Testing CC-486 (Oral Azacitidine) Plus the Standard Drug Therapy in Patients 75 Years or Older With Newly Diagnosed Diffuse Large B Cell Lymphoma
A Phase II/III Randomized Study of R-MiniCHOP With or Without CC-486 (Oral Azacitidine) in Participants Age 75 Years or Older With Newly Diagnosed Diffuse Large B Cell Lymphoma, Grade IIIB Follicular Lymphoma, Transformed Lymphoma, and High-Grade B-Cell Lymphomas With MYC AND BCL2 and/or BCL6 Rearrangements
3 other identifiers
interventional
422
1 country
176
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started May 2021
Longer than P75 for phase_2
176 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 13, 2021
CompletedFirst Posted
Study publicly available on registry
March 16, 2021
CompletedStudy Start
First participant enrolled
May 20, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
March 1, 2027
May 4, 2026
April 1, 2026
5.8 years
March 13, 2021
May 1, 2026
Conditions
Outcome Measures
Primary Outcomes (3)
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)
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)
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)
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
Secondary Outcomes (3)
Metabolic complete response (CR)
Up to end of cycle 6 or end of treatment
Incidence of adverse events
Until disease progression, assessed up to 5 years
Overall survival (Phase III)
From date of registration to date of death due to any cause, assessed up to 5 years
Other Outcomes (3)
Changes in function (Integrated Correlative Geriatric Assessments Substudy)
From time of randomization up to 24 months after date of registration
Frailty status (fit/unfit vs frail) (Integrated Correlative Geriatric Assessments Substudy)
Baseline
Frailty status (Integrated Correlative Geriatric Assessments Substudy)
Up to 24 months after date of registration
Study Arms (2)
Arm I (oral azacitidine, R-miniCHOP)
EXPERIMENTALPatients 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.
Arm II (R-miniCHOP)
ACTIVE COMPARATORPatients 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.
Interventions
Undergo PET-CT
Given SC
Undergo blood sample collection
Given IV
Given PO
Given IV
Undergo ECHO
Undergo MUGA
Given PO
Undergo PET-CT
Ancillary studies
Given IV
Given IV
Eligibility Criteria
You may qualify if:
- 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.
- +30 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (176)
Banner University Medical Center - Tucson
Tucson, Arizona, 85719, United States
University of Arizona Cancer Center-North Campus
Tucson, Arizona, 85719, United States
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205, United States
Kaiser Permanente-Anaheim
Anaheim, California, 92806, United States
Kaiser Permanente-Baldwin Park
Baldwin Park, California, 91706, United States
Kaiser Permanente-Bellflower
Bellflower, California, 90706, United States
Tower Cancer Research Foundation
Beverly Hills, California, 90211, United States
UC Irvine Health Cancer Center-Newport
Costa Mesa, California, 92627, United States
City of Hope Comprehensive Cancer Center
Duarte, California, 91010, United States
Kaiser Permanente-Fontana
Fontana, California, 92335, United States
Kaiser Permanente South Bay
Harbor City, California, 90710, United States
City of Hope Seacliff
Huntington Beach, California, 92648, United States
City of Hope at Irvine Lennar
Irvine, California, 92618, United States
Kaiser Permanente-Irvine
Irvine, California, 92618, United States
City of Hope Antelope Valley
Lancaster, California, 93534, United States
City of Hope at Long Beach Elm
Long Beach, California, 90813, United States
Tibor Rubin VA Medical Center
Long Beach, California, 90822, United States
Kaiser Permanente Los Angeles Medical Center
Los Angeles, California, 90027, United States
Kaiser Permanente West Los Angeles
Los Angeles, California, 90034, United States
Cedars-Sinai Medical Center
Los Angeles, California, 90048, United States
City of Hope Newport Beach
Newport Beach, California, 92660, United States
Kaiser Permanente-Ontario
Ontario, California, 91761, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, 92868, United States
Stanford Cancer Institute Palo Alto
Palo Alto, California, 94304, United States
Kaiser Permanente - Panorama City
Panorama City, California, 91402, United States
Kaiser Permanente-Riverside
Riverside, California, 92505, United States
Kaiser Permanente-San Diego Zion
San Diego, California, 92120, United States
Kaiser Permanente-San Marcos
San Marcos, California, 92078, United States
UCSF Cancer Center - San Mateo
San Mateo, California, 94402, United States
City of Hope South Pasadena
South Pasadena, California, 91030, United States
City of Hope South Bay
Torrance, California, 90503, United States
City of Hope Upland
Upland, California, 91786, United States
Kaiser Permanente-Woodland Hills
Woodland Hills, California, 91367, United States
Lutheran Hospital - Cancer Centers of Colorado
Golden, Colorado, 80401, United States
Delaware Clinical and Laboratory Physicians PA
Newark, Delaware, 19713, United States
Helen F Graham Cancer Center
Newark, Delaware, 19713, United States
Medical Oncology Hematology Consultants PA
Newark, Delaware, 19713, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136, United States
Emory University Hospital Midtown
Atlanta, Georgia, 30308, United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322, United States
Emory Saint Joseph's Hospital
Atlanta, Georgia, 30342, United States
Augusta University Medical Center
Augusta, Georgia, 30912, United States
Hawaii Cancer Care Inc - Waterfront Plaza
Honolulu, Hawaii, 96813, United States
Queen's Cancer Cenrer - POB I
Honolulu, Hawaii, 96813, United States
Queen's Medical Center
Honolulu, Hawaii, 96813, United States
Straub Clinic and Hospital
Honolulu, Hawaii, 96813, United States
Queen's Cancer Center - Kuakini
Honolulu, Hawaii, 96817, United States
Hawaii Cancer Care - Westridge
‘Aiea, Hawaii, 96701, United States
Pali Momi Medical Center
‘Aiea, Hawaii, 96701, United States
Centralia Oncology Clinic
Centralia, Illinois, 62801, United States
Northwestern University
Chicago, Illinois, 60611, United States
University of Illinois
Chicago, Illinois, 60612, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637, United States
Carle at The Riverfront
Danville, Illinois, 61832, United States
Cancer Care Specialists of Illinois - Decatur
Decatur, Illinois, 62526, United States
Decatur Memorial Hospital
Decatur, Illinois, 62526, United States
Northwestern Medicine Cancer Center Kishwaukee
DeKalb, Illinois, 60115, United States
Carle Physician Group-Effingham
Effingham, Illinois, 62401, United States
Crossroads Cancer Center
Effingham, Illinois, 62401, United States
NorthShore University HealthSystem-Evanston Hospital
Evanston, Illinois, 60201, United States
Northwestern Medicine Cancer Center Delnor
Geneva, Illinois, 60134, United States
NorthShore University HealthSystem-Glenbrook Hospital
Glenview, Illinois, 60026, United States
Northwestern Medicine Glenview Outpatient Center
Glenview, Illinois, 60026, United States
Northwestern Medicine Grayslake Outpatient Center
Grayslake, Illinois, 60030, United States
NorthShore University HealthSystem-Highland Park Hospital
Highland Park, Illinois, 60035, United States
Northwestern Medicine Lake Forest Hospital
Lake Forest, Illinois, 60045, United States
Carle Physician Group-Mattoon/Charleston
Mattoon, Illinois, 61938, United States
UC Comprehensive Cancer Center at Silver Cross
New Lenox, Illinois, 60451, United States
Cancer Care Center of O'Fallon
O'Fallon, Illinois, 62269, United States
Northwestern Medicine Orland Park
Orland Park, Illinois, 60462, United States
University of Chicago Medicine-Orland Park
Orland Park, Illinois, 60462, United States
Illinois CancerCare-Peoria
Peoria, Illinois, 61615, United States
Memorial Hospital East
Shiloh, Illinois, 62269, United States
Carle Cancer Center
Urbana, Illinois, 61801, United States
Northwestern Medicine Cancer Center Warrenville
Warrenville, Illinois, 60555, United States
McFarland Clinic - Ames
Ames, Iowa, 50010, United States
UI Health Care Mission Cancer and Blood - Ankeny Clinic
Ankeny, Iowa, 50023, United States
UI Health Care Mission Cancer and Blood - West Des Moines Clinic
Clive, Iowa, 50325, United States
Iowa Methodist Medical Center
Des Moines, Iowa, 50309, United States
UI Health Care Mission Cancer and Blood - Des Moines Clinic
Des Moines, Iowa, 50309, United States
UI Health Care Mission Cancer and Blood - Laurel Clinic
Des Moines, Iowa, 50314, United States
Ochsner LSU Health Monroe Medical Center
Monroe, Louisiana, 71202, United States
LSU Health Sciences Center at Shreveport
Shreveport, Louisiana, 71103, United States
Tufts Medical Center
Boston, Massachusetts, 02111, United States
Trinity Health Saint Joseph Mercy Hospital Ann Arbor
Ann Arbor, Michigan, 48106, United States
Trinity Health IHA Medical Group Hematology Oncology - Brighton
Brighton, Michigan, 48114, United States
Trinity Health Medical Center - Brighton
Brighton, Michigan, 48114, United States
Trinity Health IHA Medical Group Hematology Oncology - Canton
Canton, Michigan, 48188, United States
Trinity Health Medical Center - Canton
Canton, Michigan, 48188, United States
Chelsea Hospital
Chelsea, Michigan, 48118, United States
Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
Chelsea, Michigan, 48118, United States
Hope Cancer Clinic
Livonia, Michigan, 48154, United States
Trinity Health Saint Mary Mercy Livonia Hospital
Livonia, Michigan, 48154, United States
Huron Gastroenterology PC
Ypsilanti, Michigan, 48106, United States
Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
Ypsilanti, Michigan, 48197, United States
Essentia Health - Deer River Clinic
Deer River, Minnesota, 56636, United States
Essentia Health Cancer Center
Duluth, Minnesota, 55805, United States
Essentia Health Hibbing Clinic
Hibbing, Minnesota, 55746, United States
Essentia Health Sandstone
Sandstone, Minnesota, 55072, United States
Essentia Health Virginia Clinic
Virginia, Minnesota, 55792, United States
Baptist Memorial Hospital and Cancer Center-Oxford
Oxford, Mississippi, 38655, United States
Baptist Memorial Hospital and Cancer Center-Desoto
Southhaven, Mississippi, 38671, United States
Saint Francis Medical Center
Cape Girardeau, Missouri, 63703, United States
Saint Luke's Hospital
Chesterfield, Missouri, 63017, United States
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, 63376, United States
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, 63141, United States
Heartland Regional Medical Center
Saint Joseph, Missouri, 64506, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Siteman Cancer Center-South County
St Louis, Missouri, 63129, United States
Siteman Cancer Center at Christian Hospital
St Louis, Missouri, 63136, United States
Cancer Partners of Nebraska
Lincoln, Nebraska, 68516, United States
Memorial Sloan Kettering Basking Ridge
Basking Ridge, New Jersey, 07920, United States
Englewood Hospital and Medical Center
Englewood, New Jersey, 07631, United States
Monmouth Medical Center Southern Campus
Lakewood, New Jersey, 08701, United States
Monmouth Medical Center
Long Branch, New Jersey, 07740, United States
Memorial Sloan Kettering Monmouth
Middletown, New Jersey, 07748, United States
Memorial Sloan Kettering Bergen
Montvale, New Jersey, 07645, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903, United States
Newark Beth Israel Medical Center
Newark, New Jersey, 07112, United States
Community Medical Center
Toms River, New Jersey, 08755, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
Memorial Sloan Kettering Commack
Commack, New York, 11725, United States
Glens Falls Hospital
Glens Falls, New York, 12801, United States
Memorial Sloan Kettering Westchester
Harrison, New York, 10604, United States
NYU Langone Hospital - Long Island
Mineola, New York, 11501, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
NYP/Weill Cornell Medical Center
New York, New York, 10065, United States
Upstate Cancer Center at Oswego
Oswego, New York, 13126, United States
State University of New York Upstate Medical University
Syracuse, New York, 13210, United States
Memorial Sloan Kettering Nassau
Uniondale, New York, 11553, United States
Upstate Cancer Center at Verona
Verona, New York, 13478, United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599, United States
Cleveland Clinic Cancer Center/Fairview Hospital
Cleveland, Ohio, 44111, United States
Cleveland Clinic Foundation
Cleveland, Ohio, 44195, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
Dayton Physician LLC - Englewood
Dayton, Ohio, 45415, United States
Cleveland Clinic Cancer Center Independence
Independence, Ohio, 44131, United States
Greater Dayton Cancer Center
Kettering, Ohio, 45409, United States
Cleveland Clinic Cancer Center Mansfield
Mansfield, Ohio, 44906, United States
Hillcrest Hospital Cancer Center
Mayfield Heights, Ohio, 44124, United States
North Coast Cancer Care
Sandusky, Ohio, 44870, United States
Cleveland Clinic Cancer Center Strongsville
Strongsville, Ohio, 44136, United States
South Pointe Hospital
Warrensville Heights, Ohio, 44122, United States
Cleveland Clinic Wooster Family Health and Surgery Center
Wooster, Ohio, 44691, United States
Cancer Centers of Southwest Oklahoma Research
Lawton, Oklahoma, 73505, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
Providence Saint Vincent Medical Center
Portland, Oregon, 97225, United States
Portland VA Medical Center
Portland, Oregon, 97239, United States
Medical University of South Carolina
Charleston, South Carolina, 29425, United States
Saint Francis Hospital
Greenville, South Carolina, 29601, United States
Saint Francis Cancer Center
Greenville, South Carolina, 29607, United States
Baptist Memorial Hospital and Cancer Center-Memphis
Memphis, Tennessee, 38120, United States
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112, United States
George E Wahlen Department of Veterans Affairs Medical Center
Salt Lake City, Utah, 84148, United States
University of Virginia Cancer Center
Charlottesville, Virginia, 22908, United States
Inova Schar Cancer Institute
Fairfax, Virginia, 22031, United States
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, 23298, United States
FHCC Overlake
Bellevue, Washington, 98004, United States
FHCC at EvergreenHealth
Kirkland, Washington, 98034, United States
FHCC at Northwest Hospital
Seattle, Washington, 98133, United States
West Virginia University Charleston Division
Charleston, West Virginia, 25304, United States
Duluth Clinic Ashland
Ashland, Wisconsin, 54806, United States
Marshfield Medical Center-EC Cancer Center
Eau Claire, Wisconsin, 54701, United States
Saint Vincent Hospital Cancer Center Green Bay
Green Bay, Wisconsin, 54301, United States
Saint Vincent Hospital Cancer Center at Saint Mary's
Green Bay, Wisconsin, 54303, United States
Gundersen Lutheran Medical Center
La Crosse, Wisconsin, 54601, United States
Marshfield Medical Center-Marshfield
Marshfield, Wisconsin, 54449, United States
Marshfield Medical Center - Minocqua
Minocqua, Wisconsin, 54548, United States
Saint Vincent Hospital Cancer Center at Oconto Falls
Oconto Falls, Wisconsin, 54154, United States
Marshfield Medical Center-Rice Lake
Rice Lake, Wisconsin, 54868, United States
Saint Vincent Hospital Cancer Center at Sheboygan
Sheboygan, Wisconsin, 53081, United States
Marshfield Medical Center-River Region at Stevens Point
Stevens Point, Wisconsin, 54482, United States
Saint Vincent Hospital Cancer Center at Sturgeon Bay
Sturgeon Bay, Wisconsin, 54235-1495, United States
Marshfield Medical Center - Weston
Weston, Wisconsin, 54476, United States
Related Publications (1)
Brem EA, Li H, Beaven AW, Caimi PF, Cerchietti L, Alizadeh AA, Olin R, Henry NL, Dillon H, Little RF, Laubach C, LeBlanc M, Friedberg JW, Smith SM. SWOG 1918: A phase II/III randomized study of R-miniCHOP with or without oral azacitidine (CC-486) in participants age 75 years or older with newly diagnosed aggressive non-Hodgkin lymphomas - Aiming to improve therapy, outcomes, and validate a prospective frailty tool. J Geriatr Oncol. 2022 Mar;13(2):258-264. doi: 10.1016/j.jgo.2021.10.003. Epub 2021 Oct 20.
PMID: 34686472DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Elizabeth A Brem
SWOG Cancer Research Network
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 13, 2021
First Posted
March 16, 2021
Study Start
May 20, 2021
Primary Completion (Estimated)
March 1, 2027
Study Completion (Estimated)
March 1, 2027
Last Updated
May 4, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
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