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RECRUITING

NCT04840602

PHASE2

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

Sponsor: National Cancer Institute (NCI)

View on ClinicalTrials.gov

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.

Official title: A Phase II Randomized Study Comparing BTK Inhibitors (Ibrutinib Plus Rituximab or Zanubrutinib Alone) vs. BCL-2 Inhibitor (Venetoclax) and Rituximab in Previously Untreated Waldenström's Macroglobulinemia (WM) / Lymphoplasmacytic Lymphoma (LPL)

Key Details

Gender

All

Age Range

18 Years - Any

Study Type

INTERVENTIONAL

Enrollment

Start Date

2022-01-05

Completion Date

2028-03-31

Last Updated

2026-04-09

Healthy Volunteers

Conditions

Lymphoplasmacytic Lymphoma Waldenstrom Macroglobulinemia

Interventions

PROCEDURE

Biospecimen Collection

Undergo blood sample collection

PROCEDURE

Bone Marrow Aspiration

Undergo bone marrow biopsy and aspiration

PROCEDURE

Bone Marrow Biopsy

Undergo bone marrow biopsy and aspiration

PROCEDURE

Computed Tomography

Undergo CT or PET/CT

DRUG

Ibrutinib

Given PO

PROCEDURE

Positron Emission Tomography

Undergo PET/CT

BIOLOGICAL

Rituximab

Given IV

DRUG

Venetoclax

Given PO

DRUG

Zanubrutinib

Given PO

Inclusion Criteria: * Participants must have had a confirmed diagnosis of Waldenstrom's macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL). Participants must have measurable disease as determined by IgM protein quantification. * 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 ≥ 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 \>= 7.0 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/Z 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 \>= 7.0 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

Locations (125)

Banner University Medical Center - Tucson

Tucson, Arizona, United States

University of Arizona Cancer Center-North Campus

Tucson, Arizona, United States

UM Sylvester Comprehensive Cancer Center at Coral Gables

Coral Gables, Florida, United States

UM Sylvester Comprehensive Cancer Center at Coral Springs

Coral Springs, Florida, United States

UM Sylvester Comprehensive Cancer Center at Deerfield Beach

Deerfield Beach, Florida, United States

UM Sylvester Comprehensive Cancer Center at Doral

Doral, Florida, United States

UM Sylvester Comprehensive Cancer Center at Hollywood

Hollywood, Florida, United States

Mayo Clinic in Florida

Jacksonville, Florida, United States

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, United States

UM Sylvester Comprehensive Cancer Center at Kendall

Miami, Florida, United States

University of Miami Sylvester Comprehensive Cancer Center at Sole Mia

North Miami, Florida, United States

UM Sylvester Comprehensive Cancer Center at Plantation

Plantation, 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 Macomb Hospital-Clinton Township

Clinton Township, 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

Henry Ford Medical Center-Columbus

Novi, 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

Henry Ford West Bloomfield Hospital

West Bloomfield, 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

Clinical Research Directory

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

Summary

Key Details

Conditions

Interventions

Eligibility Criteria

Locations (125)