Physician Group-Effingham
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Evanston, Illinois, États-Unis, 60201
- NorthShore University HealthSystem-Evanston Hospital
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Geneva, Illinois, États-Unis, 60134
- Northwestern Medicine Cancer Center Delnor
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Glenview, Illinois, États-Unis, 60026
- NorthShore University HealthSystem-Glenbrook Hospital
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Glenview, Illinois, États-Unis, 60026
- Northwestern Medicine Glenview Outpatient Center
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Grayslake, Illinois, États-Unis, 60030
- Northwestern Medicine Grayslake Outpatient Center
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Highland Park, Illinois, États-Unis, 60035
- NorthShore University HealthSystem-Highland Park Hospital
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Lake Forest, Illinois, États-Unis, 60045
- Northwestern Medicine Lake Forest Hospital
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Mattoon, Illinois, États-Unis, 61938
- Carle Physician Group-Mattoon/Charleston
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New Lenox, Illinois, États-Unis, 60451
- UC Comprehensive Cancer Center at Silver Cross
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O'Fallon, Illinois, États-Unis, 62269
- Cancer Care Center of O'Fallon
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Orland Park, Illinois, États-Unis, 60462
- University of Chicago Medicine-Orland Park
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Orland Park, Illinois, États-Unis, 60462
- Northwestern Medicine Orland Park
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Peoria, Illinois, États-Unis, 61615
- Illinois CancerCare-Peoria
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Shiloh, Illinois, États-Unis, 62269
- Memorial Hospital East
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Urbana, Illinois, États-Unis, 61801
- Carle Cancer Center
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Warrenville, Illinois, États-Unis, 60555
- Northwestern Medicine Cancer Center Warrenville
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Iowa
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Ames, Iowa, États-Unis, 50010
- McFarland Clinic - Ames
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Ankeny, Iowa, États-Unis, 50023
- UI Health Care Mission Cancer and Blood - Ankeny Clinic
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Clive, Iowa, États-Unis, 50325
- UI Health Care Mission Cancer and Blood - West Des Moines Clinic
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Des Moines, Iowa, États-Unis, 50309
- Iowa Methodist Medical Center
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Des Moines, Iowa, États-Unis, 50309
- UI Health Care Mission Cancer and Blood - Des Moines Clinic
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Des Moines, Iowa, États-Unis, 50314
- UI Health Care Mission Cancer and Blood - Laurel Clinic
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Louisiana
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Monroe, Louisiana, États-Unis, 71202
- Ochsner LSU Health Monroe Medical Center
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Shreveport, Louisiana, États-Unis, 71103
- LSU Health Sciences Center at Shreveport
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Massachusetts
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Boston, Massachusetts, États-Unis, 02111
- Tufts Medical Center
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Michigan
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Ann Arbor, Michigan, États-Unis, 48106
- Trinity Health Saint Joseph Mercy Hospital Ann Arbor
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Brighton, Michigan, États-Unis, 48114
- Trinity Health IHA Medical Group Hematology Oncology - Brighton
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Brighton, Michigan, États-Unis, 48114
- Trinity Health Medical Center - Brighton
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Canton, Michigan, États-Unis, 48188
- Trinity Health IHA Medical Group Hematology Oncology - Canton
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Canton, Michigan, États-Unis, 48188
- Trinity Health Medical Center - Canton
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Chelsea, Michigan, États-Unis, 48118
- Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
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Chelsea, Michigan, États-Unis, 48118
- Chelsea Hospital
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Livonia, Michigan, États-Unis, 48154
- Trinity Health Saint Mary Mercy Livonia Hospital
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Livonia, Michigan, États-Unis, 48154
- Hope Cancer Clinic
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Ypsilanti, Michigan, États-Unis, 48197
- Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
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Ypsilanti, Michigan, États-Unis, 48106
- Huron Gastroenterology PC
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Minnesota
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Deer River, Minnesota, États-Unis, 56636
- Essentia Health - Deer River Clinic
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Duluth, Minnesota, États-Unis, 55805
- Essentia Health Cancer Center
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Hibbing, Minnesota, États-Unis, 55746
- Essentia Health Hibbing Clinic
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Sandstone, Minnesota, États-Unis, 55072
- Essentia Health Sandstone
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Virginia, Minnesota, États-Unis, 55792
- Essentia Health Virginia Clinic
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Mississippi
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Oxford, Mississippi, États-Unis, 38655
- Baptist Memorial Hospital and Cancer Center-Oxford
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Southhaven, Mississippi, États-Unis, 38671
- Baptist Memorial Hospital and Cancer Center-Desoto
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Missouri
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Cape Girardeau, Missouri, États-Unis, 63703
- Saint Francis Medical Center
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Chesterfield, Missouri, États-Unis, 63017
- Saint Luke's Hospital
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City of Saint Peters, Missouri, États-Unis, 63376
- Siteman Cancer Center at Saint Peters Hospital
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Creve Coeur, Missouri, États-Unis, 63141
- Siteman Cancer Center at West County Hospital
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Saint Joseph, Missouri, États-Unis, 64506
- Heartland Regional Medical Center
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St Louis, Missouri, États-Unis, 63110
- Washington University School of Medicine
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St Louis, Missouri, États-Unis, 63129
- Siteman Cancer Center-South County
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St Louis, Missouri, États-Unis, 63136
- Siteman Cancer Center at Christian Hospital
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Nebraska
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Lincoln, Nebraska, États-Unis, 68516
- Cancer Partners of Nebraska
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New Jersey
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Basking Ridge, New Jersey, États-Unis, 07920
- Memorial Sloan Kettering Basking Ridge
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Englewood, New Jersey, États-Unis, 07631
- Englewood Hospital and Medical Center
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Lakewood, New Jersey, États-Unis, 08701
- Monmouth Medical Center Southern Campus
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Long Branch, New Jersey, États-Unis, 07740
- Monmouth Medical Center
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Middletown, New Jersey, États-Unis, 07748
- Memorial Sloan Kettering Monmouth
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Montvale, New Jersey, États-Unis, 07645
- Memorial Sloan Kettering Bergen
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New Brunswick, New Jersey, États-Unis, 08903
- Rutgers Cancer Institute of New Jersey
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Newark, New Jersey, États-Unis, 07112
- Newark Beth Israel Medical Center
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Toms River, New Jersey, États-Unis, 08755
- Community Medical Center
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New York
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Buffalo, New York, États-Unis, 14263
- Roswell Park Cancer Institute
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Commack, New York, États-Unis, 11725
- Memorial Sloan Kettering Commack
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Glens Falls, New York, États-Unis, 12801
- Glens Falls Hospital
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Harrison, New York, États-Unis, 10604
- Memorial Sloan Kettering Westchester
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Mineola, New York, États-Unis, 11501
- NYU Langone Hospital - Long Island
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New York, New York, États-Unis, 10065
- Memorial Sloan Kettering Cancer Center
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New York, New York, États-Unis, 10032
- NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
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New York, New York, États-Unis, 10065
- NYP/Weill Cornell Medical Center
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New York, New York, États-Unis, 10016
- Laura and Isaac Perlmutter Cancer Center at NYU Langone
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Oswego, New York, États-Unis, 13126
- Upstate Cancer Center at Oswego
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Syracuse, New York, États-Unis, 13210
- State University of New York Upstate Medical University
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Uniondale, New York, États-Unis, 11553
- Memorial Sloan Kettering Nassau
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Verona, New York, États-Unis, 13478
- Upstate Cancer Center at Verona
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North Carolina
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Chapel Hill, North Carolina, États-Unis, 27599
- UNC Lineberger Comprehensive Cancer Center
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Ohio
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Cleveland, Ohio, États-Unis, 44195
- Cleveland Clinic Foundation
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Cleveland, Ohio, États-Unis, 44111
- Cleveland Clinic Cancer Center/Fairview Hospital
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Columbus, Ohio, États-Unis, 43210
- Ohio State University Comprehensive Cancer Center
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Dayton, Ohio, États-Unis, 45415
- Dayton Physician LLC - Englewood
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Independence, Ohio, États-Unis, 44131
- Cleveland Clinic Cancer Center Independence
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Kettering, Ohio, États-Unis, 45409
- Greater Dayton Cancer Center
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Mansfield, Ohio, États-Unis, 44906
- Cleveland Clinic Cancer Center Mansfield
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Mayfield Heights, Ohio, États-Unis, 44124
- Hillcrest Hospital Cancer Center
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Sandusky, Ohio, États-Unis, 44870
- North Coast Cancer Care
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Strongsville, Ohio, États-Unis, 44136
- Cleveland Clinic Cancer Center Strongsville
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Warrensville Heights, Ohio, États-Unis, 44122
- South Pointe Hospital
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Wooster, Ohio, États-Unis, 44691
- Cleveland Clinic Wooster Family Health and Surgery Center
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Oklahoma
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Lawton, Oklahoma, États-Unis, 73505
- Cancer Centers of Southwest Oklahoma Research
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Oklahoma City, Oklahoma, États-Unis, 73104
- University of Oklahoma Health Sciences Center
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Oregon
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Portland, Oregon, États-Unis, 97225
- Providence Saint Vincent Medical Center
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Portland, Oregon, États-Unis, 97239
- Portland VA Medical Center
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South Carolina
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Charleston, South Carolina, États-Unis, 29425
- Medical University of South Carolina
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Greenville, South Carolina, États-Unis, 29607
- Saint Francis Cancer Center
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Greenville, South Carolina, États-Unis, 29601
- Saint Francis Hospital
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Tennessee
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Memphis, Tennessee, États-Unis, 38120
- Baptist Memorial Hospital and Cancer Center-Memphis
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Utah
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Salt Lake City, Utah, États-Unis, 84112
- Huntsman Cancer Institute/University of Utah
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Salt Lake City, Utah, États-Unis, 84148
- George E Wahlen Department of Veterans Affairs Medical Center
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Virginia
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Charlottesville, Virginia, États-Unis, 22908
- University of Virginia Cancer Center
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Fairfax, Virginia, États-Unis, 22031
- Inova Schar Cancer Institute
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Richmond, Virginia, États-Unis, 23298
- VCU Massey Comprehensive Cancer Center
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Washington
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Bellevue, Washington, États-Unis, 98004
- FHCC Overlake
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Kirkland, Washington, États-Unis, 98034
- FHCC at EvergreenHealth
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Seattle, Washington, États-Unis, 98133
- FHCC at Northwest Hospital
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West Virginia
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Charleston, West Virginia, États-Unis, 25304
- Vandalia Health/CAMC Institute for Academic Medicine
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Wisconsin
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Ashland, Wisconsin, États-Unis, 54806
- Duluth Clinic Ashland
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Eau Claire, Wisconsin, États-Unis, 54701
- Marshfield Medical Center-EC Cancer Center
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Green Bay, Wisconsin, États-Unis, 54301
- Saint Vincent Hospital Cancer Center Green Bay
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Green Bay, Wisconsin, États-Unis, 54303
- Saint Vincent Hospital Cancer Center at Saint Mary's
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La Crosse, Wisconsin, États-Unis, 54601
- Gundersen Lutheran Medical Center
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Marshfield, Wisconsin, États-Unis, 54449
- Marshfield Medical Center-Marshfield
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Minocqua, Wisconsin, États-Unis, 54548
- Marshfield Medical Center - Minocqua
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Oconto Falls, Wisconsin, États-Unis, 54154
- Saint Vincent Hospital Cancer Center at Oconto Falls
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Rice Lake, Wisconsin, États-Unis, 54868
- Marshfield Medical Center-Rice Lake
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Sheboygan, Wisconsin, États-Unis, 53081
- Saint Vincent Hospital Cancer Center at Sheboygan
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Stevens Point, Wisconsin, États-Unis, 54482
- Marshfield Medical Center-River Region at Stevens Point
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Sturgeon Bay, Wisconsin, États-Unis, 54235-1495
- Saint Vincent Hospital Cancer Center at Sturgeon Bay
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Weston, Wisconsin, États-Unis, 54476
- Marshfield Medical Center - Weston
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
Inclusion Criteria:
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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.
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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
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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.
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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.
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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
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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
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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
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
|
Expérimental: 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
Autres noms:
Given IV
Autres noms:
Given PO
Autres noms:
Undergo blood sample collection
Autres noms:
Given IV
Autres noms:
Given IV
Autres noms:
Ancillary studies Undergo ECHO
Autres noms:
Undergo MUGA
Autres noms:
Undergo PET-CT
Autres noms:
Given SC
Autres noms:
Undergo PET-CT
Autres noms:
Given PO
Autres noms:
|
|
Comparateur actif: 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
Autres noms:
Given IV
Autres noms:
Given PO
Autres noms:
Undergo blood sample collection
Autres noms:
Given IV
Autres noms:
Given IV
Autres noms:
Ancillary studies Undergo ECHO
Autres noms:
Undergo MUGA
Autres noms:
Undergo PET-CT
Autres noms:
Given SC
Autres noms:
Undergo PET-CT
Autres noms:
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
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)
Délai: 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)
Délai: 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)
Délai: 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
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Metabolic complete response (CR)
Délai: 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
Délai: 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)
Délai: 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
|
Autres mesures de résultats
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Changes in function (Integrated Correlative Geriatric Assessments Substudy)
Délai: 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)
Délai: 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)
Délai: 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
|
Collaborateurs et enquêteurs
Parrainer
Les enquêteurs
- Chercheur principal: Elizabeth A Brem, SWOG Cancer Research Network
Publications et liens utiles
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
Achèvement primaire (Estimé)
Achèvement de l'étude (Estimé)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
- Tumeurs
- Maladies du système immunitaire
- Tumeurs par type histologique
- Maladies lymphatiques
- Troubles lymphoprolifératifs
- Troubles immunoprolifératifs
- Lymphome non hodgkinien
- Lymphome à cellules B
- Lymphome
- Maladies hémiques et lymphatiques
- Lymphome diffus à grandes cellules B
- Lymphome, cellule B, zone marginale
- Acides aminés, peptides et protéines
- Protéines
- Produits chimiques organiques
- Composés hétérocycliques, 1 anneau
- Composés hétérocycliques
- Composés hétérocycliques, 2 anneaux
- Composés hétérocycliques, anneau fusionné
- Techniques d'investigation
- Techniques de laboratoire clinique
- Techniques et procédures de diagnostic
- Diagnostic
- Acides nucléiques, nucléotides et nucléosides
- Hydrocarbures
- Hydrocarbures, cyclique
- Glucides
- Alcaloïdes
- Hydrocarbures aromatiques polycycliques
- Hydrocarbures, aromatique
- Composés polycycliques
- Glycosides
- Hydrolases glycosides
- Hydrolases
- Enzymes
- Enzymes et coenzymes
- Polysaccharides-lyases
- Lyases en carbone-oxygène
- Lyases
- Indoles
- Anticorps, monoclonal
- Anticorps
- Immunoglobulines
- Immunoprotéines
- Protéines sanguines
- Globulines sériques
- Globulines
- Cytidine
- Nucléosides pyrimidine
- Pyrimidines
- Prégnades
- Grossesse
- Stéroïdes
- Composés à anneau fusionné
- Techniques de chimie, analytique
- Analyse du spectre
- Moutards phosphoramides
- Composés de moutarde d'azote
- Composés moutarde
- Hydrocarbures, halogénés
- Phosphoramides
- Composés organophosphores
- Composés Aza
- Nucléosides
- Ribonucléosides
- Grossissements
- Alcaloïdes Vinca
- Alcaloïdes de la secologane tryptamine
- Alcaloïdes indole
- Indolizidines
- Indolizines
- Anthracyclines
- Naphtacènes
- Aminoglycosides
- Anticorps, monoclonal et murin
- Daunorubicine
- Rituximab
- Prednisone
- Cyclophosphamide
- Azacitidine
- Doxorubicine
- Vincristine
- Hyaluronoglucosaminidase
- Manipulation des échantillons
- Spectroscopie de résonance magnétique
- CC-486
- Ct-p10
- deltacortene
- prednylidene
Autres numéros d'identification d'étude
- NCI-2020-01256
- U10CA180888 (Subvention/contrat des NIH des États-Unis)
- NCI-2020-01256 (Identificateur de registre: CTRP (Clinical Trial Reporting Program))
- S1918 (Autre identifiant: CTEP)
- S1918 (Autre identifiant: SWOG)
Plan pour les données individuelles des participants (IPD)
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Description du régime IPD
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Informations sur les médicaments et les dispositifs, documents d'étude
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