Testing the Combination of Venetoclax and Rituximab, in Comparison to the Usual Treatment (Ibrutinib and Rituximab) for Waldenstrom's Macroglobulinemia/Lymphoplasmacytic Lymphoma
NCT ID: NCT04840602
Last Updated: 2025-12-29
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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SUSPENDED
PHASE2
92 participants
INTERVENTIONAL
2022-01-05
2028-03-31
Brief Summary
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Detailed Description
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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 plus rituximab (IR) versus (vs.) venetoclax plus rituximab (VR) regimen.
SECONDARY OBJECTIVES:
I. To compare overall response rates (ORR) in WM participants treated upfront with IR vs. those treated with VR.
II. To compare progression-free survival (PFS), time to next treatment, duration of response in WM participants treated upfront with IR vs. those treated with VR.
III. To compare the rate of complete response (CR) in WM participants treated upfront with IR vs. those treated with VR.
IV. To evaluate the safety of the IR regimen as compared to VR regimen in participants with WM.
V. To evaluate the time to VGPR in WM participants treated upfront with IR and those treated with VR.
VI. To evaluate the ORR in participants who progress on treatment with IR and VR and are crossed over to the other respective arm.
VII. To compare overall survival (OS) in WM participants treated upfront with IR vs. those treated with VR.
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. 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.
Conditions
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Study Design
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RANDOMIZED
CROSSOVER
TREATMENT
NONE
Study Groups
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Arm I (ibrutinib, rituximab)
Patients receive ibrutinib PO QD on days 1-28 of cycles 1-24 and rituximab IV on days 1, 8, 15, and 22 of cycles 2 and 5. 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 CT or PET/CT and bone marrow biopsy and aspiration as well as blood sample collection throughout the trial.
Biospecimen Collection
Undergo blood sample collection
Bone Marrow Aspiration
Undergo bone marrow biopsy and aspiration
Bone Marrow Biopsy
Undergo bone marrow biopsy and aspiration
Computed Tomography
Undergo CT or PET/CT
Ibrutinib
Given PO
Positron Emission Tomography
Undergo PET/CT
Rituximab
Given IV
Arm II (venetoclax, rituximab)
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. 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 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.
Biospecimen Collection
Undergo blood sample collection
Bone Marrow Aspiration
Undergo bone marrow biopsy and aspiration
Bone Marrow Biopsy
Undergo bone marrow biopsy and aspiration
Computed Tomography
Undergo CT or PET/CT
Positron Emission Tomography
Undergo PET/CT
Rituximab
Given IV
Venetoclax
Given PO
Interventions
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Biospecimen Collection
Undergo blood sample collection
Bone Marrow Aspiration
Undergo bone marrow biopsy and aspiration
Bone Marrow Biopsy
Undergo bone marrow biopsy and aspiration
Computed Tomography
Undergo CT or PET/CT
Ibrutinib
Given PO
Positron Emission Tomography
Undergo PET/CT
Rituximab
Given IV
Venetoclax
Given PO
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* IgM Spike: ≥ 500 mg/dL (≥ 5 g/L)
* Extramedullary disease: The manifestation of a lymphoid mass outside of the bone marrow, resulting in enlargement in extramedullary organs such as the lymph nodes or spleen. Note: all participants must have measurable IgM spike, but are not required to have extramedullary disease
* Testing to establish baseline disease status must be performed within 28 days prior to registration
* Participants must have at least one of the criteria to require therapy for WM including anemia, thrombocytopenia, neuropathy related to WM, symptomatic hyperviscosity or serum viscosity levels greater than 4.0 centipoises, WM associated glomerulonephritis or renal disease, bulky disease, or constitutional symptoms. Constitutional symptoms can be described as unintentional weight loss \>= 10% within the previous 6 months prior to screening; Fevers higher than 100.5 degrees Fahrenheit (F) or 38.0 degrees Celsius (C) for 2 or more weeks prior to screening without evidence of infection; Night sweats for more than 1 month prior to screening without evidence of infection; Clinically relevant fatigue which is not relieved by rest due to WM
* Participants who require ongoing use or received a moderate or strong CYP3A inducer, moderate or strong CYP3A inhibitor, P-gp inhibitor within 7 days prior to the first dose of study drug will be excluded from the study. If such participants can be safely switched to an alternative agent, then the participants will be eligible to enroll
* Participants must not have had prior systemic therapy. Prior therapy with rituximab will be allowed as long as the last rituximab dose was at least 6 months prior to registration
* Participants must be \>= 18 years of age
* Participants must have history and physical exam within 28 days prior to registration
* Participants must have Zubrod performance status =\< 2
* Participants must have evidence of adequate renal function, as defined by creatinine clearance (CrCl) \>= 30 mL/min. Values must be obtained within 14 days prior to registration
* Total bilirubin =\< 1.5 x IULN (institutional upper limit of the norm) (within 14 days prior to registration)
* Aspartate aminotransferase (AST), alanine aminotransferase (ALT) =\< 3 x IULN (within 14 days prior to registration)
* Alkaline phosphatase =\< 3 x IULN (within 14 days prior to registration)
* Platelet count \>= 50,000 cells/mm\^3 (within 14 days prior to registration)
* NOTE: Transfusion and/or growth factor support is allowed up to 7 days prior to registration
* Hemoglobin \>= 7.5 g/dL (within 14 days prior to registration)
* NOTE: Transfusion and/or growth factor support is allowed up to 7 days prior to registration
* Absolute neutrophil count (ANC) \>= 1,000 cells/mm\^3 (within 14 days prior to registration)
* NOTE: Transfusion and/or growth factor support is allowed up to 7 days prior to registration
* Participants with known human immunodeficiency virus (HIV)-infection are eligible providing they are on effective anti-retroviral therapy and have undetectable viral load at their most recent viral load test and within 6 months prior to registration
* Participants must be able to take and swallow oral medication (capsules) whole. Participants may not have any known impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of the study drug (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
* Participants must not be intolerant to rituximab
* Participants must not have known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding localized skin and nail bed fungal infections) at study enrollment, or any major episode of infection requiring treatment with IV antibiotics or hospitalization (relating to the completion of the course of antibiotics) 4 weeks prior to registration
* Participants must not be seropositive for hepatitis C (except in the setting of sustained virologic response, defined as undetectable viral load at least 12 weeks after completion of antiviral therapy). Hepatitis C virus (HCV) testing is only required if clinically indicated or if the participant has a history of HCV
* Participants must not consume grapefruit, Seville oranges or starfruit within 3 days prior to the first dose of venetoclax
* Participants must not be pregnant or nursing because venetoclax has not been studied in pregnant or nursing women and the mechanism of action is expected to cause fetal harm. A woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months. In addition to routine contraceptive methods, "effective contraception" e.g., implants, injectables, combined oral contraceptives, some intrauterine devices \[IUDs\], complete abstinence, or sterilized partner) and a barrier method (e.g., condom, cervical ring, sponge, etc.). This also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation. However, if at any point a previously celibate participant chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures throughout the study and for at least 30 days after competition of therapy
* No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the participant is currently in complete remission, or any other cancer from which the participant has been disease free for two years or watchful waiting is appropriate in the opinion of the treating physician. Also, malignancy that in the opinion of the investigator, is considered cured with minimal risk of recurrence within 5 years, is permissible consideration of eligibility for this trial
* Participants must be offered the opportunity to participate in specimen banking
* Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines. For participants with impaired decision-making capabilities, legally authorized representatives may sign and give informed consent on behalf of study participants in accordance with applicable federal, local, and Central Institutional Review Board (CIRB) regulations
* As a part of the Oncology Participant Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
* CROSSOVER CRITERIA: Participants must have been registered and received treatment in the IR or VR arm and must show progression of disease at any time during cycles 3-24
* CROSSOVER CRITERIA: In case of transformation to intermediate or high-grade lymphoma or development of Bing-Neel syndrome the participants will not undergo registration step 2 crossover and will be taken off the study
* CROSSOVER CRITERIA: Participants must have Zubrod performance status =\< 2
* CROSSOVER CRITERIA: Participants must have evidence of adequate renal function, as defined by creatinine clearance (CrCl) \>= 30 mL/min. Values must be obtained within 14 days prior to registration
* CROSSOVER CRITERIA: Participants must have no evidence of marked hepatic dysfunction on any recent liver function tests within 14 days prior to registration
* CROSSOVER CRITERIA: Platelet count \>= 50,000 cells/mm\^3 (without within 14 days prior to registration)
* NOTE: Transfusion and/or growth factor support is allowed up to 7 days prior to registration
* CROSSOVER CRITERIA: Hemoglobin \>= 7.5 g/dL (without within 14 days prior to registration)
* NOTE: Transfusion and/or growth factor support is allowed up to 7 days prior to registration
* CROSSOVER CRITERIA: Absolute neutrophil count (ANC) \>= 1,000 cells/mm\^3 (without within 14 days prior to registration)
* NOTE: Transfusion and/or growth factor support is allowed up to 7 days prior to registration
18 Years
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
Responsible Party
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Principal Investigators
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Sikander Ailawadhi
Role: PRINCIPAL_INVESTIGATOR
SWOG Cancer Research Network
Locations
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Banner University Medical Center - Tucson
Tucson, Arizona, United States
University of Arizona Cancer Center-North Campus
Tucson, Arizona, United States
Mayo Clinic in Florida
Jacksonville, Florida, United States
Centralia Oncology Clinic
Centralia, Illinois, United States
Carle at The Riverfront
Danville, Illinois, United States
Cancer Care Specialists of Illinois - Decatur
Decatur, Illinois, United States
Carle Physician Group-Effingham
Effingham, Illinois, United States
Crossroads Cancer Center
Effingham, Illinois, United States
Carle Physician Group-Mattoon/Charleston
Mattoon, Illinois, United States
Cancer Care Center of O'Fallon
O'Fallon, Illinois, United States
Southern Illinois University School of Medicine
Springfield, Illinois, United States
Springfield Clinic
Springfield, Illinois, United States
Springfield Memorial Hospital
Springfield, Illinois, United States
Carle Cancer Center
Urbana, Illinois, United States
Mary Greeley Medical Center
Ames, Iowa, United States
McFarland Clinic - Ames
Ames, Iowa, United States
McFarland Clinic - Boone
Boone, Iowa, United States
McFarland Clinic - Trinity Cancer Center
Fort Dodge, Iowa, United States
McFarland Clinic - Jefferson
Jefferson, Iowa, United States
McFarland Clinic - Marshalltown
Marshalltown, Iowa, United States
Trinity Health Saint Joseph Mercy Hospital Ann Arbor
Ann Arbor, Michigan, United States
Trinity Health IHA Medical Group Hematology Oncology - Brighton
Brighton, Michigan, United States
Trinity Health Medical Center - Brighton
Brighton, Michigan, United States
Trinity Health IHA Medical Group Hematology Oncology - Canton
Canton, Michigan, United States
Trinity Health Medical Center - Canton
Canton, Michigan, United States
Chelsea Hospital
Chelsea, Michigan, United States
Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
Chelsea, Michigan, United States
Hematology Oncology Consultants-Clarkston
Clarkston, Michigan, United States
Newland Medical Associates-Clarkston
Clarkston, Michigan, United States
Henry Ford Hospital
Detroit, Michigan, United States
Cancer Hematology Centers - Flint
Flint, Michigan, United States
Genesee Hematology Oncology PC
Flint, Michigan, United States
Genesys Hurley Cancer Institute
Flint, Michigan, United States
Hurley Medical Center
Flint, Michigan, United States
University of Michigan Health - Sparrow Lansing
Lansing, Michigan, United States
Trinity Health Saint Mary Mercy Livonia Hospital
Livonia, Michigan, United States
Michigan Healthcare Professionals Pontiac
Pontiac, Michigan, United States
Newland Medical Associates-Pontiac
Pontiac, Michigan, United States
Trinity Health Saint Joseph Mercy Oakland Hospital
Pontiac, Michigan, United States
MyMichigan Medical Center Saginaw
Saginaw, Michigan, United States
Oncology Hematology Associates of Saginaw Valley PC
Saginaw, Michigan, United States
MyMichigan Medical Center Tawas
Tawas City, Michigan, United States
Huron Gastroenterology PC
Ypsilanti, Michigan, United States
Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
Ypsilanti, Michigan, United States
Mayo Clinic in Rochester
Rochester, Minnesota, United States
Saint Francis Medical Center
Cape Girardeau, Missouri, United States
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, United States
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, United States
Heartland Regional Medical Center
Saint Joseph, Missouri, United States
Washington University School of Medicine
St Louis, Missouri, United States
Mercy Hospital South
St Louis, Missouri, United States
Siteman Cancer Center-South County
St Louis, Missouri, United States
Siteman Cancer Center at Christian Hospital
St Louis, Missouri, United States
Saint Vincent Frontier Cancer Center
Billings, Montana, United States
Memorial Sloan Kettering Basking Ridge
Basking Ridge, New Jersey, United States
Memorial Sloan Kettering Monmouth
Middletown, New Jersey, United States
Memorial Sloan Kettering Bergen
Montvale, New Jersey, United States
Memorial Sloan Kettering Commack
Commack, New York, United States
Glens Falls Hospital
Glens Falls, New York, United States
Memorial Sloan Kettering Westchester
Harrison, New York, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
University of Rochester
Rochester, New York, United States
Memorial Sloan Kettering Nassau
Uniondale, New York, United States
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, United States
Southeastern Medical Oncology Center-Clinton
Clinton, North Carolina, United States
Levine Cancer Institute-Gaston
Gastonia, North Carolina, United States
Southeastern Medical Oncology Center-Goldsboro
Goldsboro, North Carolina, United States
Southeastern Medical Oncology Center-Jacksonville
Jacksonville, North Carolina, United States
Strecker Cancer Center-Belpre
Belpre, Ohio, United States
Adena Regional Medical Center
Chillicothe, Ohio, United States
Mount Carmel East Hospital
Columbus, Ohio, United States
Columbus Oncology and Hematology Associates Inc
Columbus, Ohio, United States
Riverside Methodist Hospital
Columbus, Ohio, United States
Grant Medical Center
Columbus, Ohio, United States
The Mark H Zangmeister Center
Columbus, Ohio, United States
Mount Carmel Health Center West
Columbus, Ohio, United States
Doctors Hospital
Columbus, Ohio, United States
Delaware Health Center-Grady Cancer Center
Delaware, Ohio, United States
Grady Memorial Hospital
Delaware, Ohio, United States
Dublin Methodist Hospital
Dublin, Ohio, United States
Central Ohio Breast and Endocrine Surgery
Gahanna, Ohio, United States
Mount Carmel Grove City Hospital
Grove City, Ohio, United States
Fairfield Medical Center
Lancaster, Ohio, United States
Saint Rita's Medical Center
Lima, Ohio, United States
OhioHealth Mansfield Hospital
Mansfield, Ohio, United States
Marietta Memorial Hospital
Marietta, Ohio, United States
OhioHealth Marion General Hospital
Marion, Ohio, United States
Knox Community Hospital
Mount Vernon, Ohio, United States
Licking Memorial Hospital
Newark, Ohio, United States
Newark Radiation Oncology
Newark, Ohio, United States
Mercy Health - Perrysburg Hospital
Perrysburg, Ohio, United States
Southern Ohio Medical Center
Portsmouth, Ohio, United States
Mercy Health - Saint Vincent Hospital
Toledo, Ohio, United States
Mercy Health - Saint Anne Hospital
Toledo, Ohio, United States
Saint Ann's Hospital
Westerville, Ohio, United States
Genesis Healthcare System Cancer Care Center
Zanesville, Ohio, United States
Providence Cancer Institute Clackamas Clinic
Clackamas, Oregon, United States
Providence Newberg Medical Center
Newberg, Oregon, United States
Providence Willamette Falls Medical Center
Oregon City, Oregon, United States
Providence Portland Medical Center
Portland, Oregon, United States
Providence Saint Vincent Medical Center
Portland, Oregon, United States
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, United States
Swedish Cancer Institute-Edmonds
Edmonds, Washington, United States
Swedish Cancer Institute-Issaquah
Issaquah, Washington, United States
Swedish Medical Center-First Hill
Seattle, Washington, United States
Marshfield Medical Center-EC Cancer Center
Eau Claire, Wisconsin, United States
Gundersen Lutheran Medical Center
La Crosse, Wisconsin, United States
Marshfield Medical Center-Marshfield
Marshfield, Wisconsin, United States
Marshfield Medical Center - Minocqua
Minocqua, Wisconsin, United States
Marshfield Medical Center-Rice Lake
Rice Lake, Wisconsin, United States
Marshfield Medical Center-River Region at Stevens Point
Stevens Point, Wisconsin, United States
Marshfield Medical Center - Weston
Weston, Wisconsin, United States
Countries
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Other Identifiers
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NCI-2021-02851
Identifier Type: REGISTRY
Identifier Source: secondary_id
S2005
Identifier Type: OTHER
Identifier Source: secondary_id
S2005
Identifier Type: OTHER
Identifier Source: secondary_id
NCI-2021-02851
Identifier Type: -
Identifier Source: org_study_id