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Testing Continuous Versus Intermittent Treatment With the Study Drug Zanubrutinib for Older Patients With Previously Untreated Mantle Cell Lymphoma

RecruitingPhase 3

A Randomized Phase 3 Trial of Continuous vs. Intermittent Maintenance Therapy With Zanubrutinib as Upfront Treatment in Older Patients With Mantle Cell Lymphoma

Who can join

Ages 60 and older · All sexes

Full eligibility criteria
Inclusion Criteria:

* • Histologically confirmed mantle cell lymphoma with cyclin D1 (BCL1) expression by immunohistochemical stains and/or evidence of CCND1 rearrangement or t(11;14)(q13;q32) as confirmed by the enrolling center (such as by fluorescence in situ hybridization \[FISH\], polymerase chain reaction \[PCR\]/sequencing, karyotype). Patients with cyclin D1 and/or t(11;14) negative mantle cell lymphoma with an expression profile suggesting a diagnosis of mantle cell lymphoma \[MCL\] such as SOX11 expression are also eligible

  * Any stage allowed (stage I-IV)

    * Patient must have at least one objective measurable disease parameter by PET or CT. Measurable disease in the liver is required if the liver is the only site of lymphoma OR bone marrow involvement by MCL
    * Steroids for management of mantle cell lymphoma are allowed up to a dose of prednisone 100mg/day (or equivalent) for up to 7 days prior to registration
    * No prior systemic treatment for mantle cell lymphoma
    * No prior radiation treatment for stage I MCL
    * No prior exposure to a BTK inhibitor or anti-CD20 monoclonal antibody
    * No prior stem cell transplant
    * Age \>= 70 years OR age \>= 60 to \< 70 years with comorbidities precluding autologous stem cell transplantation (autoSCT) including at least one of the following: a) cardiac ejection fraction (EF) \<= 45%, b) diffusing capacity for carbon monoxide \<= 60% predicted; c) creatinine clearance \< 70 but \>= 30ml/minute (min); d) Eastern Cooperative Oncology Group (ECOG) performance status of 2, which poses an unacceptable risk of toxicity for high-dose therapy and stem cell transplantation; or e) Cumulative Illness Rating Scales (CIRS) total score \> 6
    * ECOG Performance Status 0-2
    * Absolute neutrophil count (ANC) \>= 750/mm\^3 (without growth factor support within 7 days)
    * Platelet count \>= 75,000/mm\^3 (or \>= 50,000/mm\^3 if thrombocytopenia is due to lymphoma) without growth factor support or transfusion within 7 days
    * Creatinine clearance \>= 30 mL/ min determined by either: a) Estimation using the Cockcroft-Gault equation or b) Measurement by nuclear medicine scan or 24 hour urine collection
    * Total bilirubin =\< 1.5 x upper limit of normal (ULN) (unless documented Gilbert's syndrome)
    * Aspartate transferase (AST) / alanine transaminase (ALT) =\< 3 x ULN
    * Patients should not be considered candidates for stem cell transplant or must have declined a stem cell transplant strategy
    * No clinically significant cardiovascular disease including the following
  * Unstable angina within 3 months before registration
  * New York Heart Association class III or IV congestive heart failure
  * History of clinically significant arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes)
  * Known QT correction formula (QTcF) \> 480 msecs based on Fredericia's formula (unless pacemaker in place)
  * History of Mobitz II second-degree or third-degree heart block without a permanent pacemaker in place

    * Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
    * No active Hepatitis B or Hepatitis C infection. Patients with prior hepatitis B virus (HBV) exposure (positive HBV core antibody and/or surface antigen) are eligible if they have no detectable viral load, and are taking appropriate prophylactic antiviral therapy to prevent reactivation. Patients with history of hepatitis C virus (HCV) are eligible if they have an undetectable HCV viral load
    * Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
    * No history of severe bleeding disorder such as hemophilia A, hemophilia B, von Willebrand disease, or history of spontaneous bleeding requiring blood transfusion or other medical intervention
    * No history of stroke or intracranial hemorrhage within 6 months prior to registration
    * No disease significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, bariatric surgery procedures, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction. Patient must be able to swallow pills
    * Potential trial participants should have recovered from major surgery
    * No vaccination with a live vaccine within 35 days prior to registration
    * No hypersensitivity to zanubrutinib or rituximab or any of the other ingredients of the study drugs
    * Patients on strong CYP3A4 inhibitors must discontinue the drug for 14 days prior to registration on the study.
    * Patients on strong CYP3A4 inducers must discontinue the drug 14 days prior to registration.

About the study

This phase III trial tests whether continuous or intermittent zanubrutinib after achieving a complete remission (CR) with rituximab works in older adult patients with mantle cell lymphoma (MCL) who have not received treatment in the past (previously untreated). Rituximab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Zanubrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. When zanubrutinib is used in MCL, the current standard of care is to continue administering the drug indefinitely until disease progression. This continuous treatment comes with clinical as well as financial toxicity, which could be especially detrimental in older patients. For patients who achieve a CR after initial zanubrutinib plus rituximab therapy, it may be safe and equally effective to stop treatment and restart zanubrutinib upon disease progression rather than continuing indefinitely in previously untreated older adult patients with MCL.

What is being tested

Sponsor: Alliance for Clinical Trials in Oncology · Participants: 421 · Started: Oct 20, 2023

Contact the study team

Official record on ClinicalTrials.gov — NCT05976763

Locations in the U.S.

ArkansasUniversity of Arkansas for Medical Sciences, Little Rock
CaliforniaTower Cancer Research Foundation, Beverly Hills
Cedars-Sinai Medical Center, Los Angeles
ConnecticutSmilow Cancer Hospital-Derby Care Center, Derby
Smilow Cancer Hospital Care Center-Fairfield, Fairfield
Smilow Cancer Hospital Care Center at Glastonbury, Glastonbury
Smilow Cancer Hospital Care Center at Greenwich, Greenwich
Smilow Cancer Hospital Care Center - Guilford, Guilford
Smilow Cancer Hospital Care Center at Saint Francis, Hartford
Yale University, New Haven
Yale-New Haven Hospital North Haven Medical Center, North Haven
Smilow Cancer Hospital Care Center at Long Ridge, Stamford
Smilow Cancer Hospital-Torrington Care Center, Torrington
Smilow Cancer Hospital Care Center-Trumbull, Trumbull
Smilow Cancer Hospital-Waterbury Care Center, Waterbury
Smilow Cancer Hospital Care Center - Waterford, Waterford
DelawareHelen F Graham Cancer Center, Newark
Medical Oncology Hematology Consultants PA, Newark
GeorgiaPhoebe Putney Memorial Hospital, Albany
Emory Saint Joseph's Hospital, Atlanta
Emory University Hospital Midtown, Atlanta
Emory University Hospital/Winship Cancer Institute, Atlanta
Grady Health System, Atlanta
Augusta University Medical Center, Augusta
Emory Johns Creek Hospital, Johns Creek
IdahoSaint Alphonsus Cancer Care Center-Boise, Boise
Saint Luke's Cancer Institute - Boise, Boise
Saint Alphonsus Cancer Care Center-Caldwell, Caldwell
Kootenai Health - Coeur d'Alene, Coeur d'Alene
Saint Luke's Cancer Institute - Fruitland, Fruitland
Saint Luke's Cancer Institute - Meridian, Meridian
Saint Alphonsus Cancer Care Center-Nampa, Nampa
Saint Luke's Cancer Institute - Nampa, Nampa
Kootenai Clinic Cancer Services - Post Falls, Post Falls
Kootenai Clinic Cancer Services - Sandpoint, Sandpoint
IllinoisIllinois CancerCare-Bloomington, Bloomington
Illinois CancerCare-Canton, Canton
Illinois CancerCare-Carthage, Carthage
Alliance for Clinical Trials in Oncology, Chicago
University of Illinois, Chicago
Carle at The Riverfront, Danville
Cancer Care Specialists of Illinois - Decatur, Decatur
Decatur Memorial Hospital, Decatur
Illinois CancerCare-Dixon, Dixon
Carle Physician Group-Effingham, Effingham
Crossroads Cancer Center, Effingham
Illinois CancerCare-Eureka, Eureka
Illinois CancerCare-Galesburg, Galesburg
Illinois CancerCare-Kewanee Clinic, Kewanee
Illinois CancerCare-Macomb, Macomb
Carle Physician Group-Mattoon/Charleston, Mattoon
SSM Health Good Samaritan, Mount Vernon
Cancer Care Center of O'Fallon, O'Fallon
Illinois CancerCare-Ottawa Clinic, Ottawa
Illinois CancerCare-Pekin, Pekin
Illinois CancerCare-Peoria, Peoria
Illinois CancerCare-Peru, Peru
Illinois CancerCare-Princeton, Princeton
Memorial Hospital East, Shiloh
Southern Illinois University School of Medicine, Springfield
Springfield Clinic, Springfield
Springfield Memorial Hospital, Springfield
Carle Cancer Center, Urbana
Illinois CancerCare - Washington, Washington
IndianaNorthwest Cancer Center - Crown Point, Crown Point
Northwest Oncology LLC, Dyer
Northwest Cancer Center - Hobart, Hobart
Saint Mary Medical Center, Hobart
Saint Catherine Hospital, Indianapolis
The Community Hospital, Munster
Women's Diagnostic Center - Munster, Munster
Northwest Cancer Center - Valparaiso, Valparaiso
IowaMary Greeley Medical Center, Ames
McFarland Clinic - Ames, Ames
UI Health Care Mission Cancer and Blood - Ankeny Clinic, Ankeny
Saint Anthony Regional Hospital, Carroll
UI Health Care Mission Cancer and Blood - West Des Moines Clinic, Clive
Broadlawns Medical Center, Des Moines
Iowa Methodist Medical Center, Des Moines
Mercy Medical Center - Des Moines, Des Moines
UI Health Care Mission Cancer and Blood - Des Moines Clinic, Des Moines
UI Health Care Mission Cancer and Blood - Laurel Clinic, Des Moines
McFarland Clinic - Trinity Cancer Center, Fort Dodge
UI Healthcare Mission Cancer and Blood - Fort Dodge, Fort Dodge
University of Iowa/Holden Comprehensive Cancer Center, Iowa City
McFarland Clinic - Marshalltown, Marshalltown
UI Health Care Mission Cancer and Blood - Waukee Clinic, Waukee
KansasHaysMed, Hays
University of Kansas Cancer Center, Kansas City
Lawrence Memorial Hospital, Lawrence
Veteran Administration Eastern Kansas Healthcare, Leavenworth
The University of Kansas Cancer Center - Olathe, Olathe
University of Kansas Cancer Center-Overland Park, Overland Park
Freeman Physician Group of Pittsburg, Pittsburg
Salina Regional Health Center, Salina
University of Kansas Health System Saint Francis Campus, Topeka
University of Kansas Hospital-Westwood Cancer Center, Westwood
KentuckyThe James Graham Brown Cancer Center at University of Louisville, Louisville
UofL Health Medical Center Northeast, Louisville
MichiganTrinity Health Saint Joseph Mercy Hospital Ann Arbor, Ann Arbor
McLaren Cancer Institute-Bay City, Bay City
Trinity Health IHA Medical Group Hematology Oncology - Brighton, Brighton
Trinity Health Medical Center - Brighton, Brighton
Trinity Health IHA Medical Group Hematology Oncology - Canton, Canton
Trinity Health Medical Center - Canton, Canton
Chelsea Hospital, Chelsea
Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital, Chelsea
McLaren Cancer Institute-Clarkston, Clarkston
Wayne State University/Karmanos Cancer Institute, Detroit
Corewell Health Farmington Hills Hospital, Farmington Hills
Weisberg Cancer Treatment Center, Farmington Hills
Cancer Hematology Centers - Flint, Flint
Genesys Hurley Cancer Institute, Flint
Hurley Medical Center, Flint
McLaren Cancer Institute-Flint, Flint
University of Michigan Health - Sparrow Lansing, Lansing
McLaren Cancer Institute-Lapeer Region, Lapeer
Trinity Health Saint Mary Mercy Livonia Hospital, Livonia
Henry Ford Saint John Hospital - Macomb Medical, Macomb
McLaren Cancer Institute-Central Michigan, Mount Pleasant
McLaren Cancer Institute-Northern Michigan, Petoskey
Trinity Health Saint Joseph Mercy Oakland Hospital, Pontiac
Corewell Health William Beaumont University Hospital, Royal Oak
MyMichigan Medical Center Saginaw, Saginaw
MyMichigan Medical Center Tawas, Tawas City
Corewell Health Beaumont Troy Hospital, Troy
Huron Gastroenterology PC, Ypsilanti
Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus, Ypsilanti
MinnesotaSanford Joe Lueken Cancer Center, Bemidji
Essentia Health Saint Joseph's Medical Center, Brainerd
Mercy Hospital, Coon Rapids
Essentia Health - Deer River Clinic, Deer River
Essentia Health Cancer Center, Duluth
Essentia Health Hibbing Clinic, Hibbing
Saint John's Hospital - Healtheast, Maplewood
Abbott-Northwestern Hospital, Minneapolis
Hennepin County Medical Center, Minneapolis
Coborn Cancer Center at Saint Cloud Hospital, Saint Cloud
Park Nicollet Clinic - Saint Louis Park, Saint Louis Park
Regions Hospital, Saint Paul
United Hospital, Saint Paul
Essentia Health Sandstone, Sandstone
Essentia Health Virginia Clinic, Virginia
Minnesota Oncology Hematology PA-Woodbury, Woodbury
MissouriSaint Francis Medical Center, Cape Girardeau
Saint Luke's Hospital, Chesterfield
Siteman Cancer Center at Saint Peters Hospital, City of Saint Peters
Siteman Cancer Center at West County Hospital, Creve Coeur
Kansas City Veterans Affairs Medical Center, Kansas City
University Health Truman Medical Center, Kansas City
University of Kansas Cancer Center - Briarcliff, Kansas City
University of Kansas Cancer Center - North, Kansas City
University of Kansas Cancer Center - Lee's Summit, Lee's Summit
CoxHealth South Hospital, Springfield
Mercy Hospital Springfield, Springfield
Mercy Hospital South, St Louis
Siteman Cancer Center at Christian Hospital, St Louis
Siteman Cancer Center-South County, St Louis
Washington University School of Medicine, St Louis
MontanaCommunity Hospital of Anaconda, Anaconda
Billings Clinic Cancer Center, Billings
Bozeman Health Deaconess Hospital, Bozeman
Benefis Sletten Cancer Institute, Great Falls
Logan Health Medical Center, Kalispell
Community Medical Center, Missoula
NebraskaNebraska Medicine-Bellevue, Bellevue
Fred and Pamela Buffett Cancer Center - Kearney, Kearney
Nebraska Medicine-Village Pointe, Omaha
University of Nebraska Medical Center, Omaha
New HampshireDartmouth Hitchcock Medical Center/Dartmouth Cancer Center, Lebanon
New YorkRoswell Park Cancer Institute, Buffalo
Hematology Oncology Associates of CNY at Camillus, Camillus
Hematology Oncology Associates of Central New York-East Syracuse, East Syracuse
NYU Langone Hospital - Long Island, Mineola
Laura and Isaac Perlmutter Cancer Center at NYU Langone, New York
NYP/Weill Cornell Medical Center, New York
University of Rochester, Rochester
Wilmot Cancer Institute at Webster, Webster
North CarolinaUNC Lineberger Comprehensive Cancer Center, Chapel Hill
Duke University Medical Center, Durham
North DakotaSanford Bismarck Medical Center, Bismarck
Essentia Health Cancer Center-South University Clinic, Fargo
Sanford Broadway Medical Center, Fargo
Sanford Roger Maris Cancer Center, Fargo
OhioOhio State University Comprehensive Cancer Center, Columbus
OklahomaCancer Centers of Southwest Oklahoma Research, Lawton
University of Oklahoma Health Sciences Center, Oklahoma City
Oklahoma Cancer Specialists and Research Institute-Tulsa, Tulsa
OregonProvidence Newberg Medical Center, Newberg
Saint Alphonsus Cancer Care Center-Ontario, Ontario
Providence Willamette Falls Medical Center, Oregon City
Providence Portland Medical Center, Portland
Providence Saint Vincent Medical Center, Portland
Rhode IslandRhode Island Hospital, Providence
Smilow Cancer Hospital Care Center - Westerly, Westerly
South CarolinaPrisma Health Cancer Institute - Spartanburg, Boiling Springs
Medical University of South Carolina, Charleston
Prisma Health Cancer Institute - Easley, Easley
Prisma Health Cancer Institute - Butternut, Greenville
Prisma Health Cancer Institute - Eastside, Greenville
Prisma Health Cancer Institute - Faris, Greenville
Prisma Health Cancer Institute - Greer, Greer
Prisma Health Cancer Institute - Seneca, Seneca
South DakotaSanford Cancer Center Oncology Clinic, Sioux Falls
Sanford USD Medical Center - Sioux Falls, Sioux Falls
UtahHuntsman Cancer Institute/University of Utah, Salt Lake City
VermontDartmouth Cancer Center - North, Saint Johnsbury
VirginiaVCU Massey Cancer Center at Stony Point, Richmond
VCU Massey Comprehensive Cancer Center, Richmond
WashingtonSwedish Cancer Institute-Edmonds, Edmonds
Swedish Cancer Institute-Issaquah, Issaquah
Swedish Medical Center-First Hill, Seattle
WisconsinThedaCare Regional Cancer Center, Appleton
ThedaCare Regional Medical Center - Appleton, Appleton
Duluth Clinic Ashland, Ashland
Marshfield Medical Center-EC Cancer Center, Eau Claire
University of Wisconsin Carbone Cancer Center - Johnson Creek, Johnson Creek
Gundersen Lutheran Medical Center, La Crosse
University of Wisconsin Carbone Cancer Center - Eastpark Medical Center, Madison
University of Wisconsin Carbone Cancer Center - University Hospital, Madison
Marshfield Medical Center-Marshfield, Marshfield
Medical College of Wisconsin, Milwaukee
Marshfield Medical Center - Minocqua, Minocqua
Froedtert and MCW Moorland Reserve Health Center, New Berlin
Marshfield Medical Center-Rice Lake, Rice Lake
Marshfield Medical Center-River Region at Stevens Point, Stevens Point
Marshfield Medical Center - Weston, Weston

Conditions

From ClinicalTrials.gov, data retrieved Sep 30, 2026. Each study sets its own eligibility; the study team decides who can join.