Actively Recruiting
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
Led by National Cancer Institute (NCI) · Updated on 2026-05-13
92
Participants Needed
125
Research Sites
325 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
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.
CONDITIONS
Official Title
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
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Diagnosis of Waldenstrom's macroglobulinemia or lymphoplasmacytic lymphoma with measurable disease by IgM protein (IgM spike 500 mg/dL)
- Baseline disease testing done within 28 days before registration
- At least one therapy requirement such as anemia, thrombocytopenia, neuropathy related to WM, symptomatic hyperviscosity, WM-related kidney disease, bulky disease, or constitutional symptoms
- No prior systemic therapy except rituximab if last dose was at least 6 months ago
- Age 18 years or older
- History and physical exam within 28 days before registration
- Zubrod performance status 0 to 2
- Adequate kidney function with creatinine clearance 30 mL/min within 14 days before registration
- Liver function within limits: bilirubin 1.5 x normal, AST and ALT 3 x normal, alkaline phosphatase 3 x normal within 14 days before registration
- Platelet count 50,000 cells/mm3 within 14 days before registration (transfusion allowed up to 7 days prior)
- Hemoglobin 7.0 g/dL within 14 days before registration (transfusion allowed up to 7 days prior)
- Absolute neutrophil count 1,000 cells/mm3 within 14 days before registration (transfusion allowed up to 7 days prior)
- Participants with HIV allowed if on effective therapy with undetectable viral load within 6 months
- Able to swallow oral medication and no gastrointestinal conditions affecting absorption
- Not intolerant to rituximab
- No active major infections
- Not seropositive for hepatitis C unless cured
- Avoid grapefruit, Seville oranges, or starfruit 3 days before venetoclax
- Not pregnant or nursing; effective contraception required for those of reproductive potential
- No other recent malignancies except specified treated or cured cancers
- Willingness to participate in specimen banking and sign informed consent
- Meet crossover criteria if applicable, including disease progression and adequate organ function
You will not qualify if you...
- Use of moderate or strong CYP3A or P-gp inhibitors or inducers within 7 days prior to first dose unless switched to safe alternative
- Known intolerance to rituximab
- Active bacterial, viral, fungal, mycobacterial, parasitic, or other infection at enrollment (except localized fungal infections)
- Hepatitis C seropositive without sustained virologic response
- Pregnant or nursing women
- History of other malignancies not meeting specified remission or cure criteria
- Transformation to intermediate or high-grade lymphoma or Bing-Neel syndrome preventing crossover
- Poor organ function or performance status outside inclusion criteria for crossover
- Platelet count, hemoglobin, or neutrophil count below required thresholds for crossover
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Trial Site Locations
Total: 125 locations
1
Banner University Medical Center - Tucson
Tucson, Arizona, United States, 85719
Actively Recruiting
2
University of Arizona Cancer Center-North Campus
Tucson, Arizona, United States, 85719
Actively Recruiting
3
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida, United States, 33146
Actively Recruiting
4
UM Sylvester Comprehensive Cancer Center at Coral Springs
Coral Springs, Florida, United States, 33065
Actively Recruiting
5
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, United States, 33442
Actively Recruiting
6
UM Sylvester Comprehensive Cancer Center at Doral
Doral, Florida, United States, 33166
Actively Recruiting
7
UM Sylvester Comprehensive Cancer Center at Hollywood
Hollywood, Florida, United States, 33021
Actively Recruiting
8
Mayo Clinic in Florida
Jacksonville, Florida, United States, 32224-9980
Actively Recruiting
9
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, United States, 33136
Actively Recruiting
10
UM Sylvester Comprehensive Cancer Center at Kendall
Miami, Florida, United States, 33176
Actively Recruiting
11
University of Miami Sylvester Comprehensive Cancer Center at Sole Mia
North Miami, Florida, United States, 33181
Actively Recruiting
12
UM Sylvester Comprehensive Cancer Center at Plantation
Plantation, Florida, United States, 33324
Actively Recruiting
13
Centralia Oncology Clinic
Centralia, Illinois, United States, 62801
Actively Recruiting
14
Carle at The Riverfront
Danville, Illinois, United States, 61832
Actively Recruiting
15
Cancer Care Specialists of Illinois - Decatur
Decatur, Illinois, United States, 62526
Actively Recruiting
16
Carle Physician Group-Effingham
Effingham, Illinois, United States, 62401
Actively Recruiting
17
Crossroads Cancer Center
Effingham, Illinois, United States, 62401
Actively Recruiting
18
Carle Physician Group-Mattoon/Charleston
Mattoon, Illinois, United States, 61938
Actively Recruiting
19
Cancer Care Center of O'Fallon
O'Fallon, Illinois, United States, 62269
Actively Recruiting
20
Southern Illinois University School of Medicine
Springfield, Illinois, United States, 62702
Actively Recruiting
21
Springfield Clinic
Springfield, Illinois, United States, 62702
Actively Recruiting
22
Springfield Memorial Hospital
Springfield, Illinois, United States, 62781
Actively Recruiting
23
Carle Cancer Center
Urbana, Illinois, United States, 61801
Actively Recruiting
24
Mary Greeley Medical Center
Ames, Iowa, United States, 50010
Actively Recruiting
25
McFarland Clinic - Ames
Ames, Iowa, United States, 50010
Actively Recruiting
26
McFarland Clinic - Boone
Boone, Iowa, United States, 50036
Suspended
27
McFarland Clinic - Trinity Cancer Center
Fort Dodge, Iowa, United States, 50501
Actively Recruiting
28
McFarland Clinic - Jefferson
Jefferson, Iowa, United States, 50129
Suspended
29
McFarland Clinic - Marshalltown
Marshalltown, Iowa, United States, 50158
Actively Recruiting
30
Trinity Health Saint Joseph Mercy Hospital Ann Arbor
Ann Arbor, Michigan, United States, 48106
Actively Recruiting
31
Trinity Health IHA Medical Group Hematology Oncology - Brighton
Brighton, Michigan, United States, 48114
Actively Recruiting
32
Trinity Health Medical Center - Brighton
Brighton, Michigan, United States, 48114
Actively Recruiting
33
Trinity Health IHA Medical Group Hematology Oncology - Canton
Canton, Michigan, United States, 48188
Actively Recruiting
34
Trinity Health Medical Center - Canton
Canton, Michigan, United States, 48188
Actively Recruiting
35
Chelsea Hospital
Chelsea, Michigan, United States, 48118
Actively Recruiting
36
Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
Chelsea, Michigan, United States, 48118
Actively Recruiting
37
Hematology Oncology Consultants-Clarkston
Clarkston, Michigan, United States, 48346
Actively Recruiting
38
Newland Medical Associates-Clarkston
Clarkston, Michigan, United States, 48346
Actively Recruiting
39
Henry Ford Macomb Hospital-Clinton Township
Clinton Township, Michigan, United States, 48038
Actively Recruiting
40
Henry Ford Hospital
Detroit, Michigan, United States, 48202
Actively Recruiting
41
Cancer Hematology Centers - Flint
Flint, Michigan, United States, 48503
Actively Recruiting
42
Genesee Hematology Oncology PC
Flint, Michigan, United States, 48503
Suspended
43
Genesys Hurley Cancer Institute
Flint, Michigan, United States, 48503
Actively Recruiting
44
Hurley Medical Center
Flint, Michigan, United States, 48503
Actively Recruiting
45
University of Michigan Health - Sparrow Lansing
Lansing, Michigan, United States, 48912
Actively Recruiting
46
Trinity Health Saint Mary Mercy Livonia Hospital
Livonia, Michigan, United States, 48154
Actively Recruiting
47
Henry Ford Medical Center-Columbus
Novi, Michigan, United States, 48377
Actively Recruiting
48
Michigan Healthcare Professionals Pontiac
Pontiac, Michigan, United States, 48341
Actively Recruiting
49
Newland Medical Associates-Pontiac
Pontiac, Michigan, United States, 48341
Actively Recruiting
50
Trinity Health Saint Joseph Mercy Oakland Hospital
Pontiac, Michigan, United States, 48341
Actively Recruiting
51
MyMichigan Medical Center Saginaw
Saginaw, Michigan, United States, 48601
Actively Recruiting
52
Oncology Hematology Associates of Saginaw Valley PC
Saginaw, Michigan, United States, 48604
Suspended
53
MyMichigan Medical Center Tawas
Tawas City, Michigan, United States, 48764
Actively Recruiting
54
Henry Ford West Bloomfield Hospital
West Bloomfield, Michigan, United States, 48322
Actively Recruiting
55
Huron Gastroenterology PC
Ypsilanti, Michigan, United States, 48106
Actively Recruiting
56
Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
Ypsilanti, Michigan, United States, 48197
Actively Recruiting
57
Mayo Clinic in Rochester
Rochester, Minnesota, United States, 55905
Actively Recruiting
58
Saint Francis Medical Center
Cape Girardeau, Missouri, United States, 63703
Actively Recruiting
59
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, United States, 63376
Active, Not Recruiting
60
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, United States, 63141
Active, Not Recruiting
61
Heartland Regional Medical Center
Saint Joseph, Missouri, United States, 64506
Actively Recruiting
62
Washington University School of Medicine
St Louis, Missouri, United States, 63110
Active, Not Recruiting
63
Mercy Hospital South
St Louis, Missouri, United States, 63128
Actively Recruiting
64
Siteman Cancer Center-South County
St Louis, Missouri, United States, 63129
Active, Not Recruiting
65
Siteman Cancer Center at Christian Hospital
St Louis, Missouri, United States, 63136
Active, Not Recruiting
66
Saint Vincent Frontier Cancer Center
Billings, Montana, United States, 59102
Actively Recruiting
67
Memorial Sloan Kettering Basking Ridge
Basking Ridge, New Jersey, United States, 07920
Actively Recruiting
68
Memorial Sloan Kettering Monmouth
Middletown, New Jersey, United States, 07748
Actively Recruiting
69
Memorial Sloan Kettering Bergen
Montvale, New Jersey, United States, 07645
Actively Recruiting
70
Memorial Sloan Kettering Commack
Commack, New York, United States, 11725
Actively Recruiting
71
Glens Falls Hospital
Glens Falls, New York, United States, 12801
Active, Not Recruiting
72
Memorial Sloan Kettering Westchester
Harrison, New York, United States, 10604
Actively Recruiting
73
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, United States, 10032
Active, Not Recruiting
74
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Actively Recruiting
75
University of Rochester
Rochester, New York, United States, 14642
Actively Recruiting
76
Memorial Sloan Kettering Nassau
Uniondale, New York, United States, 11553
Actively Recruiting
77
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, United States, 28203
Actively Recruiting
78
Southeastern Medical Oncology Center-Clinton
Clinton, North Carolina, United States, 28328
Actively Recruiting
79
Levine Cancer Institute-Gaston
Gastonia, North Carolina, United States, 28054
Actively Recruiting
80
Southeastern Medical Oncology Center-Goldsboro
Goldsboro, North Carolina, United States, 27534
Actively Recruiting
81
Southeastern Medical Oncology Center-Jacksonville
Jacksonville, North Carolina, United States, 28546
Actively Recruiting
82
Strecker Cancer Center-Belpre
Belpre, Ohio, United States, 45714
Suspended
83
Adena Regional Medical Center
Chillicothe, Ohio, United States, 45601
Suspended
84
Mount Carmel East Hospital
Columbus, Ohio, United States, 43213
Suspended
85
Columbus Oncology and Hematology Associates Inc
Columbus, Ohio, United States, 43214
Suspended
86
Riverside Methodist Hospital
Columbus, Ohio, United States, 43214
Suspended
87
Grant Medical Center
Columbus, Ohio, United States, 43215
Suspended
88
The Mark H Zangmeister Center
Columbus, Ohio, United States, 43219
Suspended
89
Mount Carmel Health Center West
Columbus, Ohio, United States, 43222
Suspended
90
Doctors Hospital
Columbus, Ohio, United States, 43228
Suspended
91
Delaware Health Center-Grady Cancer Center
Delaware, Ohio, United States, 43015
Suspended
92
Grady Memorial Hospital
Delaware, Ohio, United States, 43015
Suspended
93
Dublin Methodist Hospital
Dublin, Ohio, United States, 43016
Suspended
94
Central Ohio Breast and Endocrine Surgery
Gahanna, Ohio, United States, 43230
Suspended
95
Mount Carmel Grove City Hospital
Grove City, Ohio, United States, 43123
Suspended
96
Fairfield Medical Center
Lancaster, Ohio, United States, 43130
Suspended
97
Saint Rita's Medical Center
Lima, Ohio, United States, 45801
Suspended
98
OhioHealth Mansfield Hospital
Mansfield, Ohio, United States, 44903
Suspended
99
Marietta Memorial Hospital
Marietta, Ohio, United States, 45750
Suspended
100
OhioHealth Marion General Hospital
Marion, Ohio, United States, 43302
Suspended
101
Knox Community Hospital
Mount Vernon, Ohio, United States, 43050
Suspended
102
Licking Memorial Hospital
Newark, Ohio, United States, 43055
Actively Recruiting
103
Newark Radiation Oncology
Newark, Ohio, United States, 43055
Suspended
104
Mercy Health - Perrysburg Hospital
Perrysburg, Ohio, United States, 43551
Suspended
105
Southern Ohio Medical Center
Portsmouth, Ohio, United States, 45662
Suspended
106
Mercy Health - Saint Vincent Hospital
Toledo, Ohio, United States, 43608
Suspended
107
Mercy Health - Saint Anne Hospital
Toledo, Ohio, United States, 43623
Suspended
108
Saint Ann's Hospital
Westerville, Ohio, United States, 43081
Suspended
109
Genesis Healthcare System Cancer Care Center
Zanesville, Ohio, United States, 43701
Suspended
110
Providence Cancer Institute Clackamas Clinic
Clackamas, Oregon, United States, 97015
Suspended
111
Providence Newberg Medical Center
Newberg, Oregon, United States, 97132
Actively Recruiting
112
Providence Willamette Falls Medical Center
Oregon City, Oregon, United States, 97045
Actively Recruiting
113
Providence Portland Medical Center
Portland, Oregon, United States, 97213
Actively Recruiting
114
Providence Saint Vincent Medical Center
Portland, Oregon, United States, 97225
Actively Recruiting
115
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, United States, 23298
Actively Recruiting
116
Swedish Cancer Institute-Edmonds
Edmonds, Washington, United States, 98026
Actively Recruiting
117
Swedish Cancer Institute-Issaquah
Issaquah, Washington, United States, 98029
Actively Recruiting
118
Swedish Medical Center-First Hill
Seattle, Washington, United States, 98122
Actively Recruiting
119
Marshfield Medical Center-EC Cancer Center
Eau Claire, Wisconsin, United States, 54701
Active, Not Recruiting
120
Gundersen Lutheran Medical Center
La Crosse, Wisconsin, United States, 54601
Actively Recruiting
121
Marshfield Medical Center-Marshfield
Marshfield, Wisconsin, United States, 54449
Active, Not Recruiting
122
Marshfield Medical Center - Minocqua
Minocqua, Wisconsin, United States, 54548
Active, Not Recruiting
123
Marshfield Medical Center-Rice Lake
Rice Lake, Wisconsin, United States, 54868
Active, Not Recruiting
124
Marshfield Medical Center-River Region at Stevens Point
Stevens Point, Wisconsin, United States, 54482
Active, Not Recruiting
125
Marshfield Medical Center - Weston
Weston, Wisconsin, United States, 54476
Active, Not Recruiting
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
RANDOMIZED
Model
CROSSOVER
Primary Purpose
TREATMENT
Number of Arms
2
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