AzTrials
AzTrials

Primary Mediastinal Large B-Cell LymphomaPhase 3NCT04759586

Nivolumab in Combination With Chemo-Immunotherapy for the Treatment of Newly Diagnosed Primary Mediastinal B-Cell Lymphoma

A Phase 3 study testing Biospecimen Collection, Bone Marrow Aspiration and Bone Marrow Biopsy in people with Primary Mediastinal Large B-Cell Lymphoma, run by National Cancer Institute (NCI) at 233 sites in 4 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 2 years and older
What is being tested?
Biospecimen Collection, Bone Marrow Aspiration and Bone Marrow Biopsy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
244 participants
Where
233 sitesin 4 countries
Study dates
5 Oct 2021to 30 Jun 2027
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 2 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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:
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  • 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/sex 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 : 10 to < 13 years; Maximum serum creatinine (mg/dL): 1.2 (male); 1.2 (female)
  • Age : 13 to < 16 years; Maximum serum creatinine (mg/dL): 1.5 (male); 1.4 (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

Who cannot join

  • Administration of prior anti-cancer therapy except as outlined below:
  • A short course (=< 2 weeks) of corticosteroids for the relief of lymphoma-related symptoms
  • A single course of COP (cyclophosphamide, vincristine, and prednisone)
  • One cycle of chemo-immunotherapy including R-CHOP, DA-EPOCH-R, a pediatric mature B-cell non-Hodgkin lymphoma (B-NHL) induction therapy (such as ANHL1131), or intrathecal chemotherapy that has not started more than 21 days prior to enrollment
  • Active ischemic heart disease or heart failure
  • Active uncontrolled infection
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  • Central nervous system (CNS) involvement of lymphoma
  • Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with safety or efficacy assessment of this trial
  • Active autoimmune disease that has required systemic treatment (such as disease modifying agents, corticosteroids, or immunosuppressive agents) in the past 2 years. Replacement therapy such as thyroxine, insulin or physiologic corticosteroid for adrenal or pituitary insufficiency is not considered a form of systemic treatment
  • In patients < 18 years of age hepatitis B serologies consistent with past or current infections
  • Patients with severe hepatic impairment (Child-Pugh class C or serum total bilirubin > 5.0 mg/dL) unless thought to be due to lymphoma or Gilbert's syndrome
  • Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential
  • Sexually active patients of reproductive potential who have not agreed to use a highly effective contraceptive method (failure rate of < 1% per year when used consistently and correctly) for the duration of their study participation
  • Lactating females are not eligible unless they have agreed not to breastfeed their infants starting with the first dose of study therapy and for at least 6 months after the last dose of rituximab

Trial locations and contacts

233 sites in 4 countries.

233 sites in 4 countries

United States215 sites

  • Children's Hospital Medical Center of Akron

    Akron, Ohio, 44308

  • Albany Medical Center

    Albany, New York, 12208

  • Presbyterian Hospital

    Albuquerque, New Mexico, 87106

  • Lehigh Valley Hospital-Cedar Crest

    Allentown, Pennsylvania, 18103

  • Texas Tech University Health Sciences Center-Amarillo

    Amarillo, Texas, 79106

  • Providence Alaska Medical Center

    Anchorage, Alaska, 99508

  • UI Health Care Mission Cancer and Blood - Ankeny Clinic

    Ankeny, Iowa, 50023

  • C S Mott Children's Hospital

    Ann Arbor, Michigan, 48109

  • Mission Hospital

    Asheville, North Carolina, 28801

  • AdventHealth Infusion Center Asheville

    Asheville, North Carolina, 28803

  • Emory Proton Therapy Center

    Atlanta, Georgia, 30308

  • Emory University Hospital Midtown

    Atlanta, Georgia, 30308

  • Emory University Hospital/Winship Cancer Institute

    Atlanta, Georgia, 30322

  • Children's Healthcare of Atlanta - Arthur M Blank Hospital

    Atlanta, Georgia, 30329

  • Emory Saint Joseph's Hospital

    Atlanta, Georgia, 30342

  • Children's Hospital Colorado

    Aurora, Colorado, 80045

  • Rush-Copley Medical Center

    Aurora, Illinois, 60504

  • Dell Children's Medical Center of Central Texas

    Austin, Texas, 78723

  • University of Maryland/Greenebaum Cancer Center

    Baltimore, Maryland, 21201

  • Greater Baltimore Medical Center

    Baltimore, Maryland, 21204

  • Sinai Hospital of Baltimore

    Baltimore, Maryland, 21215

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • Eastern Maine Medical Center

    Bangor, Maine, 04401

  • Memorial Sloan Kettering Basking Ridge

    Basking Ridge, New Jersey, 07920

  • Walter Reed National Military Medical Center

    Bethesda, Maryland, 20889-5600

  • Children's Hospital of Alabama

    Birmingham, Alabama, 35233

  • Saint Luke's Cancer Institute - Boise

    Boise, Idaho, 83712

  • Tufts Medical Center

    Boston, Massachusetts, 02111

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • Minnesota Oncology - Burnsville

    Burnsville, Minnesota, 55337

  • Vandalia Health/CAMC Institute for Academic Medicine

    Charleston, West Virginia, 25304

  • Carolinas Medical Center/Levine Cancer Institute

    Charlotte, North Carolina, 28203

  • Novant Health Presbyterian Medical Center

    Charlotte, North Carolina, 28204

  • University of Virginia Cancer Center

    Charlottesville, Virginia, 22908

  • Saint Luke's Hospital

    Chesterfield, Missouri, 63017

  • Lurie Children's Hospital-Chicago

    Chicago, Illinois, 60611

  • Northwestern University

    Chicago, Illinois, 60611

  • University of Illinois

    Chicago, Illinois, 60612

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

  • Siteman Cancer Center at Saint Peters Hospital

    City of Saint Peters, Missouri, 63376

  • Rainbow Babies and Childrens Hospital

    Cleveland, Ohio, 44106

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • UI Health Care Mission Cancer and Blood - West Des Moines Clinic

    Clive, Iowa, 50325

  • Prisma Health Richland Hospital

    Columbia, South Carolina, 29203

  • Nationwide Children's Hospital

    Columbus, Ohio, 43205

  • Memorial Sloan Kettering Commack

    Commack, New York, 11725

  • Mercy Hospital

    Coon Rapids, Minnesota, 55433

  • Driscoll Children's Hospital

    Corpus Christi, Texas, 78411

  • UC Irvine Health Cancer Center-Newport

    Costa Mesa, California, 92627

  • Siteman Cancer Center at West County Hospital

    Creve Coeur, Missouri, 63141

  • Medical City Dallas Hospital

    Dallas, Texas, 75230

  • UT Southwestern/Simmons Cancer Center-Dallas

    Dallas, Texas, 75390

  • Carle at The Riverfront

    Danville, Illinois, 61832

  • Geisinger Medical Center

    Danville, Pennsylvania, 17822

  • Dayton Children's Hospital

    Dayton, Ohio, 45404

  • Dayton Physician LLC - Englewood

    Dayton, Ohio, 45415

  • Decatur Memorial Hospital

    Decatur, Illinois, 62526

  • Northwestern Medicine Cancer Center Kishwaukee

    DeKalb, Illinois, 60115

  • Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center

    Denver, Colorado, 80218

  • Blank Children's Hospital

    Des Moines, Iowa, 50309

  • Mercy Medical Center - Des Moines

    Des Moines, Iowa, 50314

  • UI Health Care Mission Cancer and Blood - Laurel Clinic

    Des Moines, Iowa, 50314

  • Children's Hospital of Michigan

    Detroit, Michigan, 48201

  • Henry Ford Hospital

    Detroit, Michigan, 48202

  • Kaiser Permanente Downey Medical Center

    Downey, California, 90242

  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010

  • Michigan State University

    East Lansing, Michigan, 48823

  • Fairview Southdale Hospital

    Edina, Minnesota, 55435

  • Carle Physician Group-Effingham

    Effingham, Illinois, 62401

  • El Paso Children's Hospital

    El Paso, Texas, 79905

  • Inova Fairfax Hospital

    Falls Church, Virginia, 22042

  • Sanford Broadway Medical Center

    Fargo, North Dakota, 58122

  • Broward Health Medical Center

    Fort Lauderdale, Florida, 33316

  • Golisano Children's Hospital of Southwest Florida

    Fort Myers, Florida, 33908

  • Unity Hospital

    Fridley, Minnesota, 55432

  • UF Health Cancer Institute - Gainesville

    Gainesville, Florida, 32610

  • Northwestern Medicine Cancer Center Delnor

    Geneva, Illinois, 60134

  • Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital

    Grand Rapids, Michigan, 49503

  • East Carolina University

    Greenville, North Carolina, 27834

  • Saint Francis Hospital

    Greenville, South Carolina, 29601

  • BI-LO Charities Children's Cancer Center

    Greenville, South Carolina, 29605

  • Saint Francis Cancer Center

    Greenville, South Carolina, 29607

  • Prisma Health Cancer Institute - Eastside

    Greenville, South Carolina, 29615

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • Memorial Sloan Kettering Westchester

    Harrison, New York, 10604

  • Connecticut Children's Medical Center

    Hartford, Connecticut, 06106

  • AdventHealth Hendersonville

    Hendersonville, North Carolina, 28792

  • Penn State Children's Hospital

    Hershey, Pennsylvania, 17033

  • Memorial Regional Hospital/Joe DiMaggio Children's Hospital

    Hollywood, Florida, 33021

  • Kapiolani Medical Center for Women and Children

    Honolulu, Hawaii, 96826

  • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

    Houston, Texas, 77030

  • Houston Methodist Hospital

    Houston, Texas, 77030

  • UT MD Anderson Cancer Center

    Houston, Texas, 77030

  • Riley Hospital for Children

    Indianapolis, Indiana, 46202

  • University of Iowa/Holden Comprehensive Cancer Center

    Iowa City, Iowa, 52242

  • UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care

    Irvine, California, 92612

  • City of Hope at Irvine Lennar

    Irvine, California, 92618

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216

  • Nemours Children's Clinic-Jacksonville

    Jacksonville, Florida, 32207

  • Bronson Methodist Hospital

    Kalamazoo, Michigan, 49007

  • Children's Mercy Hospitals and Clinics

    Kansas City, Missouri, 64108

  • Greater Dayton Cancer Center

    Kettering, Ohio, 45409

  • Kettering Medical Center

    Kettering, Ohio, 45429

  • East Tennessee Childrens Hospital

    Knoxville, Tennessee, 37916

  • Northwestern Medicine Lake Forest Hospital

    Lake Forest, Illinois, 60045

  • Alliance for Childhood Diseases/Cure 4 the Kids Foundation

    Las Vegas, Nevada, 89135

  • Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center

    Lebanon, New Hampshire, 03756

  • University of Kentucky/Markey Cancer Center

    Lexington, Kentucky, 40536

  • Arkansas Children's Hospital

    Little Rock, Arkansas, 72202-3591

  • Loma Linda University Medical Center

    Loma Linda, California, 92354

  • Miller Children's and Women's Hospital Long Beach

    Long Beach, California, 90806

  • Children's Hospital Los Angeles

    Los Angeles, California, 90027

  • Cedars-Sinai Medical Center

    Los Angeles, California, 90048

  • Mattel Children's Hospital UCLA

    Los Angeles, California, 90095

  • Norton Children's Hospital

    Louisville, Kentucky, 40202

  • Covenant Children's Hospital

    Lubbock, Texas, 79410

  • UMC Cancer Center / UMC Health System

    Lubbock, Texas, 79415

  • Valley Children's Hospital

    Madera, California, 93636

  • University of Wisconsin Carbone Cancer Center - University Hospital

    Madison, Wisconsin, 53792

  • Minnesota Oncology Hematology PA-Maplewood

    Maplewood, Minnesota, 55109

  • Marshfield Medical Center-Marshfield

    Marshfield, Wisconsin, 54449

  • Carle Physician Group-Mattoon/Charleston

    Mattoon, Illinois, 61938

  • Loyola University Medical Center

    Maywood, Illinois, 60153

  • Saint Jude Children's Research Hospital

    Memphis, Tennessee, 38105

  • Banner Children's at Desert

    Mesa, Arizona, 85202

  • University of Miami Miller School of Medicine-Sylvester Cancer Center

    Miami, Florida, 33136

  • Memorial Sloan Kettering Monmouth

    Middletown, New Jersey, 07748

  • Children's Hospitals and Clinics of Minnesota - Minneapolis

    Minneapolis, Minnesota, 55404

  • Abbott-Northwestern Hospital

    Minneapolis, Minnesota, 55407

  • USA Health Strada Patient Care Center

    Mobile, Alabama, 36604

  • Memorial Sloan Kettering Bergen

    Montvale, New Jersey, 07645

  • Morristown Medical Center

    Morristown, New Jersey, 07960

  • The Children's Hospital at TriStar Centennial

    Nashville, Tennessee, 37203

  • Vanderbilt University/Ingram Cancer Center

    Nashville, Tennessee, 37232

  • Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital

    New Brunswick, New Jersey, 08903

  • Rutgers Cancer Institute of New Jersey

    New Brunswick, New Jersey, 08903

  • The Steven and Alexandra Cohen Children's Medical Center of New York

    New Hyde Park, New York, 11040

  • Children's Hospital New Orleans

    New Orleans, Louisiana, 70118

  • Ochsner Medical Center Jefferson

    New Orleans, Louisiana, 70121

  • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

    New York, New York, 10032

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • NYP/Weill Cornell Medical Center

    New York, New York, 10065

  • Corewell Health Lakeland Hospitals - Niles Hospital

    Niles, Michigan, 49120

  • Children's Hospital of The King's Daughters

    Norfolk, Virginia, 23507

  • HSHS Saint Elizabeth's Hospital

    O'Fallon, Illinois, 62269

  • Advocate Children's Hospital-Oak Lawn

    Oak Lawn, Illinois, 60453

  • Kaiser Permanente-Oakland

    Oakland, California, 94611

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • Children's Hospital and Medical Center of Omaha

    Omaha, Nebraska, 68114

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198

  • Children's Hospital of Orange County

    Orange, California, 92868

  • UC Irvine Health/Chao Family Comprehensive Cancer Center

    Orange, California, 92868

  • Arnold Palmer Hospital for Children

    Orlando, Florida, 32806

  • Nemours Children's Hospital

    Orlando, Florida, 32827

  • Lucile Packard Children's Hospital Stanford University

    Palo Alto, California, 94304

  • Advocate Children's Hospital-Park Ridge

    Park Ridge, Illinois, 60068

  • Saint Joseph's Regional Medical Center

    Paterson, New Jersey, 07503

  • OSF Children's Hospital of Illinois

    Peoria, Illinois, 61637

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • Saint Christopher's Hospital for Children

    Philadelphia, Pennsylvania, 19134

  • Children's Hospital of Pittsburgh of UPMC

    Pittsburgh, Pennsylvania, 15224

  • Legacy Emanuel Children's Hospital

    Portland, Oregon, 97227

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • Rhode Island Hospital

    Providence, Rhode Island, 02903

  • Renown Regional Medical Center

    Reno, Nevada, 89502

  • Valley Medical Center

    Renton, Washington, 98055

  • Reid Health

    Richmond, Indiana, 47374

  • VCU Massey Comprehensive Cancer Center

    Richmond, Virginia, 23298

  • Carilion Children's

    Roanoke, Virginia, 24014

  • University of Rochester

    Rochester, New York, 14642

  • Corewell Health Children's

    Royal Oak, Michigan, 48073

  • University of California Davis Comprehensive Cancer Center

    Sacramento, California, 95817

  • Park Nicollet Clinic - Saint Louis Park

    Saint Louis Park, Minnesota, 55416

  • United Hospital

    Saint Paul, Minnesota, 55102

  • Primary Children's Hospital

    Salt Lake City, Utah, 84113

  • Children's Hospital of San Antonio

    San Antonio, Texas, 78207

  • Methodist Children's Hospital of South Texas

    San Antonio, Texas, 78229

  • University of Texas Health Science Center at San Antonio

    San Antonio, Texas, 78229

  • Rady Children's Hospital - San Diego

    San Diego, California, 92123

  • Memorial Health University Medical Center

    Savannah, Georgia, 31404

  • Maine Children's Cancer Program

    Scarborough, Maine, 04074

  • Seattle Children's Hospital

    Seattle, Washington, 98105

  • Siouxland Regional Cancer Center

    Sioux City, Iowa, 51101

  • Sanford USD Medical Center - Sioux Falls

    Sioux Falls, South Dakota, 57117-5134

  • Providence Sacred Heart Medical Center and Children's Hospital

    Spokane, Washington, 99204

  • Southern Illinois University School of Medicine

    Springfield, Illinois, 62702

  • Springfield Clinic

    Springfield, Illinois, 62702

  • Springfield Memorial Hospital

    Springfield, Illinois, 62781

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Siteman Cancer Center-South County

    St Louis, Missouri, 63129

  • Siteman Cancer Center at Christian Hospital

    St Louis, Missouri, 63136

  • Mercy Hospital Saint Louis

    St Louis, Missouri, 63141

  • Johns Hopkins All Children's Hospital

    St. Petersburg, Florida, 33701

  • Stony Brook University Medical Center

    Stony Brook, New York, 11794

  • State University of New York Upstate Medical University

    Syracuse, New York, 13210

  • Mary Bridge Children's Hospital and Health Center

    Tacoma, Washington, 98405

  • Madigan Army Medical Center

    Tacoma, Washington, 98431

  • Tampa General Hospital

    Tampa, Florida, 33606

  • Saint Joseph's Hospital/Children's Hospital-Tampa

    Tampa, Florida, 33607

  • Montefiore Medical Center - Moses Campus

    The Bronx, New York, 10467

  • ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital

    Toledo, Ohio, 43606

  • Banner University Medical Center - Tucson

    Tucson, Arizona, 85719

  • Memorial Sloan Kettering Nassau

    Uniondale, New York, 11553

  • Carle Cancer Center

    Urbana, Illinois, 61801

  • New York Medical College

    Valhalla, New York, 10595

  • Northwestern Medicine Cancer Center Warrenville

    Warrenville, Illinois, 60555

  • MedStar Georgetown University Hospital

    Washington D.C., District of Columbia, 20007

  • Children's National Medical Center

    Washington D.C., District of Columbia, 20010

  • UI Health Care Mission Cancer and Blood - Waukee Clinic

    Waukee, Iowa, 50263

  • Wilmot Cancer Institute at Webster

    Webster, New York, 14580

  • Wesley Medical Center

    Wichita, Kansas, 67214

  • Alfred I duPont Hospital for Children

    Wilmington, Delaware, 19803

  • Wake Forest University Health Sciences

    Winston-Salem, North Carolina, 27157

Other trials in United States

Canada12 sites

  • University of Alberta Hospital

    Edmonton, Alberta, T6G 2B7

  • IWK Health Centre

    Halifax, Nova Scotia, B3K 6R8

  • McMaster Children's Hospital at Hamilton Health Sciences

    Hamilton, Ontario, L8N 3Z5

  • Children's Hospital

    London, Ontario, N6A 5W9

  • The Montreal Children's Hospital of the MUHC

    Montreal, Quebec, H3H 1P3

  • Centre Hospitalier Universitaire Sainte-Justine

    Montreal, Quebec, H3T 1C5

  • Children's Hospital of Eastern Ontario

    Ottawa, Ontario, K1H 8L1

  • CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)

    Québec, G1V 4G2

  • Centre Hospitalier Universitaire de Sherbrooke-Fleurimont

    Sherbrooke, Quebec, J1H 5N4

  • Janeway Child Health Centre

    St. John's, Newfoundland and Labrador, A1B 3V6

  • Hospital for Sick Children

    Toronto, Ontario, M5G 1X8

  • CancerCare Manitoba

    Winnipeg, Manitoba, R3E 0V9

Other trials in Canada

Australia5 sites

  • John Hunter Children's Hospital

    Hunter Regional Mail Centre, New South Wales, 2310

  • Royal Children's Hospital

    Parkville, Victoria, 3052

  • Perth Children's Hospital

    Perth, Western Australia, 6009

  • Queensland Children's Hospital

    South Brisbane, Queensland, 4101

  • The Children's Hospital at Westmead

    Westmead, New South Wales, 2145

Other trials in Australia

Puerto Rico1 site

  • HIMA San Pablo Oncologic Hospital

    Caguas, 00726

Other trials in Puerto Rico

About this study

Official title: 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

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To determine if nivolumab + chemo-immunotherapy results in a superior long term progression-free survival (PFS) (events defined as disease progression confirmed by central review or death) when compared with chemo-immunotherapy alone in patients with newly diagnosed primary mediastinal B-cell lymphoma.

SECONDARY OBJECTIVES:

  1. To compare the rates of "efficacy-related event-free survival (EFS)" (eEFS) (events defined as progression, change in therapy due to finding that led to concern about efficacy, biopsy + disease after 6 cycles of therapy, or death) between chemo-immunotherapy alone and chemo-immunotherapy + nivolumab in patients with newly diagnosed PMBCL.

II. To compare the rates of "therapy-related EFS" (tEFS) (events defined as relapse/progression, change in therapy for any reason, biopsy + disease after 6 cycles of therapy, secondary malignancy [SMN] or death) between chemo-immunotherapy alone and chemo-immunotherapy + nivolumab in patients with newly diagnosed PMBCL.

III. To compare the rates of overall survival (OS) between chemo-immunotherapy alone and chemo-immunotherapy + nivolumab in patients with newly diagnosed PMBCL.

IV. To establish the rate of a positive positron emission tomography (PET)-computed tomography (CT) (defined as Deauville score 4 or 5) at the completion of 6 cycles of nivolumab + rituximab (R)- cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)/dose-adjusted (DA)-etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (EPOCH)-R and R-CHOP/DA-EPOCH-R in patients with newly diagnosed PMBCL and evaluate the prognostic significance of such a finding.

EXPLORATORY OBJECTIVES:

  1. To bank radiology images for further studies. II. To bank specimens for future correlative studies. III. Characterize the immune profile of patients treated with nivolumab + chemo-immunotherapy to identify markers predictive of response.

IV. Define the rate of complete response at the completion of initial planned therapy.

OUTLINE: Patients are randomly assigned to backbone therapy or backbone therapy + nivolumab within each of 6 strata. The strata are determined by physician's choice of backbone (DA-EPOCH-R versus [vs.] R-CHOP vs. R-CHOP + RT) and whether or not the patient had 1 prior cycle of therapy.

ARM A (DA-EPOCH-R): Patients receive prednisone or prednisolone orally (PO) once daily (QD) on days 1-5 and rituximab intravenously (IV) or rituximab and hyaluronidase human subcutaneously (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 absolute neutrophil count (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 undergo echocardiography (ECHO) during screening and as clinically indicated and a lumbar puncture (LP) for cerebral spinal fluid (CSF) collection optionally during screening. Patients also undergo computed tomography (CT) or positron emission tomography (PET)/CT throughout the trial. Additionally, patients undergo bone marrow biopsy and aspiration optionally during screening and as clinically indicated on study. Patients undergo blood sample collection on study.

ARM B (DA-EPOCH-R + NIVOLUMAB): Patients receive treatment as in Arm A. Patients also receive nivolumab IV over 30 minutes on day 1. Patients undergo ECHO during screening and as clinically indicated and LP for CSF collection optionally during screening. Patients also undergo CT or PET/CT throughout the trial. Additionally, patients undergo bone marrow biopsy and aspiration optionally during screening and as clinically indicated on study. Patients undergo blood sample collection on study.

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 undergo ECHO during screening and as clinically indicated and LP for CSF collection optionally during screening. Patients also undergo CT or PET/CT throughout the trial. Additionally, patients undergo bone marrow biopsy and aspiration optionally during screening and as clinically indicated on study. Patients undergo blood sample collection on study.

ARM D (R-CHOP + NIVOLUMAB): Patients receive treatment as in Arm C. Patients also receive nivolumab IV over 30 minutes on day 1. Patients undergo ECHO during screening and as clinically indicated and LP for CSF collection optionally during screening. Patients also undergo CT or PET/CT throughout the trial. Additionally, patients undergo bone marrow biopsy and aspiration optionally during screening and as clinically indicated on study. Patients undergo blood sample collection on study.

ARM E (R-CHOP + RADIOTHERAPY): Patients receive treatment as in Arm C. Within 6-8 weeks after completion of chemotherapy, patients undergo radiation therapy over 25 fractions. Patients undergo ECHO during screening and as clinically indicated and LP for CSF collection optionally during screening. Patients also undergo CT or PET/CT throughout the trial. Additionally, patients undergo bone marrow biopsy and aspiration optionally during screening and as clinically indicated on study. Patients undergo blood sample collection on study.

ARM F (R-CHOP + RADIOTHERAPY + NIVOLUMAB): Patients receive treatment as in Arm D. Within 6-8 weeks after completion of chemotherapy, patients undergo radiation therapy over 25 fractions. Patients undergo ECHO during screening and as clinically indicated and LP for CSF collection optionally during screening. Patients also undergo CT or PET/CT throughout the trial. Additionally, patients undergo bone marrow biopsy and aspiration optionally during screening and as clinically indicated on study. Patients undergo blood sample collection on study.

After completion of study treatment, patients are followed up every 3 months for year 1, every 6 months for years 2-3, and annually thereafter.

Being tested
Biospecimen Collection, Bone Marrow Aspiration, Bone Marrow Biopsy, Computed Tomography, Cyclophosphamide

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo blood and CSF sample collection

  • Bone Marrow AspirationProcedure or surgery

    Undergo bone marrow biopsy and aspiration

  • Bone Marrow BiopsyProcedure or surgery

    Also called Biopsy of Bone Marrow, Biopsy, Bone Marrow

    Undergo bone marrow biopsy and aspiration

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT or PET/CT

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B 518

    Given IV

  • Doxorubicin HydrochlorideDrug

    Also called 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI), ADM, Adriacin, Adriamycin

    Given IV

  • Echocardiography TestProcedure or surgery

    Also called EC, Echocardiography

    Undergo ECHO

  • Etoposide PhosphateDrug

    Also called Etopophos

    Given IV

  • FilgrastimBiological

    Also called Filgrastim Biosimilar Filgrastim-sndz, Filgrastim Biosimilar Tbo-filgrastim, Filgrastim XM02, Filgrastim-aafi

    Given SC

  • Lumbar PunctureProcedure or surgery

    Also called LP, Spinal Tap

    Undergo LP

  • NivolumabBiological

    Also called ABP 206, BCD-263, BMS 936558, BMS-936558

    Given IV

  • PegfilgrastimBiological

    Also called Cegfila, Dulastin, Dyrupeg, Filgrastim SD-01

    Given SC

  • Positron Emission TomographyProcedure or surgery

    Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)

    Undergo PET/CT

  • PrednisoloneDrug

    Also called (11beta)-11,17,21-Trihydroxypregna-1,4-diene-3,20-dione, .delta.1-Hydrocortisone, Adnisolone, Aprednislon

    Given PO

  • PrednisoneDrug

    Also called .delta.1-Cortisone, 1, 2-Dehydrocortisone, Adasone, Cortancyl

    Given PO

  • Radiation TherapyRadiation

    Also called Cancer Radiotherapy, Energy Type, ENERGY_TYPE, Irradiate

    Undergo radiation therapy

  • RituximabBiological

    Also called ABP 798, ABP-798, ABP798, BI 695500

    Given IV

  • Rituximab and Hyaluronidase HumanBiological

    Also called Rituxan Hycela, Rituximab Plus Hyaluronidase, Rituximab/Hyaluronidase, Rituximab/Hyaluronidase Human

    Given SC

  • Vincristine SulfateDrug

    Also called Kyocristine, Leurocristine Sulfate, Leurocristine, sulfate, Oncovin

    Given IV

Study groups in NCT04759586
Study groupRoleWhat they receive
Arm A (DA-EPOCH-R)Active comparatorSee Detailed Description
Receives: Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Drug: Cyclophosphamide; Drug: Doxorubicin Hydrochloride; Procedure: Echocardiography Test; Drug: Etoposide Phosphate; Biological: Filgrastim; Procedure: Lumbar Puncture; Biological: Pegfilgrastim; Procedure: Positron Emission Tomography; Drug: Prednisolone; Drug: Prednisone; Biological: Rituximab; Biological: Rituximab and Hyaluronidase Human; Drug: Vincristine Sulfate
Arm B (DA-EPOCH-R, nivolumab)ExperimentalPatients 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 undergo ECHO and LP for CSF collection during screening. Patients undergo ECHO during screening and as clinically indicated and LP for CSF collection optionally during screening. Patients also undergo CT or PET/CT throughout the trial. Additionally, patients undergo bone marrow biopsy and aspiration optionally during screening and as clinically indicated on study. Patients undergo blood sample collection on study.
Receives: Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Drug: Cyclophosphamide; Drug: Doxorubicin Hydrochloride; Procedure: Echocardiography Test; Drug: Etoposide Phosphate; Biological: Filgrastim; Procedure: Lumbar Puncture; Biological: Nivolumab; Biological: Pegfilgrastim; Procedure: Positron Emission Tomography; Drug: Prednisolone; Drug: Prednisone; Biological: Rituximab; Biological: Rituximab and Hyaluronidase Human; Drug: Vincristine Sulfate
Arm C (R-CHOP)Active comparatorPatients 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 undergo ECHO during screening and as clinically indicated and LP for CSF collection optionally during screening. Patients also undergo CT or PET/CT throughout the trial. Additionally, patients undergo bone marrow biopsy and aspiration optionally during screening and as clinically indicated on study. Patients undergo blood sample collection on study.
Receives: Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Drug: Cyclophosphamide; Drug: Doxorubicin Hydrochloride; Procedure: Echocardiography Test; Procedure: Lumbar Puncture; Procedure: Positron Emission Tomography; Drug: Prednisolone; Drug: Prednisone; Biological: Rituximab; Biological: Rituximab and Hyaluronidase Human; Drug: Vincristine Sulfate
Arm D (R-CHOP, nivolumab)ExperimentalPatients 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 undergo ECHO during screening and as clinically indicated and LP for CSF collection optionally during screening. Patients also undergo CT or PET/CT throughout the trial. Additionally, patients undergo bone marrow biopsy and aspiration optionally during screening and as clinically indicated on study. Patients undergo blood sample collection on study.
Receives: Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Drug: Cyclophosphamide; Drug: Doxorubicin Hydrochloride; Procedure: Echocardiography Test; Procedure: Lumbar Puncture; Biological: Nivolumab; Procedure: Positron Emission Tomography; Drug: Prednisolone; Drug: Prednisone; Biological: Rituximab; Biological: Rituximab and Hyaluronidase Human; Drug: Vincristine Sulfate
Arm E (R-CHOP, radiation therapy)Active comparatorPatients receive treatment as in Arm C. Within 6-8 weeks after completion of chemotherapy, patients undergo radiation therapy over 25 fractions. Patients undergo ECHO during screening and as clinically indicated and LP for CSF collection optionally during screening. Patients also undergo CT or PET/CT throughout the trial. Additionally, patients undergo bone marrow biopsy and aspiration optionally during screening and as clinically indicated on study. Patients undergo blood sample collection on study.
Receives: Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Drug: Cyclophosphamide; Drug: Doxorubicin Hydrochloride; Procedure: Echocardiography Test; Procedure: Lumbar Puncture; Procedure: Positron Emission Tomography; Drug: Prednisolone; Drug: Prednisone; Radiation: Radiation Therapy; Biological: Rituximab; Biological: Rituximab and Hyaluronidase Human; Drug: Vincristine Sulfate
Arm F (R-CHOP, nivolumab, radiation therapy)ExperimentalPatients receive treatment as in Arm D. Within 6-8 weeks after completion of chemotherapy, patients undergo radiation therapy over 25 fractions. Patients undergo ECHO during screening and as clinically indicated and LP for CSF collection optionally during screening. Patients also undergo CT or PET/CT throughout the trial. Additionally, patients undergo bone marrow biopsy and aspiration optionally during screening and as clinically indicated on study. Patients undergo blood sample collection on study.
Receives: Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Drug: Cyclophosphamide; Drug: Doxorubicin Hydrochloride; Procedure: Echocardiography Test; Procedure: Lumbar Puncture; Biological: Nivolumab; Procedure: Positron Emission Tomography; Drug: Prednisolone; Drug: Prednisone; Radiation: Radiation Therapy; Biological: Rituximab; Biological: Rituximab and Hyaluronidase Human

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-free survival (PFS)

    The primary analysis will be a one-sided Log-rank test stratified by choice of backbone and radiation therapy and whether the patient had a cycle of therapy prior to enrolling.

    Measured: From enrollment on the study to first occurrence of relapse/progression or death, assessed up to 7 years

Secondary outcomes (4)

  1. Efficacy-related event-free survival

    Will be analyzed using a one-sided stratified Log-rank test at alpha = 0.05 or 0.025, as appropriate, with events defined as progression, change in therapy due to a finding that led to concern about efficacy, biopsy + disease after 6 cycles of therapy, and death.

    Measured: Up to 7 years

  2. Therapy-related event-free survival

    Will be analyzed using a one-sided stratified Log-rank test at alpha = 0.05 or 0.025, as appropriate, with events defined as progression, change in therapy due to a finding that led to concern about efficacy, biopsy + disease after 6 cycles of therapy, and death.

    Measured: Up to 7 years

  3. Overall survival

    Will be analyzed using a one-sided stratified Log-rank test at alpha = 0.05 or 0.025, as appropriate, with events defined as only death.

    Measured: Up to 7 years

  4. Proportion of positive positron emission tomography (PET) scans

    Will be analyzed descriptively with a point estimate and Clopper-Pearson 95% confidence interval in the trial overall and in each treatment arm separately. The prognostic significance of positive PET after 6 cycles of therapy will be evaluated using a Cox proportional hazards regression on PFS with PET result (positive versus [vs.] negative), choice of backbone (rituximab [R]-cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP] + radiation therapy [RT] regardless of end-of-therapy imaging vs. R-CHOP without RT unless biopsy positive at end-of-therapy vs. dose-adjusted [DA]-etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin [EPOCH]-R without RT unless biopsy positive at end of therapy), and assignment to nivolumab (yes vs. no) as covariates.

    Measured: Up to 6 cycle (1 cycle = 21 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Feb 2021
  2. Study start5 Oct 2021
  3. Primary completion30 Jun 2027 (estimated)
  4. Study completion30 Jun 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
244 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04759586
Sponsor's protocol ID
NCI-2021-01071
Other IDs
NCI-2021-01071, ANHL1931, ANHL1931, U10CA180886
Status last verified
Nov 2026
First submitted
17 Feb 2021
Last updated
4 Nov 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Biospecimen Collection, Bone Marrow Aspiration and Bone Marrow Biopsy in people with Primary Mediastinal Large B-Cell Lymphoma, run by National Cancer Institute (NCI) at 233 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 4 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 233 sites in United States, Canada, Australia, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free survival (PFS) (time frame: From enrollment on the study to first occurrence of relapse/progression or death, assessed up to 7 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04759586.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2026; AzTrials last refreshed its copy on 8 Nov 2026.

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