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

Status: Recruiting
Location: See all (227) locations...
Intervention Type: Procedure, Biological, Other, Drug
Study Type: Interventional
Study Phase: Phase 3
SUMMARY

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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 60
Healthy Volunteers: f
View:

• • Histologically confirmed mantle cell lymphoma with cyclin D1 (BCL1) expression by immunohistochemical stains and/or t(11;14) by cytogenetics or fluorescence in situ hybridization (FISH) as confirmed by the enrolling center

‣ Any stage allowed (stage I-IV)

• Presence of measurable disease, defined as \>= 1 nodal lesion that is \> 1.5 cm in longest diameter or \>= 1 extranodal lesion that is \> 1 cm in longest diameter

∙ Steroids for management of mantle cell lymphoma are allowed up to a dose of prednisone 100mg/day (or equivalent) for up to 7 days

∙ 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 for patients with bone marrow involvement of 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)

⁃ QT correction formula (QTcF) \> 480 msecs based on Fredericia's formula

⁃ 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

∙ Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on this study. Patients on strong CYP3A4 inhibitors must discontinue the drug for 14 days prior to registration on the study.

∙ Chronic concomitant treatment with strong CYP3A4 inducers is not allowed. Patients must discontinue the drug 14 days prior to the start of study treatment

∙ Avoid use of moderate CYP3A4 inhibitors, PGP inhibitors, and moderate CYP3A4 inducers

∙ Archival tissue must be available for submission in all patients for histopathology review, though participation in correlative substudies is optional

Locations
United States
Arkansas
University of Arkansas for Medical Sciences
RECRUITING
Little Rock
California
Tower Cancer Research Foundation
RECRUITING
Beverly Hills
City of Hope Comprehensive Cancer Center
RECRUITING
Duarte
City of Hope at Irvine Lennar
RECRUITING
Irvine
Cedars Sinai Medical Center
RECRUITING
Los Angeles
Connecticut
Smilow Cancer Hospital-Derby Care Center
RECRUITING
Derby
Smilow Cancer Hospital Care Center-Fairfield
RECRUITING
Fairfield
Smilow Cancer Hospital Care Center at Glastonbury
RECRUITING
Glastonbury
Smilow Cancer Hospital Care Center at Greenwich
RECRUITING
Greenwich
Smilow Cancer Hospital Care Center - Guilford
RECRUITING
Guilford
Smilow Cancer Hospital Care Center at Saint Francis
RECRUITING
Hartford
Yale University
RECRUITING
New Haven
Yale-New Haven Hospital North Haven Medical Center
RECRUITING
North Haven
Smilow Cancer Hospital Care Center at Long Ridge
RECRUITING
Stamford
Smilow Cancer Hospital-Torrington Care Center
RECRUITING
Torrington
Smilow Cancer Hospital Care Center-Trumbull
RECRUITING
Trumbull
Smilow Cancer Hospital-Waterbury Care Center
RECRUITING
Waterbury
Smilow Cancer Hospital Care Center - Waterford
RECRUITING
Waterford
Delaware
Helen F Graham Cancer Center
RECRUITING
Newark
Medical Oncology Hematology Consultants PA
RECRUITING
Newark
Georgia
Emory Saint Joseph's Hospital
RECRUITING
Atlanta
Emory University Hospital Midtown
RECRUITING
Atlanta
Emory University Hospital/Winship Cancer Institute
RECRUITING
Atlanta
Grady Health System
RECRUITING
Atlanta
Augusta University Medical Center
RECRUITING
Augusta
Emory Johns Creek Hospital
RECRUITING
Johns Creek
Iowa
Mary Greeley Medical Center
RECRUITING
Ames
McFarland Clinic - Ames
RECRUITING
Ames
UI Health Care Mission Cancer and Blood - Ankeny Clinic
RECRUITING
Ankeny
McFarland Clinic - Boone
RECRUITING
Boone
Saint Anthony Regional Hospital
RECRUITING
Carroll
UI Health Care Mission Cancer and Blood - West Des Moines Clinic
RECRUITING
Clive
Broadlawns Medical Center
RECRUITING
Des Moines
Iowa Methodist Medical Center
RECRUITING
Des Moines
Mercy Medical Center - Des Moines
RECRUITING
Des Moines
UI Health Care Mission Cancer and Blood - Des Moines Clinic
RECRUITING
Des Moines
UI Health Care Mission Cancer and Blood - Laurel Clinic
RECRUITING
Des Moines
McFarland Clinic - Trinity Cancer Center
RECRUITING
Fort Dodge
UI Healthcare Mission Cancer and Blood - Fort Dodge
RECRUITING
Fort Dodge
University of Iowa/Holden Comprehensive Cancer Center
RECRUITING
Iowa City
McFarland Clinic - Jefferson
RECRUITING
Jefferson
McFarland Clinic - Marshalltown
RECRUITING
Marshalltown
UI Health Care Mission Cancer and Blood - Waukee Clinic
RECRUITING
Waukee
Idaho
Saint Alphonsus Cancer Care Center-Boise
RECRUITING
Boise
Saint Luke's Cancer Institute - Boise
RECRUITING
Boise
Saint Alphonsus Cancer Care Center-Caldwell
RECRUITING
Caldwell
Kootenai Health - Coeur d'Alene
RECRUITING
Coeur D'alene
Saint Luke's Cancer Institute - Fruitland
RECRUITING
Fruitland
Saint Luke's Cancer Institute - Meridian
RECRUITING
Meridian
Saint Alphonsus Cancer Care Center-Nampa
RECRUITING
Nampa
Saint Luke's Cancer Institute - Nampa
RECRUITING
Nampa
Kootenai Clinic Cancer Services - Post Falls
RECRUITING
Post Falls
Kootenai Clinic Cancer Services - Sandpoint
RECRUITING
Sandpoint
Illinois
Illinois CancerCare-Bloomington
RECRUITING
Bloomington
Illinois CancerCare-Canton
RECRUITING
Canton
Illinois CancerCare-Carthage
RECRUITING
Carthage
University of Illinois
RECRUITING
Chicago
Carle at The Riverfront
RECRUITING
Danville
Cancer Care Specialists of Illinois - Decatur
RECRUITING
Decatur
Decatur Memorial Hospital
RECRUITING
Decatur
Illinois CancerCare-Dixon
RECRUITING
Dixon
Carle Physician Group-Effingham
RECRUITING
Effingham
Crossroads Cancer Center
RECRUITING
Effingham
Illinois CancerCare-Eureka
RECRUITING
Eureka
Illinois CancerCare-Galesburg
RECRUITING
Galesburg
Illinois CancerCare-Kewanee Clinic
RECRUITING
Kewanee
Illinois CancerCare-Macomb
RECRUITING
Macomb
Carle Physician Group-Mattoon/Charleston
RECRUITING
Mattoon
Cancer Care Center of O'Fallon
RECRUITING
O'fallon
Illinois CancerCare-Ottawa Clinic
RECRUITING
Ottawa
Illinois CancerCare-Pekin
RECRUITING
Pekin
Illinois CancerCare-Peoria
RECRUITING
Peoria
Illinois CancerCare-Peru
RECRUITING
Peru
Illinois CancerCare-Princeton
RECRUITING
Princeton
Memorial Hospital East
RECRUITING
Shiloh
Southern Illinois University School of Medicine
RECRUITING
Springfield
Springfield Clinic
RECRUITING
Springfield
Springfield Memorial Hospital
RECRUITING
Springfield
Carle Cancer Center
RECRUITING
Urbana
Illinois CancerCare - Washington
RECRUITING
Washington
Indiana
Northwest Cancer Center - Main Campus
RECRUITING
Crown Point
Northwest Oncology LLC
RECRUITING
Dyer
Northwest Cancer Center - Hobart
RECRUITING
Hobart
Saint Mary Medical Center
RECRUITING
Hobart
Saint Catherine Hospital
RECRUITING
Indianapolis
The Community Hospital
RECRUITING
Munster
Women's Diagnostic Center - Munster
RECRUITING
Munster
Northwest Cancer Center - Valparaiso
RECRUITING
Valparaiso
Kansas
HaysMed
RECRUITING
Hays
University of Kansas Cancer Center
RECRUITING
Kansas City
Lawrence Memorial Hospital
RECRUITING
Lawrence
The University of Kansas Cancer Center - Olathe
RECRUITING
Olathe
University of Kansas Cancer Center-Overland Park
RECRUITING
Overland Park
Freeman Physician Group of Pittsburg
RECRUITING
Pittsburg
Salina Regional Health Center
RECRUITING
Salina
University of Kansas Health System Saint Francis Campus
RECRUITING
Topeka
University of Kansas Hospital-Westwood Cancer Center
RECRUITING
Westwood
Massachusetts
Alliance for Clinical Trials in Oncology
RECRUITING
Boston
Michigan
Trinity Health Saint Joseph Mercy Hospital Ann Arbor
RECRUITING
Ann Arbor
McLaren Cancer Institute-Bay City
RECRUITING
Bay City
Trinity Health IHA Medical Group Hematology Oncology - Brighton
RECRUITING
Brighton
Trinity Health Medical Center - Brighton
RECRUITING
Brighton
Trinity Health IHA Medical Group Hematology Oncology - Canton
RECRUITING
Canton
Trinity Health Medical Center - Canton
RECRUITING
Canton
Chelsea Hospital
RECRUITING
Chelsea
Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
RECRUITING
Chelsea
McLaren Cancer Institute-Clarkston
RECRUITING
Clarkston
Wayne State University/Karmanos Cancer Institute
RECRUITING
Detroit
Corewell Health Farmington Hills Hospital
RECRUITING
Farmington Hills
Weisberg Cancer Treatment Center
RECRUITING
Farmington Hills
Cancer Hematology Centers - Flint
RECRUITING
Flint
Genesee Hematology Oncology PC
SUSPENDED
Flint
Genesys Hurley Cancer Institute
RECRUITING
Flint
Hurley Medical Center
RECRUITING
Flint
McLaren Cancer Institute-Flint
RECRUITING
Flint
McLaren Cancer Institute-Lapeer Region
RECRUITING
Lapeer
Trinity Health Saint Mary Mercy Livonia Hospital
RECRUITING
Livonia
Henry Ford Saint John Hospital - Macomb Medical
RECRUITING
Macomb
McLaren Cancer Institute-Central Michigan
RECRUITING
Mount Pleasant
McLaren Cancer Institute-Northern Michigan
RECRUITING
Petoskey
Trinity Health Saint Joseph Mercy Oakland Hospital
RECRUITING
Pontiac
Corewell Health William Beaumont University Hospital
RECRUITING
Royal Oak
MyMichigan Medical Center Saginaw
RECRUITING
Saginaw
Oncology Hematology Associates of Saginaw Valley PC
SUSPENDED
Saginaw
MyMichigan Medical Center Tawas
RECRUITING
Tawas City
Corewell Health Beaumont Troy Hospital
RECRUITING
Troy
Saint Mary's Oncology/Hematology Associates of West Branch
SUSPENDED
West Branch
Huron Gastroenterology PC
RECRUITING
Ypsilanti
Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
RECRUITING
Ypsilanti
Minnesota
Sanford Joe Lueken Cancer Center
RECRUITING
Bemidji
Essentia Health Saint Joseph's Medical Center
RECRUITING
Brainerd
Mercy Hospital
RECRUITING
Coon Rapids
Essentia Health - Deer River Clinic
RECRUITING
Deer River
Essentia Health Cancer Center
RECRUITING
Duluth
Essentia Health Hibbing Clinic
RECRUITING
Hibbing
Saint John's Hospital - Healtheast
RECRUITING
Maplewood
Abbott-Northwestern Hospital
RECRUITING
Minneapolis
Hennepin County Medical Center
RECRUITING
Minneapolis
Coborn Cancer Center at Saint Cloud Hospital
RECRUITING
Saint Cloud
Park Nicollet Clinic - Saint Louis Park
RECRUITING
Saint Louis Park
Regions Hospital
RECRUITING
Saint Paul
United Hospital
RECRUITING
Saint Paul
Essentia Health Sandstone
RECRUITING
Sandstone
Essentia Health Virginia Clinic
RECRUITING
Virginia
Minnesota Oncology Hematology PA-Woodbury
RECRUITING
Woodbury
Missouri
Saint Francis Medical Center
RECRUITING
Cape Girardeau
Saint Luke's Hospital
RECRUITING
Chesterfield
Siteman Cancer Center at Saint Peters Hospital
RECRUITING
City Of Saint Peters
Siteman Cancer Center at West County Hospital
RECRUITING
Creve Coeur
University Health Truman Medical Center
RECRUITING
Kansas City
University of Kansas Cancer Center - North
RECRUITING
Kansas City
University of Kansas Cancer Center - Lee's Summit
RECRUITING
Lee's Summit
University of Kansas Cancer Center at North Kansas City Hospital
SUSPENDED
North Kansas City
CoxHealth South Hospital
RECRUITING
Springfield
Mercy Hospital Springfield
RECRUITING
Springfield
Mercy Hospital South
RECRUITING
St Louis
Siteman Cancer Center at Christian Hospital
RECRUITING
St Louis
Siteman Cancer Center-South County
RECRUITING
St Louis
Washington University School of Medicine
RECRUITING
St Louis
Montana
Community Hospital of Anaconda
RECRUITING
Anaconda
Billings Clinic Cancer Center
RECRUITING
Billings
Bozeman Health Deaconess Hospital
RECRUITING
Bozeman
Benefis Sletten Cancer Institute
RECRUITING
Great Falls
Logan Health Medical Center
RECRUITING
Kalispell
Community Medical Center
RECRUITING
Missoula
North Carolina
UNC Lineberger Comprehensive Cancer Center
RECRUITING
Chapel Hill
Duke University Medical Center
RECRUITING
Durham
North Dakota
Sanford Bismarck Medical Center
RECRUITING
Bismarck
Essentia Health Cancer Center-South University Clinic
RECRUITING
Fargo
Sanford Broadway Medical Center
RECRUITING
Fargo
Sanford Roger Maris Cancer Center
RECRUITING
Fargo
Nebraska
Nebraska Medicine-Bellevue
RECRUITING
Bellevue
Nebraska Medicine-Village Pointe
RECRUITING
Omaha
University of Nebraska Medical Center
RECRUITING
Omaha
New Hampshire
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
RECRUITING
Lebanon
New York
Roswell Park Cancer Institute
RECRUITING
Buffalo
Hematology Oncology Associates of CNY at Camillus
RECRUITING
Camillus
Hematology Oncology Associates of Central New York-East Syracuse
RECRUITING
East Syracuse
NYU Langone Hospital - Long Island
RECRUITING
Mineola
Laura and Isaac Perlmutter Cancer Center at NYU Langone
RECRUITING
New York
NYP/Weill Cornell Medical Center
RECRUITING
New York
University of Rochester
RECRUITING
Rochester
Wilmot Cancer Institute at Webster
RECRUITING
Webster
Ohio
Ohio State University Comprehensive Cancer Center
RECRUITING
Columbus
Oklahoma
Cancer Centers of Southwest Oklahoma Research
RECRUITING
Lawton
University of Oklahoma Health Sciences Center
RECRUITING
Oklahoma City
Oklahoma Cancer Specialists and Research Institute-Tulsa
RECRUITING
Tulsa
Oregon
Providence Newberg Medical Center
RECRUITING
Newberg
Saint Alphonsus Cancer Care Center-Ontario
RECRUITING
Ontario
Providence Willamette Falls Medical Center
RECRUITING
Oregon City
Providence Portland Medical Center
RECRUITING
Portland
Providence Saint Vincent Medical Center
RECRUITING
Portland
Rhode Island
Rhode Island Hospital
RECRUITING
Providence
Smilow Cancer Hospital Care Center - Westerly
RECRUITING
Westerly
South Carolina
Prisma Health Cancer Institute - Spartanburg
RECRUITING
Boiling Springs
Medical University of South Carolina
RECRUITING
Charleston
Prisma Health Cancer Institute - Easley
RECRUITING
Easley
Prisma Health Cancer Institute - Butternut
RECRUITING
Greenville
Prisma Health Cancer Institute - Eastside
RECRUITING
Greenville
Prisma Health Cancer Institute - Faris
RECRUITING
Greenville
Prisma Health Cancer Institute - Greer
RECRUITING
Greer
Prisma Health Cancer Institute - Seneca
RECRUITING
Seneca
South Dakota
Sanford Cancer Center Oncology Clinic
RECRUITING
Sioux Falls
Sanford USD Medical Center - Sioux Falls
RECRUITING
Sioux Falls
Utah
Huntsman Cancer Institute/University of Utah
RECRUITING
Salt Lake City
Virginia
VCU Massey Cancer Center at Stony Point
RECRUITING
Richmond
VCU Massey Comprehensive Cancer Center
RECRUITING
Richmond
Vermont
Dartmouth Cancer Center - North
RECRUITING
Saint Johnsbury
Washington
Swedish Cancer Institute-Edmonds
RECRUITING
Edmonds
Swedish Cancer Institute-Issaquah
RECRUITING
Issaquah
Swedish Medical Center-First Hill
RECRUITING
Seattle
Wisconsin
Duluth Clinic Ashland
RECRUITING
Ashland
Marshfield Medical Center-EC Cancer Center
RECRUITING
Eau Claire
University of Wisconsin Carbone Cancer Center - Johnson Creek
RECRUITING
Johnson Creek
Gundersen Lutheran Medical Center
RECRUITING
La Crosse
University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
RECRUITING
Madison
University of Wisconsin Carbone Cancer Center - University Hospital
RECRUITING
Madison
Marshfield Medical Center-Marshfield
RECRUITING
Marshfield
Medical College of Wisconsin
RECRUITING
Milwaukee
Marshfield Medical Center - Minocqua
RECRUITING
Minocqua
ProHealth D N Greenwald Center
RECRUITING
Mukwonago
Froedtert and MCW Moorland Reserve Health Center
RECRUITING
New Berlin
ProHealth Oconomowoc Memorial Hospital
RECRUITING
Oconomowoc
Marshfield Medical Center-Rice Lake
RECRUITING
Rice Lake
Marshfield Medical Center-River Region at Stevens Point
RECRUITING
Stevens Point
UW Cancer Center at ProHealth Care
RECRUITING
Waukesha
Marshfield Medical Center - Weston
RECRUITING
Weston
Contact Information
Primary
Anne Beaven, MD
anne_beaven@med.unc.edu
919-966-9268
Backup
Destin Carlisle
dcarlisle@bsd.uchicago.edu
773-702-8824
Time Frame
Start Date: 2023-10-20
Estimated Completion Date: 2038-08-31
Participants
Target number of participants: 421
Treatments
Experimental: Induction therapy (Zanubrutinib, rituximab)
Patients receive zanubrutinib PO and rituximab IV on study. Patients undergo bone marrow biopsy and FDG PET/CT or CT throughout the trial. Patients may also undergo EDG and/or colonoscopy on study as clinically indicated. Patients may optionally undergo blood sample collection throughout the trial.
Experimental: Arm A (Zanubrutinib)
Patients receive zanubrutinib PO until first disease progression on study. Patients undergo CT or MRI or FDG PET/CT throughout the trial. Patients may optionally undergo blood sample collection throughout the trial.
Active_comparator: ARM B (Observation)
Patients undergo observation until first disease progression and then receive zanubrutinib PO until second disease progression on study. Patients undergo CT or MRI or FDG PET/CT throughout the trial. Patients may optionally undergo blood sample collection throughout the trial.
Sponsors
Leads: Alliance for Clinical Trials in Oncology
Collaborators: National Cancer Institute (NCI)

This content was sourced from clinicaltrials.gov

Similar Clinical Trials