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

Who is this study for? Adult patients over age 75 with diffuse large B-cell lymphoma
What treatments are being studied? Oral Azacitidine
Status: Suspended
Location: See all (111) locations...
Intervention Type: Drug, Biological, Other
Study Type: Interventional
Study Phase: Phase 2/Phase 3
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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 75
Healthy Volunteers: No
View:

• 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. Positron emission tomography (PET)-computed tomography (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. 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 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

• Hemoglobin (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)

Locations
United States
Arkansas
University of Arkansas for Medical Sciences
Little Rock
Arizona
Banner University Medical Center - Tucson
Tucson
University of Arizona Cancer Center-North Campus
Tucson
California
Kaiser Permanente-Anaheim
Anaheim
Kaiser Permanente-Baldwin Park
Baldwin Park
Kaiser Permanente-Bellflower
Bellflower
Tower Cancer Research Foundation
Beverly Hills
UC Irvine Health Cancer Center-Newport
Costa Mesa
City of Hope Comprehensive Cancer Center
Duarte
Kaiser Permanente-Fontana
Fontana
Kaiser Permanente - Harbor City
Harbor City
City of Hope at Irvine Lennar
Irvine
Kaiser Permanente-Irvine
Irvine
Cedars Sinai Medical Center
Los Angeles
Kaiser Permanente Los Angeles Medical Center
Los Angeles
Kaiser Permanente West Los Angeles
Los Angeles
Kaiser Permanente-Ontario
Ontario
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange
Stanford Cancer Institute Palo Alto
Palo Alto
Kaiser Permanente - Panorama City
Panorama City
Kaiser Permanente-Riverside
Riverside
Kaiser Permanente-San Diego Zion
San Diego
Kaiser Permanente-San Marcos
San Marcos
UCSF Cancer Center - San Mateo
San Mateo
Kaiser Permanente-Woodland Hills
Woodland Hills
Delaware
Delaware Clinical and Laboratory Physicians PA
Newark
Helen F Graham Cancer Center
Newark
Medical Oncology Hematology Consultants PA
Newark
Florida
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami
Georgia
Emory Saint Joseph's Hospital
Atlanta
Emory University Hospital/Winship Cancer Institute
Atlanta
Augusta University Medical Center
Augusta
Hawaii
Hawaii Cancer Care - Savio
'aiea
Pali Momi Medical Center
'aiea
Hawaii Cancer Care Inc - Waterfront Plaza
Honolulu
Queen's Cancer Cenrer - POB I
Honolulu
Queen's Cancer Center - Kuakini
Honolulu
Queen's Medical Center
Honolulu
Straub Clinic and Hospital
Honolulu
Iowa
McFarland Clinic PC - Ames
Ames
Iowa Methodist Medical Center
Des Moines
Medical Oncology and Hematology Associates-Des Moines
Des Moines
Illinois
University of Chicago Comprehensive Cancer Center
Chicago
NorthShore University HealthSystem-Evanston Hospital
Evanston
NorthShore University HealthSystem-Glenbrook Hospital
Glenview
NorthShore University HealthSystem-Highland Park Hospital
Highland Park
UC Comprehensive Cancer Center at Silver Cross
New Lenox
University of Chicago Medicine-Orland Park
Orland Park
Carle Cancer Center
Urbana
Louisiana
LSU Health Sciences Center at Shreveport
Shreveport
Massachusetts
Tufts Medical Center
Boston
Michigan
Saint Joseph Mercy Hospital
Ann Arbor
Saint Joseph Mercy Brighton
Brighton
Trinity Health IHA Medical Group Hematology Oncology - Brighton
Brighton
Saint Joseph Mercy Canton
Canton
Trinity Health IHA Medical Group Hematology Oncology - Canton
Canton
Saint Joseph Mercy Chelsea
Chelsea
Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
Chelsea
Hope Cancer Clinic
Livonia
Trinity Health Saint Mary Mercy Livonia Hospital
Livonia
Huron Gastroenterology PC
Ypsilanti
Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
Ypsilanti
Minnesota
Essentia Health - Deer River Clinic
Deer River
Essentia Health Cancer Center
Duluth
Essentia Health Hibbing Clinic
Hibbing
Essentia Health Sandstone
Sandstone
Essentia Health Virginia Clinic
Virginia
Missouri
Saint Luke's Hospital
Chesterfield
Siteman Cancer Center at West County Hospital
Creve Coeur
Siteman Cancer Center at Christian Hospital
Saint Louis
Siteman Cancer Center-South County
Saint Louis
Washington University School of Medicine
Saint Louis
Siteman Cancer Center at Saint Peters Hospital
Saint Peters
Nebraska
Cancer Partners of Nebraska - Pine Lake
Lincoln
Southeast Nebraska Cancer Center - 68th Street Place
Lincoln
New Jersey
Memorial Sloan Kettering Basking Ridge
Basking Ridge
Englewood Hospital and Medical Center
Englewood
Monmouth Medical Center Southern Campus
Lakewood
Monmouth Medical Center
Long Branch
Memorial Sloan Kettering Monmouth
Middletown
Memorial Sloan Kettering Bergen
Montvale
Rutgers Cancer Institute of New Jersey
New Brunswick
Newark Beth Israel Medical Center
Newark
Community Medical Center
Toms River
New York
Roswell Park Cancer Institute
Buffalo
Memorial Sloan Kettering Commack
Commack
Glens Falls Hospital
Glens Falls
Memorial Sloan Kettering Westchester
Harrison
NYU Winthrop Hospital
Mineola
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York
Memorial Sloan Kettering Cancer Center
New York
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York
NYP/Weill Cornell Medical Center
New York
Upstate Cancer Center at Oneida
Oneida
Upstate Cancer Center at Oswego
Oswego
State University of New York Upstate Medical University
Syracuse
Memorial Sloan Kettering Nassau
Uniondale
Ohio
Ohio State University Comprehensive Cancer Center
Columbus
Oklahoma
Cancer Centers of Southwest Oklahoma Research
Lawton
University of Oklahoma Health Sciences Center
Oklahoma City
South Carolina
Medical University of South Carolina
Charleston
Saint Francis Cancer Center
Greenville
Utah
Huntsman Cancer Institute/University of Utah
Salt Lake City
Virginia
University of Virginia Cancer Center
Charlottesville
Washington
FHCC Overlake
Bellevue
Seattle Cancer Care Alliance at EvergreenHealth
Kirkland
FHCC at Northwest Hospital
Seattle
Wisconsin
Duluth Clinic Ashland
Ashland
Gundersen Lutheran Medical Center
La Crosse
Marshfield Medical Center-Marshfield
Marshfield
West Virginia
West Virginia University Charleston Division
Charleston
Time Frame
Start Date: March 19, 2021
Completion Date: March 31, 2025
Participants
Target number of participants: 422
Treatments
Experimental: 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 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.
Active Comparator: Arm II (R-miniCHOP)
Patients receive rituximab IV (or 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.
Sponsors
Leads: National Cancer Institute (NCI)

This content was sourced from clinicaltrials.gov

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