A Randomized Phase 3 Trial of Nivolumab (NSC# 748726) in Combination With Chemo-Immunotherapy for the Treatment of Newly Diagnosed Primary Mediastinal B-Cell Lymphoma

Who is this study for? Patients with Large B-Cell Lymphoma
What treatments are being studied? Doxorubicin Hydrochloride+Etoposide Phosphate+Filgrastim+Prednisone
Status: Recruiting
Location: See all (186) locations...
Intervention Type: Procedure, Drug, Biological, Radiation
Study Type: Interventional
Study Phase: Phase 3
SUMMARY

This phase III trial compares the effects of nivolumab with chemo-immunotherapy versus chemo-immunotherapy alone in treating patients with newly diagnosed primary mediastinal B-cell lymphoma (PMBCL). Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of cancer cells to grow and spread. Treatment for PMBCL involves chemotherapy combined with an immunotherapy called rituximab. Chemotherapy drugs 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. Rituximab is a monoclonal antibody. It binds to a protein called CD20, which is found on B cells (a type of white blood cell) and some types of cancer cells. This may help the immune system kill cancer cells. Giving nivolumab with chemo-immunotherapy may help treat patients with PMBCL.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 2
Healthy Volunteers: No
View:

• Age >= 2 years

• Patient must have histologically confirmed primary mediastinal B-cell lymphoma (PMBCL) as defined by World Health Organization (WHO) criteria

• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 or ECOG performance status of 3 if poor performance is related to lymphoma

• Children's Oncology Group (COG) Institutions: Use Karnofsky for patients >= 17 and < 18 years of age and Lansky for patients < 17 years of age

• Adults (age 18 or older): Creatinine clearance >= 30 mL/min, as estimated by the Cockcroft and Gault formula. The creatinine value used in the calculation must have been obtained within 28 days prior to registration. Estimated creatinine clearance is based on actual body weight

• Pediatric Patients (age < 18 years): The following must have been obtained within 14 days prior to registration:

• Measured or calculated (based on institutional standard) creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2, or

• Serum creatinine =< 1.5 x institutional upper limit of normal (IULN), or a serum creatinine based on age/gender as follows:

• Age : 2 to < 6 year; Maximum serum creatinine (mg/dL): 0.8 (male; 0.8 (female)

• Age : 6 to < 10 years; Maximum serum creatinine (mg/dL): 1 (male); 1 (female)

• Age : >= 16 years to < 18 years; Maximum serum creatinine (mg/dL): 1.7 (male); 1.4 (female)

• Patients with abnormal liver function will be eligible to enroll if the lab abnormality is thought to be due to the lymphoma or Gilbert's syndrome

• Age >= 18 years: Ejection fraction of >= 50% by echocardiogram

• Age < 18 years: Shortening fraction of >= 27% by echocardiogram, or ejection fraction of >= 50% by radionuclide angiogram

• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial

• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated

• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load

• All patients and/or their parents or legal guardians must sign a written informed consent

• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Locations
United States
Alaska
Providence Alaska Medical Center
Recruiting
Anchorage
Alabama
Children's Hospital of Alabama
Recruiting
Birmingham
USA Health Strada Patient Care Center
Recruiting
Mobile
Arkansas
Arkansas Children's Hospital
Recruiting
Little Rock
Arizona
Banner Children's at Desert
Recruiting
Mesa
Banner University Medical Center - Tucson
Suspended
Tucson
California
City of Hope Comprehensive Cancer Center
Recruiting
Duarte
Loma Linda University Medical Center
Recruiting
Loma Linda
Children's Hospital Los Angeles
Recruiting
Los Angeles
Mattel Children's Hospital UCLA
Suspended
Los Angeles
Valley Children's Hospital
Recruiting
Madera
Kaiser Permanente-Oakland
Recruiting
Oakland
Children's Hospital of Orange County
Recruiting
Orange
UC Irvine Health/Chao Family Comprehensive Cancer Center
Recruiting
Orange
Lucile Packard Children's Hospital Stanford University
Recruiting
Palo Alto
University of California Davis Comprehensive Cancer Center
Recruiting
Sacramento
Rady Children's Hospital - San Diego
Recruiting
San Diego
Colorado
Children's Hospital Colorado
Recruiting
Aurora
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
Recruiting
Denver
Connecticut
Connecticut Children's Medical Center
Recruiting
Hartford
Washington, D.c.
Children's National Medical Center
Recruiting
Washington
MedStar Georgetown University Hospital
Recruiting
Washington
Delaware
Alfred I duPont Hospital for Children
Recruiting
Wilmington
Florida
Broward Health Medical Center
Recruiting
Fort Lauderdale
University of Florida Health Science Center - Gainesville
Recruiting
Gainesville
Memorial Regional Hospital/Joe DiMaggio Children's Hospital
Recruiting
Hollywood
Nemours Children's Clinic-Jacksonville
Recruiting
Jacksonville
Arnold Palmer Hospital for Children
Recruiting
Orlando
Nemours Children's Hospital
Recruiting
Orlando
Saint Joseph's Hospital/Children's Hospital-Tampa
Recruiting
Tampa
Georgia
Children's Healthcare of Atlanta - Egleston
Not yet recruiting
Atlanta
Emory Proton Therapy Center
Recruiting
Atlanta
Emory Saint Joseph's Hospital
Recruiting
Atlanta
Emory University Hospital Midtown
Recruiting
Atlanta
Emory University Hospital/Winship Cancer Institute
Recruiting
Atlanta
Memorial Health University Medical Center
Recruiting
Savannah
Hawaii
Kapiolani Medical Center for Women and Children
Recruiting
Honolulu
Iowa
University of Iowa/Holden Comprehensive Cancer Center
Recruiting
Iowa City
Idaho
Saint Luke's Cancer Institute - Boise
Recruiting
Boise
Illinois
Rush - Copley Medical Center
Recruiting
Aurora
Lurie Children's Hospital-Chicago
Recruiting
Chicago
Northwestern University
Recruiting
Chicago
University of Chicago Comprehensive Cancer Center
Recruiting
Chicago
University of Illinois
Recruiting
Chicago
Carle on Vermilion
Recruiting
Danville
Decatur Memorial Hospital
Recruiting
Decatur
Northwestern Medicine Cancer Center Kishwaukee
Recruiting
Dekalb
Carle Physician Group-Effingham
Recruiting
Effingham
Northwestern Medicine Cancer Center Delnor
Recruiting
Geneva
Northwestern Medicine Lake Forest Hospital
Recruiting
Lake Forest
Carle Physician Group-Mattoon/Charleston
Recruiting
Mattoon
Loyola University Medical Center
Recruiting
Maywood
Advocate Children's Hospital-Oak Lawn
Recruiting
Oak Lawn
Advocate Children's Hospital-Park Ridge
Recruiting
Park Ridge
Saint Jude Midwest Affiliate
Recruiting
Peoria
Southern Illinois University School of Medicine
Recruiting
Springfield
Carle Cancer Center
Recruiting
Urbana
Northwestern Medicine Cancer Center Warrenville
Recruiting
Warrenville
Indiana
Riley Hospital for Children
Recruiting
Indianapolis
Kentucky
University of Kentucky/Markey Cancer Center
Recruiting
Lexington
Norton Children's Hospital
Recruiting
Louisville
Louisiana
Ochsner Medical Center Jefferson
Recruiting
New Orleans
Massachusetts
Dana-Farber Cancer Institute
Recruiting
Boston
Tufts Medical Center
Recruiting
Boston
Maryland
Johns Hopkins University/Sidney Kimmel Cancer Center
Recruiting
Baltimore
Sinai Hospital of Baltimore
Recruiting
Baltimore
Maine
Eastern Maine Medical Center
Suspended
Bangor
Maine Children's Cancer Program
Recruiting
Scarborough
Michigan
C S Mott Children's Hospital
Recruiting
Ann Arbor
Michigan State University Clinical Center
Recruiting
East Lansing
Helen DeVos Children's Hospital at Spectrum Health
Recruiting
Grand Rapids
Beaumont Children's Hospital-Royal Oak
Recruiting
Royal Oak
Minnesota
Fairview Southdale Hospital
Recruiting
Edina
Unity Hospital
Recruiting
Fridley
Abbott-Northwestern Hospital
Recruiting
Minneapolis
Children's Hospitals and Clinics of Minnesota - Minneapolis
Recruiting
Minneapolis
Park Nicollet Clinic - Saint Louis Park
Recruiting
Saint Louis Park
United Hospital
Recruiting
Saint Paul
Missouri
Siteman Cancer Center at West County Hospital
Recruiting
Creve Coeur
Children's Mercy Hospitals and Clinics
Recruiting
Kansas City
Mercy Hospital Saint Louis
Recruiting
Saint Louis
Siteman Cancer Center-South County
Recruiting
Saint Louis
Washington University School of Medicine
Recruiting
Saint Louis
Siteman Cancer Center at Saint Peters Hospital
Recruiting
Saint Peters
Mississippi
University of Mississippi Medical Center
Recruiting
Jackson
North Carolina
AdventHealth Infusion Center Asheville
Recruiting
Asheville
Mission Hospital
Recruiting
Asheville
Carolinas Medical Center/Levine Cancer Institute
Recruiting
Charlotte
East Carolina University
Recruiting
Greenville
AdventHealth Hendersonville
Recruiting
Hendersonville
Wake Forest University Health Sciences
Recruiting
Winston-salem
North Dakota
Sanford Broadway Medical Center
Recruiting
Fargo
Nebraska
Children's Hospital and Medical Center of Omaha
Recruiting
Omaha
University of Nebraska Medical Center
Recruiting
Omaha
New Hampshire
Dartmouth Hitchcock Medical Center
Recruiting
Lebanon
New Jersey
Memorial Sloan Kettering Basking Ridge
Recruiting
Basking Ridge
Hackensack University Medical Center
Recruiting
Hackensack
Memorial Sloan Kettering Monmouth
Recruiting
Middletown
Memorial Sloan Kettering Bergen
Recruiting
Montvale
Morristown Medical Center
Recruiting
Morristown
Rutgers Cancer Institute of New Jersey
Recruiting
New Brunswick
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
Suspended
New Brunswick
Saint Joseph's Regional Medical Center
Recruiting
Paterson
Nevada
Alliance for Childhood Diseases/Cure 4 the Kids Foundation
Recruiting
Las Vegas
Renown Regional Medical Center
Recruiting
Reno
New York
Albany Medical Center
Recruiting
Albany
Roswell Park Cancer Institute
Recruiting
Buffalo
Memorial Sloan Kettering Commack
Recruiting
Commack
Memorial Sloan Kettering Westchester
Recruiting
Harrison
The Steven and Alexandra Cohen Children's Medical Center of New York
Recruiting
New Hyde Park
Memorial Sloan Kettering Cancer Center
Recruiting
New York
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
Recruiting
New York
NYP/Weill Cornell Medical Center
Recruiting
New York
University of Rochester
Recruiting
Rochester
Stony Brook University Medical Center
Recruiting
Stony Brook
State University of New York Upstate Medical University
Recruiting
Syracuse
Memorial Sloan Kettering Nassau
Recruiting
Uniondale
New York Medical College
Recruiting
Valhalla
Ohio
Children's Hospital Medical Center of Akron
Recruiting
Akron
Cincinnati Children's Hospital Medical Center
Recruiting
Cincinnati
Cleveland Clinic Foundation
Recruiting
Cleveland
Rainbow Babies and Childrens Hospital
Recruiting
Cleveland
Nationwide Children's Hospital
Recruiting
Columbus
Dayton Children's Hospital
Recruiting
Dayton
ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
Recruiting
Toledo
Oklahoma
University of Oklahoma Health Sciences Center
Recruiting
Oklahoma City
Oregon
Oregon Health and Science University
Recruiting
Portland
Pennsylvania
Lehigh Valley Hospital-Cedar Crest
Recruiting
Allentown
Geisinger Medical Center
Recruiting
Danville
Penn State Children's Hospital
Recruiting
Hershey
Children's Hospital of Philadelphia
Recruiting
Philadelphia
Saint Christopher's Hospital for Children
Recruiting
Philadelphia
Children's Hospital of Pittsburgh of UPMC
Recruiting
Pittsburgh
Rhode Island
Rhode Island Hospital
Recruiting
Providence
South Carolina
Prisma Health Richland Hospital
Recruiting
Columbia
BI-LO Charities Children's Cancer Center
Recruiting
Greenville
Prisma Health Cancer Institute - Eastside
Recruiting
Greenville
Saint Francis Cancer Center
Recruiting
Greenville
Saint Francis Hospital
Recruiting
Greenville
South Dakota
Sanford USD Medical Center - Sioux Falls
Recruiting
Sioux Falls
Tennessee
East Tennessee Childrens Hospital
Recruiting
Knoxville
Saint Jude Children's Research Hospital
Recruiting
Memphis
The Children's Hospital at TriStar Centennial
Recruiting
Nashville
Vanderbilt University/Ingram Cancer Center
Recruiting
Nashville
Texas
Texas Tech University Health Sciences Center-Amarillo
Recruiting
Amarillo
Dell Children's Medical Center of Central Texas
Recruiting
Austin
Driscoll Children's Hospital
Recruiting
Corpus Christi
Medical City Dallas Hospital
Recruiting
Dallas
UT Southwestern/Simmons Cancer Center-Dallas
Recruiting
Dallas
El Paso Children's Hospital
Recruiting
El Paso
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Recruiting
Houston
M D Anderson Cancer Center
Recruiting
Houston
Covenant Children's Hospital
Recruiting
Lubbock
UMC Cancer Center / UMC Health System
Recruiting
Lubbock
Children's Hospital of San Antonio
Recruiting
San Antonio
Methodist Children's Hospital of South Texas
Recruiting
San Antonio
University of Texas Health Science Center at San Antonio
Recruiting
San Antonio
Utah
Primary Children's Hospital
Recruiting
Salt Lake City
Virginia
Inova Fairfax Hospital
Recruiting
Falls Church
Children's Hospital of The King's Daughters
Recruiting
Norfolk
Virginia Commonwealth University/Massey Cancer Center
Recruiting
Richmond
Carilion Children's
Recruiting
Roanoke
Washington
Valley Medical Center
Recruiting
Renton
Seattle Children's Hospital
Recruiting
Seattle
Providence Sacred Heart Medical Center and Children's Hospital
Recruiting
Spokane
Madigan Army Medical Center
Recruiting
Tacoma
Mary Bridge Children's Hospital and Health Center
Recruiting
Tacoma
Wisconsin
University of Wisconsin Carbone Cancer Center
Recruiting
Madison
Marshfield Medical Center-Marshfield
Recruiting
Marshfield
West Virginia
West Virginia University Charleston Division
Recruiting
Charleston
Other Locations
Australia
John Hunter Children's Hospital
Suspended
Hunter Regional Mail Centre
Perth Children's Hospital
Suspended
Perth
Queensland Children's Hospital
Suspended
South Brisbane
The Children's Hospital at Westmead
Suspended
Westmead
Canada
University of Alberta Hospital
Suspended
Edmonton
IWK Health Centre
Suspended
Halifax
McMaster Children's Hospital at Hamilton Health Sciences
Suspended
Hamilton
Children's Hospital
Suspended
London
Centre Hospitalier Universitaire Sainte-Justine
Suspended
Montreal
The Montreal Children's Hospital of the MUHC
Suspended
Montreal
Children's Hospital of Eastern Ontario
Suspended
Ottawa
Centre Hospitalier Universitaire de Quebec
Suspended
Quebec
Janeway Child Health Centre
Suspended
Saint John's
Hospital for Sick Children
Suspended
Toronto
CancerCare Manitoba
Suspended
Winnipeg
Puerto Rico
HIMA San Pablo Oncologic Hospital
Recruiting
Caguas
Time Frame
Start Date: June 7, 2021
Estimated Completion Date: December 31, 2028
Participants
Target number of participants: 192
Treatments
Active Comparator: Arm A (DA-EPOCH-R)
Patients receive prednisone or prednisolone PO QD on days 1-5 and rituximab IV or rituximab and hyaluronidase human SC over 5 minutes on day 1 or 5. Patients also receive etoposide phosphate, doxorubicin hydrochloride, and vincristine sulfate IV over 96 hours on days 1-4 and cyclophosphamide IV over 30-60 minutes on day 5. Beginning 24-72 hours after completing cyclophosphamide, patients receive filgrastim or pegylated filgrastim SC daily until ANC is >= 500/uL after the expected nadir. Treatment repeats every 21 days for up to 6 cycles (5 if the patient had 1 prior cycle of treatment) in the absence of disease progression or unacceptable toxicity. Patients also undergo FDG-PET/CT on study,
Experimental: Arm B (DA-EPOCH-R, nivolumab)
Patients receive treatment as in Arm A. Patients also receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 6 cycles (5 if the patient had 1 prior cycle of treatment) in the absence of disease progression or unacceptable toxicity. Patients also undergo FDG-PET/CT on study,
Active Comparator: Arm C (R-CHOP)
Patients receive prednisone or prednisolone PO QD on days 1-5 and rituximab IV or rituximab and hyaluronidase human SC over 5 minutes on day 1 or 5. Patients also receive cyclophosphamide IV over 30-60 minutes, doxorubicin hydrochloride IV over 1-15 minutes or up to 60 minutes, and vincristine sulfate IV over 1 or up to 60 minutes on day 1. Treatment repeats every 21 days for up to 6 cycles (5 if the patient had 1 prior cycle of treatment) in the absence of disease progression or unacceptable toxicity. Patients also undergo FDG-PET/CT on study,
Experimental: Arm D (R-CHOP, nivolumab)
Patients receive treatment as in Arm C. Patients also receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 6 cycles (5 if the patient had 1 prior cycle of treatment) in the absence of disease progression or unacceptable toxicity. Patients also undergo FDG-PET/CT on study,
Active Comparator: Arm E (R-CHOP, radiation therapy)
Patients receive treatment as in Arm C. Within 6-8 weeks after completion of chemotherapy, patients undergo radiation therapy over 25 fractions. Patients also undergo FDG-PET/CT on study,
Experimental: Arm F (R-CHOP, nivolumab, radiation therapy)
Patients receive treatment as in Arm D. Within 6-8 weeks after completion of chemotherapy, patients undergo radiation therapy over 25 fractions. Patients also undergo FDG-PET/CT on study,
Authors
Craig Erker, Nader K. El-Mallawany, Hamayun Imran, Elyssa M. Rubin, Robin Y. Dulman, Haydar A. Frangoul, Laurel C. Truscott, Nina S. Kadan-Lottick, Alissa Kahn, Eric C. Larsen, Kathryn L. Laurie, Marcio H. Malogolowkin, Jessica C. Hochberg, Mary L. Schmidt, Matthew J. Ehrhardt, Yun Choi, Eric J. Lowe, William A. May, Nadine P. SantaCruz, Bryan A. Faller, Ashok B. Raj, Emily B. Walling, Jennifer A. Belsky, Keith J. August, Elizabeth A. Brem, Kishor M. Bhende, Howland E. Crosswell, Stanton C. Goldman, Thomas W. McLean, Michael S. Isakoff, Justine M. Kahn, Kayelyn J. Wagner, Mukund G. Dole, David L. Becton, Laura E. Agresta, Rabi Hanna, Erika Friehling, Alex F. Herrera, Timothy C. Griffin, Robin D. Hanson, Jordyn R. Griffin, Erwood G. Edwards, Robin E. Norris, Ranjan Bista, Jennifer A. Domm, Don E. Eslin, William B. Slayton, Iftikhar Hanif, Holly E. Pariury, Mark A. Ranalli, David S. Dickens, Erin K. Barr, Leo Mascarenhas, Erin Wright, Laura E. Hogan, Jamie L. Dargart, Theodore B. Moore, Duncan S. Stearns, Andrew L. Pendleton, Krishna C. Alluri, Lisa G Roth, Craig A. Mullen, Jose M. Esquilin, Aarati V. Rao, Joseph C. Torkildson, Michelle A. Manalang, Clare J. Twist, Craig Lotterman, Aniket Saha, Burton E. Appel, Kimberly J. Davies, Eugenia Chang, Arlene S. Redner, James T. Badgett, Robert G. Irwin, Susan E. Spiller, Mallorie B. Heneghan, Douglas J. Scothorn, Eugene Suh, Judy L. Felgenhauer, Jacob A. Troutman, Ryan J. Summers, Minnie Abromowitch, Kelly W. Maloney, Frederick Lansigan, Wade T. Kyono, Amy A. Smith, Emi H. Caywood, William D. Roberts, Gregory P. Brandt, Christine M. Smith, Lisa M. McGregor, Stacy L. Cooper, Laura A. Campbell, Jennifer J. Welch, Jagadeesh Ramdas, Philip M. Monteleone, Stuart L. Cramer, Laura J. Klesse, Andrea R. Whitfield, Jay Michael S. Balagtas, Joel A. Kaplan, Gregory E. Halligan, Brenda J. Wittman, Robert J. Hayashi, Samuel J. Milanovich, Alan K. Ikeda, Nkechi I. Mba, Laura K. Gowans, Martha M. Pacheco, Rebecca E. McFall, Michael K. Richards, Steven J. Kuerbitz, Joanna L. Weinstein, Lauren R. Weintraub, Kristie A. Blum, Jason M. Fixler, Ana C. Galtarossa Xavier, Jill C. Beck, Jennifer J. Clark, Jennifer L. Heaberlin, Albert Kheradpour, Jeffrey S. Dome, Melissa A. Forouhar, Mohamad H. Badawi, Reem Karmali, David M. King, Jhon A. Guerra, Kenneth B. De Santes, Morag Whyte, Elizabeth L. Hesketh, Karen S. Fernandez, Sarah W. Alexander, Ashley Chopek, Lisa A. Goodyear, Sharon B. Abish, Maria T. Grosse-Perdekamp, Yvan Samson, Anne-Marie R. Langevin, Donna L. Johnston, Shannon M. Cohn, Najat C. Daw, Uma H. Athale, Shayna M. Zelcer, Rene Y. McNall-Knapp, Bhavna Padhye, Anne F. Reilly, Kathleen J. Yost, Jaime M. Libes, Archana Sharma, Samer Zaid Kaylani, Hector M. Rodriguez-Cortes, Amber M. D'Souza, Christopher J. Forlenza, Bill H. Chang, Sarah J. McKillop, Sarah E. Leary, Anderson (Andy) B. Collier, Jennifer L. McNeer
Sponsors
Leads: National Cancer Institute (NCI)

This content was sourced from clinicaltrials.gov

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