Testing the Combination of Venetoclax and Rituximab, in Comparison to the Usual Treatment (Ibrutinib Plus Rituximab or Zanubrutinib Alone) for Waldenstrom's Macroglobulinemia/Lymphoplasmacytic Lymphoma
Start Date
1/5/2022
Completion Date
3/31/2028
Summary
This phase II trial studies the effects of venetoclax and rituximab in comparison to ibrutinib and rituximab or zanubrutinib in treating patients with previously untreated Waldenstrom's macroglobulinemia/lymphoplasmacytic lymphoma. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. 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. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Zanubrutinib, a type of tyrosine kinase inhibitor, blocks a protein called BTK, which may help keep cancer cells from growing. Giving venetoclax and rituximab may work better in treating patients with previously untreated Waldenstrom's macroglobulinemia than ibrutinib with rituximab or zanubrutinib alone.
Detailed Description
PRIMARY OBJECTIVE: I. To compare the rate of very good partial response or better (VGPR or better) in previously untreated participants with Waldenström's macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) who are treated upfront with ibrutinib + rituximab (IR) or zanubrutinib alone (Z) versus (vs.) venetoclax +/- rituximab (VR) regimen. SECONDARY OBJECTIVES: I. To compare overall response rates (ORR) in WM participants treated upfront with ibrutinib + rituximab or zanubrutinib alone vs. venetoclax + rituximab. II. To compare progression-free survival (PFS), time to next treatment, duration of response in WM participants treated upfront with ibrutinib + rituximab or zanubrutinib alone vs. venetoclax + rituximab. III. To compare the rate of complete response (CR) in WM participants treated upfront with ibrutinib + rituximab or zanubrutinib alone vs. venetoclax + rituximab. IV. To evaluate the safety of ibrutinib + rituximab or zanubrutinib alone vs. venetoclax + rituximab in participants with WM. V. To evaluate the time to VGPR in WM participants treated upfront with ibrutinib + rituximab or zanubrutinib alone vs. venetoclax + rituximab. VI. To evaluate the ORR in participants who progress on treatment with ibrutinib + rituximab or zanubrutinib alone and venetoclax + rituximab are crossed over to the other respective arm. VII. To compare overall survival (OS) in WM participants treated upfront with ibrutinib + rituximab or zanubrutinib alone vs. venetoclax + rituximab. VIII. To evaluate the rate of VGPR or better and the ORR in WM participants treated upfront with ibrutinib plus rituximab vs. those treated with zanubrutinib alone. BANKING OBJECTIVE: I. To bank specimens for future correlative studies. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive ibrutinib orally (PO) once daily (QD) on days 1-28 of cycles 1-24 and rituximab intravenously (IV) on days 1, 8, 15, and 22 of cycles 2 and 5, or zanubrutinib PO QD or twice daily (BID) on days 1-28 of cycles 1-24. Cycles repeat every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Patients with progressive disease during Arm I may receive rituximab and venetoclax as in Arm II for up to an additional 24 cycles. Patients undergo computed tomography (CT) or positron emission tomography (PET)/CT and bone marrow biopsy and aspiration as well as blood sample collection throughout the trial. ARM II: Patients receive venetoclax PO QD on days 1-28 of each cycle and rituximab IV on days 1, 8, 15, and 22 of cycles 2 and 5. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Patients with progressive disease during Arm II may receive ibrutinib and rituximab as in Arm I for up to an additional 24 cycles. Patients undergo CT or PET/CT and bone marrow biopsy and aspiration as well as blood sample collection throughout the trial. After completion of study treatment, patients removed from protocol prior to progression are followed every 3 months until progression, death or 5 years after initial registration, whichever occurs first. Patients followed after progression of disease are followed every 6 months until death or 5 years after initial registration.
Eligibility Criteria
Age Range: 18 years to No maximum
Interventions
Biospecimen Collection
Bone Marrow Aspiration
Bone Marrow Biopsy
Computed Tomography
Ibrutinib
Positron Emission Tomography
Rituximab
Venetoclax
Zanubrutinib
Conditions
Locations
Banner University Medical Center - Tucson
Tucson, Arizona 85719
United States
University of Arizona Cancer Center-North Campus
Tucson, Arizona 85719
United States
City of Hope at Irvine Lennar
Irvine, California 92618
United States
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida 33146
United States
UM Sylvester Comprehensive Cancer Center at Coral Springs
Coral Springs, Florida 33065
United States
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida 33442
United States
UM Sylvester Comprehensive Cancer Center at Doral
Doral, Florida 33166
United States
UM Sylvester Comprehensive Cancer Center at Hollywood
Hollywood, Florida 33021
United States
Mayo Clinic in Florida
Jacksonville, Florida 32224-9980
United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida 33136
United States
UM Sylvester Comprehensive Cancer Center at Kendall
Miami, Florida 33176
United States
University of Miami Sylvester Comprehensive Cancer Center at Sole Mia
North Miami, Florida 33181
United States
UM Sylvester Comprehensive Cancer Center at Plantation
Plantation, Florida 33324
United States
Saint Alphonsus Cancer Care Center-Nampa
Nampa, Idaho 83687
United States
Centralia Oncology Clinic
Centralia, Illinois 62801
United States
Carle at The Riverfront
Danville, Illinois 61832
United States
Cancer Care Specialists of Illinois - Decatur
Decatur, Illinois 62526
United States
Carle Physician Group-Effingham
Effingham, Illinois 62401
United States
Crossroads Cancer Center
Effingham, Illinois 62401
United States
Carle Physician Group-Mattoon/Charleston
Mattoon, Illinois 61938
United States
Loyola University Medical Center
Maywood, Illinois 60153
United States
Cancer Care Center of O'Fallon
O'Fallon, Illinois 62269
United States
Southern Illinois University School of Medicine
Springfield, Illinois 62702
United States
Springfield Clinic
Springfield, Illinois 62702
United States
Springfield Memorial Hospital
Springfield, Illinois 62781
United States
Carle Cancer Center
Urbana, Illinois 61801
United States
Mary Greeley Medical Center
Ames, Iowa 50010
United States
McFarland Clinic - Ames
Ames, Iowa 50010
United States
McFarland Clinic - Boone
Boone, Iowa 50036
United States
McFarland Clinic - Trinity Cancer Center
Fort Dodge, Iowa 50501
United States
McFarland Clinic - Jefferson
Jefferson, Iowa 50129
United States
McFarland Clinic - Marshalltown
Marshalltown, Iowa 50158
United States
Trinity Health Saint Joseph Mercy Hospital Ann Arbor
Ann Arbor, Michigan 48106
United States
Trinity Health IHA Medical Group Hematology Oncology - Brighton
Brighton, Michigan 48114
United States
Trinity Health Medical Center - Brighton
Brighton, Michigan 48114
United States
Trinity Health IHA Medical Group Hematology Oncology - Canton
Canton, Michigan 48188
United States
Trinity Health Medical Center - Canton
Canton, Michigan 48188
United States
Chelsea Hospital
Chelsea, Michigan 48118
United States
Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
Chelsea, Michigan 48118
United States
Hematology Oncology Consultants-Clarkston
Clarkston, Michigan 48346
United States
Newland Medical Associates-Clarkston
Clarkston, Michigan 48346
United States
Henry Ford Macomb Hospital-Clinton Township
Clinton Township, Michigan 48038
United States
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan 48201
United States
Henry Ford Hospital
Detroit, Michigan 48202
United States
Weisberg Cancer Treatment Center
Farmington Hills, Michigan 48334
United States
Cancer Hematology Centers - Flint
Flint, Michigan 48503
United States
Genesee Hematology Oncology PC
Flint, Michigan 48503
United States
Genesys Hurley Cancer Institute
Flint, Michigan 48503
United States
Hurley Medical Center
Flint, Michigan 48503
United States
University of Michigan Health - Sparrow Lansing
Lansing, Michigan 48912
United States
Trinity Health Saint Mary Mercy Livonia Hospital
Livonia, Michigan 48154
United States
Henry Ford Medical Center-Columbus
Novi, Michigan 48377
United States
Michigan Healthcare Professionals Pontiac
Pontiac, Michigan 48341
United States
Newland Medical Associates-Pontiac
Pontiac, Michigan 48341
United States
Trinity Health Saint Joseph Mercy Oakland Hospital
Pontiac, Michigan 48341
United States
MyMichigan Medical Center Saginaw
Saginaw, Michigan 48601
United States
Oncology Hematology Associates of Saginaw Valley PC
Saginaw, Michigan 48604
United States
MyMichigan Medical Center Tawas
Tawas City, Michigan 48764
United States
Henry Ford West Bloomfield Hospital
West Bloomfield, Michigan 48322
United States
Huron Gastroenterology PC
Ypsilanti, Michigan 48106
United States
Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
Ypsilanti, Michigan 48197
United States
Mercy Hospital
Coon Rapids, Minnesota 55433
United States
Abbott-Northwestern Hospital
Minneapolis, Minnesota 55407
United States
Hennepin County Medical Center
Minneapolis, Minnesota 55415
United States
Mayo Clinic in Rochester
Rochester, Minnesota 55905
United States
Park Nicollet Clinic - Saint Louis Park
Saint Louis Park, Minnesota 55416
United States
Regions Hospital
Saint Paul, Minnesota 55101
United States
United Hospital
Saint Paul, Minnesota 55102
United States
Saint Francis Medical Center
Cape Girardeau, Missouri 63703
United States
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri 63376
United States
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri 63141
United States
Heartland Regional Medical Center
Saint Joseph, Missouri 64506
United States
Washington University School of Medicine
St Louis, Missouri 63110
United States
Mercy Hospital South
St Louis, Missouri 63128
United States
Siteman Cancer Center-South County
St Louis, Missouri 63129
United States
Siteman Cancer Center at Christian Hospital
St Louis, Missouri 63136
United States
Saint Vincent Frontier Cancer Center
Billings, Montana 59102
United States
Memorial Sloan Kettering Basking Ridge
Basking Ridge, New Jersey 07920
United States
Memorial Sloan Kettering Monmouth
Middletown, New Jersey 07748
United States
Memorial Sloan Kettering Bergen
Montvale, New Jersey 07645
United States
Memorial Sloan Kettering Commack
Commack, New York 11725
United States
Glens Falls Hospital
Glens Falls, New York 12801
United States
Memorial Sloan Kettering Westchester
Harrison, New York 10604
United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York 10032
United States
Memorial Sloan Kettering Cancer Center
New York, New York 10065
United States
University of Rochester
Rochester, New York 14642
United States
Memorial Sloan Kettering Nassau
Uniondale, New York 11553
United States
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina 28203
United States
Southeastern Medical Oncology Center-Clinton
Clinton, North Carolina 28328
United States
Levine Cancer Institute-Gaston
Gastonia, North Carolina 28054
United States
Southeastern Medical Oncology Center-Goldsboro
Goldsboro, North Carolina 27534
United States
Southeastern Medical Oncology Center-Jacksonville
Jacksonville, North Carolina 28546
United States
Atrium Health Union/LCI-Union
Monroe, North Carolina 28112
United States
Strecker Cancer Center-Belpre
Belpre, Ohio 45714
United States
Adena Regional Medical Center
Chillicothe, Ohio 45601
United States
Mount Carmel East Hospital
Columbus, Ohio 43213
United States
Columbus Oncology and Hematology Associates Inc
Columbus, Ohio 43214
United States
Riverside Methodist Hospital
Columbus, Ohio 43214
United States
Grant Medical Center
Columbus, Ohio 43215
United States
The Mark H Zangmeister Center
Columbus, Ohio 43219
United States
Mount Carmel Health Center West
Columbus, Ohio 43222
United States
Doctors Hospital
Columbus, Ohio 43228
United States
Delaware Health Center-Grady Cancer Center
Delaware, Ohio 43015
United States
Grady Memorial Hospital
Delaware, Ohio 43015
United States
Dublin Methodist Hospital
Dublin, Ohio 43016
United States
Central Ohio Breast and Endocrine Surgery
Gahanna, Ohio 43230
United States
Mount Carmel Grove City Hospital
Grove City, Ohio 43123
United States
Fairfield Medical Center
Lancaster, Ohio 43130
United States
Saint Rita's Medical Center
Lima, Ohio 45801
United States
OhioHealth Mansfield Hospital
Mansfield, Ohio 44903
United States
Marietta Memorial Hospital
Marietta, Ohio 45750
United States
OhioHealth Marion General Hospital
Marion, Ohio 43302
United States
Knox Community Hospital
Mount Vernon, Ohio 43050
United States
Licking Memorial Hospital
Newark, Ohio 43055
United States
Newark Radiation Oncology
Newark, Ohio 43055
United States
Mercy Health - Perrysburg Hospital
Perrysburg, Ohio 43551
United States
Southern Ohio Medical Center
Portsmouth, Ohio 45662
United States
Mercy Health - Saint Vincent Hospital
Toledo, Ohio 43608
United States
Mercy Health - Saint Anne Hospital
Toledo, Ohio 43623
United States
Saint Ann's Hospital
Westerville, Ohio 43081
United States
Genesis Healthcare System Cancer Care Center
Zanesville, Ohio 43701
United States
Providence Cancer Institute Clackamas Clinic
Clackamas, Oregon 97015
United States
Providence Newberg Medical Center
Newberg, Oregon 97132
United States
Providence Willamette Falls Medical Center
Oregon City, Oregon 97045
United States
Providence Portland Medical Center
Portland, Oregon 97213
United States
Providence Saint Vincent Medical Center
Portland, Oregon 97225
United States
VCU Massey Comprehensive Cancer Center
Richmond, Virginia 23298
United States
Swedish Cancer Institute-Edmonds
Edmonds, Washington 98026
United States
Swedish Cancer Institute-Issaquah
Issaquah, Washington 98029
United States
Swedish Medical Center-First Hill
Seattle, Washington 98122
United States
ThedaCare Regional Cancer Center
Appleton, Wisconsin 54911
United States
Marshfield Medical Center-EC Cancer Center
Eau Claire, Wisconsin 54701
United States
Gundersen Lutheran Medical Center
La Crosse, Wisconsin 54601
United States
Marshfield Medical Center-Marshfield
Marshfield, Wisconsin 54449
United States
Marshfield Medical Center - Minocqua
Minocqua, Wisconsin 54548
United States
Marshfield Medical Center-Rice Lake
Rice Lake, Wisconsin 54868
United States
Marshfield Medical Center-River Region at Stevens Point
Stevens Point, Wisconsin 54482
United States
Marshfield Medical Center - Weston
Weston, Wisconsin 54476
United States