AzTrials
AzTrials

Lymphoplasmacytic LymphomaPhase 2NCT04840602

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

A Phase 2 study testing Biospecimen Collection, Bone Marrow Aspiration and Bone Marrow Biopsy in people with Lymphoplasmacytic Lymphoma and Waldenstrom Macroglobulinemia, run by National Cancer Institute (NCI) at 150 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Biospecimen Collection, Bone Marrow Aspiration and Bone Marrow Biopsy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
92 participants
Where
150 sitesUnited States
Study dates
5 Jan 2022to 31 Mar 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 52Show fewer
  • 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

Who cannot join

None listed.

Trial locations and contacts

150 sites in 1 country. Contact the study team or a site near you to ask about taking part.

150 sites in 1 country

United States150 sites, 106 recruiting

  • Mary Greeley Medical Center

    Ames, Iowa, 50010

    Site Public Contact, 515-956-4132

    Joseph J. Merchant

    Recruiting

  • McFarland Clinic - Ames

    Ames, Iowa, 50010

    Site Public Contact, 515-239-4734, ksoder@mcfarlandclinic.com

    Joseph J. Merchant

    Recruiting

  • Trinity Health Saint Joseph Mercy Hospital Ann Arbor

    Ann Arbor, Michigan, 48106

    Site Public Contact, 734-712-7251, MCRCwebsitecontactform@stjoeshealth.org

    Tareq Al baghdadi

    Recruiting

  • ThedaCare Regional Cancer Center

    Appleton, Wisconsin, 54911

    Site Public Contact, 920-364-3604, ResearchDept@thedacare.org

    Yazhini Vallatharasu

    Recruiting

  • Saint Alphonsus Cancer Care Center-Baker City

    Baker City, Oregon, 97814

    Site Public Contact, 406-969-6060, mccinfo@mtcancer.org

    Tareq Al baghdadi

    Recruiting

  • Memorial Sloan Kettering Basking Ridge

    Basking Ridge, New Jersey, 07920

    Site Public Contact, 212-639-7592

    Maria L. Palomba

    Recruiting

  • Strecker Cancer Center-Belpre

    Belpre, Ohio, 45714

    Suspended

  • Saint Vincent Frontier Cancer Center

    Billings, Montana, 59102

    Site Public Contact, 800-648-6274

    Patrick W. Cobb

    Recruiting

  • Saint Alphonsus Cancer Care Center-Boise

    Boise, Idaho, 83706

    Site Public Contact, 734-712-3671, stephanie.couch@stjoeshealth.org

    Tareq Al baghdadi

    Recruiting

  • McFarland Clinic - Boone

    Boone, Iowa, 50036

    Suspended

  • Trinity Health IHA Medical Group Hematology Oncology - Brighton

    Brighton, Michigan, 48114

    Site Public Contact, 734-712-7251, MCRCwebsitecontactform@stjoeshealth.org

    Tareq Al baghdadi

    Recruiting

  • Trinity Health Medical Center - Brighton

    Brighton, Michigan, 48114

    Site Public Contact, 734-712-7251, MCRCwebsitecontactform@stjoeshealth.org

    Tareq Al baghdadi

    Recruiting

  • Henry Ford Cancer Institute-Downriver

    Brownstown, Michigan, 48183

    Site Public Contact, 313-916-3721, CTOResearch@hfhs.org

    Vijayalakshmi Donthireddy

    Recruiting

  • Lahey Clinic

    Burlington, Massachusetts, 01805

    Site Public Contact, 781-744-3421, lhmc-cancer-clinical-trials@lahey.org

    Julio Hajdenberg

    Recruiting

  • Saint Alphonsus Cancer Care Center-Caldwell

    Caldwell, Idaho, 83605

    Site Public Contact, 734-712-3671, stephanie.couch@stjoeshealth.org

    Tareq Al baghdadi

    Recruiting

  • Trinity Health IHA Medical Group Hematology Oncology - Canton

    Canton, Michigan, 48188

    Site Public Contact, 734-712-7251, MCRCwebsitecontactform@stjoeshealth.org

    Tareq Al baghdadi

    Recruiting

  • Trinity Health Medical Center - Canton

    Canton, Michigan, 48188

    Site Public Contact, 734-712-7251, MCRCwebsitecontactform@stjoeshealth.org

    Tareq Al baghdadi

    Recruiting

  • Saint Francis Medical Center

    Cape Girardeau, Missouri, 63703

    Site Public Contact, 573-334-2230, sfmc@sfmc.net

    Bryan A. Faller

    Recruiting

  • Centralia Oncology Clinic

    Centralia, Illinois, 62801

    Site Public Contact, 217-876-4762, morganthaler.jodi@mhsil.com

    Bryan A. Faller

    Recruiting

  • Carolinas Medical Center/Levine Cancer Institute

    Charlotte, North Carolina, 28203

    Site Public Contact, 800-804-9376

    Manisha Bhutani

    Recruiting

  • Chelsea Hospital

    Chelsea, Michigan, 48118

    Site Public Contact, 734-712-7251, MCRCwebsitecontactform@stjoeshealth.org

    Tareq Al baghdadi

    Recruiting

  • Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital

    Chelsea, Michigan, 48118

    Site Public Contact, 734-712-7251, MCRCwebsitecontactform@stjoeshealth.org

    Tareq Al baghdadi

    Recruiting

  • Adena Regional Medical Center

    Chillicothe, Ohio, 45601

    Suspended

  • Siteman Cancer Center at Saint Peters Hospital

    City of Saint Peters, Missouri, 63376

    Active, not recruiting

  • Providence Cancer Institute Clackamas Clinic

    Clackamas, Oregon, 97015

    Suspended

  • Hematology Oncology Consultants-Clarkston

    Clarkston, Michigan, 48346

    Site Public Contact, 734-712-7251, MCRCwebsitecontactform@stjoeshealth.org

    Tareq Al baghdadi

    Recruiting

  • Newland Medical Associates-Clarkston

    Clarkston, Michigan, 48346

    Suspended

  • Southeastern Medical Oncology Center-Clinton

    Clinton, North Carolina, 28328

    Site Public Contact, 919-587-9084, jfields@cancersmoc.com

    Samer S. Kasbari

    Recruiting

  • Henry Ford Macomb Hospital-Clinton Township

    Clinton Township, Michigan, 48038

    Site Public Contact, 313-916-3721, CTOResearch@hfhs.org

    Vijayalakshmi Donthireddy

    Recruiting

  • Mount Carmel East Hospital

    Columbus, Ohio, 43213

    Suspended

  • Columbus Oncology and Hematology Associates Inc

    Columbus, Ohio, 43214

    Suspended

  • Riverside Methodist Hospital

    Columbus, Ohio, 43214

    Suspended

  • Grant Medical Center

    Columbus, Ohio, 43215

    Suspended

  • The Mark H Zangmeister Center

    Columbus, Ohio, 43219

    Suspended

  • Mount Carmel Health Center West

    Columbus, Ohio, 43222

    Suspended

  • Doctors Hospital

    Columbus, Ohio, 43228

    Suspended

  • Memorial Sloan Kettering Commack

    Commack, New York, 11725

    Site Public Contact, 212-639-7592

    Maria L. Palomba

    Recruiting

  • Mercy Hospital

    Coon Rapids, Minnesota, 55433

    Site Public Contact, 952-993-1517, mmcorc@healthpartners.com

    David M. King

    Recruiting

  • UM Sylvester Comprehensive Cancer Center at Coral Gables

    Coral Gables, Florida, 33146

    Site Public Contact, 305-243-2647

    Georgios Pongas

    Recruiting

  • UM Sylvester Comprehensive Cancer Center at Coral Springs

    Coral Springs, Florida, 33065

    Site Public Contact, 305-243-2647

    Georgios Pongas

    Recruiting

  • Siteman Cancer Center at West County Hospital

    Creve Coeur, Missouri, 63141

    Active, not recruiting

  • Carle at The Riverfront

    Danville, Illinois, 61832

    Site Public Contact, 800-446-5532, Research@Carle.com

    Priyank P. Patel

    Recruiting

  • Henry Ford Medical Center-Fairlane

    Dearborn, Michigan, 48126

    Site Public Contact, 313-916-3721, CTOResearch@hfhs.org

    Vijayalakshmi Donthireddy

    Recruiting

  • Cancer Care Specialists of Illinois - Decatur

    Decatur, Illinois, 62526

    Site Public Contact, 217-876-4762, morganthaler.jodi@mhsil.com

    Bryan A. Faller

    Recruiting

  • UM Sylvester Comprehensive Cancer Center at Deerfield Beach

    Deerfield Beach, Florida, 33442

    Site Public Contact, 305-243-2647

    Georgios Pongas

    Recruiting

  • Delaware Health Center-Grady Cancer Center

    Delaware, Ohio, 43015

    Suspended

  • Grady Memorial Hospital

    Delaware, Ohio, 43015

    Suspended

  • Wayne State University/Karmanos Cancer Institute

    Detroit, Michigan, 48201

    Site Public Contact, 800-527-6266, ctoadmin@karmanos.org

    Andrew Kin

    Recruiting

  • Henry Ford Hospital

    Detroit, Michigan, 48202

    Site Public Contact, 313-916-3721, CTOResearch@hfhs.org

    Vijayalakshmi Donthireddy

    Recruiting

  • UM Sylvester Comprehensive Cancer Center at Doral

    Doral, Florida, 33166

    Site Public Contact, kginnity@med.miami.edu

    Georgios Pongas

    Recruiting

  • Dublin Methodist Hospital

    Dublin, Ohio, 43016

    Suspended

  • Marshfield Medical Center-EC Cancer Center

    Eau Claire, Wisconsin, 54701

    Active, not recruiting

  • Minnesota Oncology - Edina

    Edina, Minnesota, 55435

    Site Public Contact, 952-993-1517, mmcorc@healthpartners.com

    David M. King

    Recruiting

  • Swedish Cancer Institute-Edmonds

    Edmonds, Washington, 98026

    Site Public Contact, 206-215-2343, PCRC-NCORP@Swedish.org

    Charles W. Drescher

    Recruiting

  • Carle Physician Group-Effingham

    Effingham, Illinois, 62401

    Site Public Contact, 800-446-5532, Research@carle.com

    Priyank P. Patel

    Recruiting

  • Crossroads Cancer Center

    Effingham, Illinois, 62401

    Site Public Contact, 217-876-4762, morganthaler.jodi@mhsil.com

    Bryan A. Faller

    Recruiting

  • Weisberg Cancer Treatment Center

    Farmington Hills, Michigan, 48334

    Site Public Contact, 313-576-9790, ctoadmin@karmanos.org

    Andrew Kin

    Recruiting

  • Cancer Hematology Centers - Flint

    Flint, Michigan, 48503

    Site Public Contact, 810-762-8038, wstrong@ghci.org

    Tareq Al baghdadi

    Recruiting

  • Genesee Hematology Oncology PC

    Flint, Michigan, 48503

    Suspended

  • Genesys Hurley Cancer Institute

    Flint, Michigan, 48503

    Site Public Contact, 810-762-8038, wstrong@ghci.org

    Tareq Al baghdadi

    Recruiting

  • Hurley Medical Center

    Flint, Michigan, 48503

    Site Public Contact, 810-762-8038, wstrong@ghci.org

    Tareq Al baghdadi

    Recruiting

  • McFarland Clinic - Trinity Cancer Center

    Fort Dodge, Iowa, 50501

    Site Public Contact, 515-956-4132

    Joseph J. Merchant

    Recruiting

  • Central Ohio Breast and Endocrine Surgery

    Gahanna, Ohio, 43230

    Suspended

  • Levine Cancer Institute-Gaston

    Gastonia, North Carolina, 28054

    Site Public Contact, 800-804-9376

    Manisha Bhutani

    Recruiting

  • Glens Falls Hospital

    Glens Falls, New York, 12801

    Active, not recruiting

  • Southeastern Medical Oncology Center-Goldsboro

    Goldsboro, North Carolina, 27534

    Site Public Contact, 919-587-9084, jfields@cancersmoc.com

    Samer S. Kasbari

    Recruiting

  • Mount Carmel Grove City Hospital

    Grove City, Ohio, 43123

    Suspended

  • Memorial Sloan Kettering Westchester

    Harrison, New York, 10604

    Site Public Contact, 212-639-7592

    Maria L. Palomba

    Recruiting

  • UM Sylvester Comprehensive Cancer Center at Hollywood

    Hollywood, Florida, 33021

    Site Public Contact, 305-243-2647

    Georgios Pongas

    Recruiting

  • City of Hope at Irvine Lennar

    Irvine, California, 92618

    Site Public Contact, 877-467-3411

    Benjamin M. Heyman

    Recruiting

  • Swedish Cancer Institute-Issaquah

    Issaquah, Washington, 98029

    Site Public Contact, 206-215-2343, PCRC-NCORP@Swedish.org

    Charles W. Drescher

    Recruiting

  • Allegiance Health

    Jackson, Michigan, 49201

    Site Public Contact, 313-916-3721, CTOResearch@hfhs.org

    Vijayalakshmi Donthireddy

    Recruiting

  • Mayo Clinic in Florida

    Jacksonville, Florida, 32224-9980

    Site Public Contact, 855-776-0015

    Sikander Ailawadhi

    Recruiting

  • Southeastern Medical Oncology Center-Jacksonville

    Jacksonville, North Carolina, 28546

    Site Public Contact, 910-587-9084, jfields@cancersmoc.com

    Samer S. Kasbari

    Recruiting

  • McFarland Clinic - Jefferson

    Jefferson, Iowa, 50129

    Suspended

  • Gundersen Lutheran Medical Center

    La Crosse, Wisconsin, 54601

    Site Public Contact, 608-775-2385, cancerctr@gundersenhealth.org

    David E. Marinier

    Recruiting

  • Fairfield Medical Center

    Lancaster, Ohio, 43130

    Suspended

  • University of Michigan Health - Sparrow Lansing

    Lansing, Michigan, 48912

    Site Public Contact, 517-364-3712, harsha.trivedi@umhsparrow.org

    Tareq Al baghdadi

    Recruiting

  • Saint Rita's Medical Center

    Lima, Ohio, 45801

    Suspended

  • Trinity Health Saint Mary Mercy Livonia Hospital

    Livonia, Michigan, 48154

    Site Public Contact, 734-712-7251, MCRCwebsitecontactform@stjoeshealth.org

    Tareq Al baghdadi

    Recruiting

  • OhioHealth Mansfield Hospital

    Mansfield, Ohio, 44903

    Suspended

  • Marietta Memorial Hospital

    Marietta, Ohio, 45750

    Suspended

  • OhioHealth Marion General Hospital

    Marion, Ohio, 43302

    Suspended

  • McFarland Clinic - Marshalltown

    Marshalltown, Iowa, 50158

    Site Public Contact, 515-956-4132

    Joseph J. Merchant

    Recruiting

  • Marshfield Medical Center-Marshfield

    Marshfield, Wisconsin, 54449

    Active, not recruiting

  • Carle Physician Group-Mattoon/Charleston

    Mattoon, Illinois, 61938

    Site Public Contact, 800-446-5532, Research@carle.com

    Priyank P. Patel

    Recruiting

  • Loyola University Medical Center

    Maywood, Illinois, 60153

    Site Public Contact, 708-226-4357

    Patrick A. Hagen

    Recruiting

  • Idaho Urologic Institute-Meridian

    Meridian, Idaho, 83642

    Site Public Contact, 734-712-3671, stephanie.couch@stjoeshealth.org

    Tareq Al baghdadi

    Recruiting

  • University of Miami Miller School of Medicine-Sylvester Cancer Center

    Miami, Florida, 33136

    Site Public Contact, 305-243-2647

    Georgios Pongas

    Recruiting

  • UM Sylvester Comprehensive Cancer Center at Kendall

    Miami, Florida, 33176

    Site Public Contact, 305-243-2647

    Georgios Pongas

    Recruiting

  • Memorial Sloan Kettering Monmouth

    Middletown, New Jersey, 07748

    Site Public Contact, 212-639-7592

    Maria L. Palomba

    Recruiting

  • Abbott-Northwestern Hospital

    Minneapolis, Minnesota, 55407

    Site Public Contact, 952-993-1517, mmcorc@healthpartners.com

    David M. King

    Recruiting

  • Hennepin County Medical Center

    Minneapolis, Minnesota, 55415

    Site Public Contact, 952-993-1517, mmcorc@healthpartners.com

    David M. King

    Recruiting

  • Marshfield Medical Center - Minocqua

    Minocqua, Wisconsin, 54548

    Active, not recruiting

  • Atrium Health Union/LCI-Union

    Monroe, North Carolina, 28112

    Site Public Contact, 980-442-2000

    Manisha Bhutani

    Recruiting

  • Memorial Sloan Kettering Bergen

    Montvale, New Jersey, 07645

    Site Public Contact, 212-639-7592

    Maria L. Palomba

    Recruiting

  • Knox Community Hospital

    Mount Vernon, Ohio, 43050

    Suspended

  • Saint Alphonsus Cancer Care Center-Nampa

    Nampa, Idaho, 83687

    Site Public Contact, 406-969-6060, mccinfo@mtcancer.org

    Tareq Al baghdadi

    Recruiting

  • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

    New York, New York, 10032

    Active, not recruiting

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

    Site Public Contact, 212-639-7592

    Maria L. Palomba

    Recruiting

  • Licking Memorial Hospital

    Newark, Ohio, 43055

    Site Public Contact, 614-488-2745, Jeffh@columbusccop.org

    Aruna C. Gowda

    Recruiting

  • Newark Radiation Oncology

    Newark, Ohio, 43055

    Suspended

  • Providence Newberg Medical Center

    Newberg, Oregon, 97132

    Site Public Contact, 503-215-2614, CanRsrchStudies@providence.org

    Charles W. Drescher

    Recruiting

  • University of Miami Sylvester Comprehensive Cancer Center at Sole Mia

    North Miami, Florida, 33181

    Site Public Contact, kginnity@med.miami.edu

    Georgios Pongas

    Recruiting

  • Henry Ford Medical Center-Columbus

    Novi, Michigan, 48377

    Site Public Contact, 313-916-3721, CTOResearch@hfhs.org

    Vijayalakshmi Donthireddy

    Recruiting

  • Cancer Care Center of O'Fallon

    O'Fallon, Illinois, 62269

    Site Public Contact, 217-876-4762, morganthaler.jodi@mhsil.com

    Bryan A. Faller

    Recruiting

  • Saint Alphonsus Cancer Care Center-Ontario

    Ontario, Oregon, 97914

    Site Public Contact, 406-969-6060, mccinfo@mtcancer.org

    Tareq Al baghdadi

    Recruiting

  • Providence Willamette Falls Medical Center

    Oregon City, Oregon, 97045

    Site Public Contact, 503-215-2614, CanRsrchStudies@providence.org

    Charles W. Drescher

    Recruiting

  • Mercy Health - Perrysburg Hospital

    Perrysburg, Ohio, 43551

    Suspended

  • UM Sylvester Comprehensive Cancer Center at Plantation

    Plantation, Florida, 33324

    Site Public Contact, 305-243-2647

    Georgios Pongas

    Recruiting

  • Michigan Healthcare Professionals Pontiac

    Pontiac, Michigan, 48341

    Site Public Contact, 248-858-6215, Emily.Crofts@trinity-health.org

    Tareq Al baghdadi

    Recruiting

  • Trinity Health IHA Medical Group-Alice Gustafson Center

    Pontiac, Michigan, 48341

    Site Public Contact, 734-712-7251, MCRCwebsitecontactform@stjoeshealth.org

    Tareq Al baghdadi

    Recruiting

  • Trinity Health Saint Joseph Mercy Oakland Hospital

    Pontiac, Michigan, 48341

    Site Public Contact, 734-712-7251, MCRCwebsitecontactform@stjoeshealth.org

    Tareq Al baghdadi

    Recruiting

  • Providence Portland Medical Center

    Portland, Oregon, 97213

    Site Public Contact, 503-215-2614, CanRsrchStudies@providence.org

    Charles W. Drescher

    Recruiting

  • Providence Saint Vincent Medical Center

    Portland, Oregon, 97225

    Site Public Contact, 503-215-2614, CanRsrchStudies@providence.org

    Charles W. Drescher

    Recruiting

  • Southern Ohio Medical Center

    Portsmouth, Ohio, 45662

    Suspended

  • Marshfield Medical Center-Rice Lake

    Rice Lake, Wisconsin, 54868

    Active, not recruiting

  • VCU Massey Comprehensive Cancer Center

    Richmond, Virginia, 23298

    Site Public Contact, 804-628-6430, CTOclinops@vcu.edu

    Bharadhwaj Kolipakkam

    Recruiting

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

    Site Public Contact, 855-776-0015

    Sikander Ailawadhi

    Recruiting

  • University of Rochester

    Rochester, New York, 14642

    Site Public Contact, 585-275-5830

    Clive S. Zent

    Recruiting

  • MyMichigan Medical Center Saginaw

    Saginaw, Michigan, 48601

    Site Public Contact, 734-712-7251, MCRCwebsitecontactform@stjoeshealth.org

    Tareq Al baghdadi

    Recruiting

  • Oncology Hematology Associates of Saginaw Valley PC

    Saginaw, Michigan, 48604

    Suspended

  • Heartland Regional Medical Center

    Saint Joseph, Missouri, 64506

    Site Public Contact, 816-271-7937, Trisha.England2@mymlc.com

    Jay W. Carlson

    Recruiting

  • Park Nicollet Clinic - Saint Louis Park

    Saint Louis Park, Minnesota, 55416

    Site Public Contact, 952-993-1517, mmcorc@healthpartners.com

    David M. King

    Recruiting

  • Regions Hospital

    Saint Paul, Minnesota, 55101

    Site Public Contact, 952-993-1517, mmcorc@healthpartners.com

    David M. King

    Recruiting

  • United Hospital

    Saint Paul, Minnesota, 55102

    Site Public Contact, 952-993-1517, mmcorc@healthpartners.com

    David M. King

    Recruiting

  • Swedish Medical Center-First Hill

    Seattle, Washington, 98122

    Site Public Contact, 206-215-2343, PCRC-NCORP@Swedish.org

    Charles W. Drescher

    Recruiting

  • Southern Illinois University School of Medicine

    Springfield, Illinois, 62702

    Site Public Contact, 217-545-7929

    Bryan A. Faller

    Recruiting

  • Springfield Clinic

    Springfield, Illinois, 62702

    Site Public Contact, 800-444-7541

    Bryan A. Faller

    Recruiting

  • Springfield Memorial Hospital

    Springfield, Illinois, 62781

    Site Public Contact, 217-528-7541, pallante.beth@mhsil.com

    Bryan A. Faller

    Recruiting

  • Washington University School of Medicine

    St Louis, Missouri, 63110

    Active, not recruiting

  • Mercy Hospital South

    St Louis, Missouri, 63128

    Site Public Contact, 314-525-6042, Danielle.Werle@mercy.net

    Jay W. Carlson

    Recruiting

  • Siteman Cancer Center-South County

    St Louis, Missouri, 63129

    Active, not recruiting

  • Siteman Cancer Center at Christian Hospital

    St Louis, Missouri, 63136

    Active, not recruiting

  • Marshfield Medical Center-River Region at Stevens Point

    Stevens Point, Wisconsin, 54482

    Site Public Contact, 800-782-8581, oncology.clinical.trials@marshfieldresearch.org

    Adedayo A. Onitilo

    Recruiting

  • MyMichigan Medical Center Tawas

    Tawas City, Michigan, 48764

    Site Public Contact, 734-712-7251, MCRCwebsitecontactform@stjoeshealth.org

    Tareq Al baghdadi

    Recruiting

  • Mercy Health - Saint Vincent Hospital

    Toledo, Ohio, 43608

    Suspended

  • Mercy Health - Saint Anne Hospital

    Toledo, Ohio, 43623

    Suspended

  • Banner University Medical Center - Tucson

    Tucson, Arizona, 85719

    Site Public Contact, UACC-IIT@uacc.arizona.edu

    Muhammad Husnain

    Recruiting

  • University of Arizona Cancer Center-North Campus

    Tucson, Arizona, 85719

    Site Public Contact, UACC-IIT@uacc.arizona.edu

    Muhammad Husnain

    Recruiting

  • Memorial Sloan Kettering Nassau

    Uniondale, New York, 11553

    Site Public Contact, 212-639-7592

    Maria L. Palomba

    Recruiting

  • Carle Cancer Center

    Urbana, Illinois, 61801

    Site Public Contact, 800-446-5532, Research@carle.com

    Priyank P. Patel

    Recruiting

  • Wilmot Cancer Institute at Webster

    Webster, New York, 14580

    Site Public Contact, WCICTOresearch@urmc.rochester.edu

    Clive S. Zent

    Recruiting

  • Henry Ford West Bloomfield Hospital

    West Bloomfield, Michigan, 48322

    Site Public Contact, 313-916-3721, CTOResearch@hfhs.org

    Vijayalakshmi Donthireddy

    Recruiting

  • Saint Ann's Hospital

    Westerville, Ohio, 43081

    Suspended

  • Marshfield Medical Center - Weston

    Weston, Wisconsin, 54476

    Site Public Contact, 800-782-8581, oncology.clinical.trials@marshfieldresearch.org

    Adedayo A. Onitilo

    Recruiting

  • Henry Ford Wyandotte Hospital

    Wyandotte, Michigan, 48192

    Site Public Contact, nhay@hfhs.org

    Vijayalakshmi Donthireddy

    Recruiting

  • Huron Gastroenterology PC

    Ypsilanti, Michigan, 48106

    Site Public Contact, 734-712-7251, MCRCwebsitecontactform@stjoeshealth.org

    Tareq Al baghdadi

    Recruiting

  • Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus

    Ypsilanti, Michigan, 48197

    Site Public Contact, 734-712-7251, MCRCwebsitecontactform@stjoeshealth.org

    Tareq Al baghdadi

    Recruiting

  • Genesis Healthcare System Cancer Care Center

    Zanesville, Ohio, 43701

    Suspended

Other trials in United States

About this study

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)

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. 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:

  1. 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.

  1. 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:

  1. 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.

Being tested
Biospecimen Collection, Bone Marrow Aspiration, Bone Marrow Biopsy, Computed Tomography, Ibrutinib
Medical subject headings
Lymphoma, B-Cell, Marginal Zone, Waldenstrom Macroglobulinemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo blood sample collection

  • Bone Marrow AspirationProcedure or surgery

    Undergo bone marrow biopsy and aspiration

  • Bone Marrow BiopsyProcedure or surgery

    Also called Biopsy of Bone Marrow, Biopsy, Bone Marrow

    Undergo bone marrow biopsy and aspiration

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT or PET/CT

  • IbrutinibDrug

    Also called BTK Inhibitor PCI-32765, CRA 032765, CRA-032765, CRA032765

    Given PO

  • Positron Emission TomographyProcedure or surgery

    Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)

    Undergo PET/CT

  • RituximabBiological

    Also called ABP 798, ABP-798, ABP798, BI 695500

    Given IV

  • VenetoclaxDrug

    Also called ABT 199, ABT-0199, ABT-199, ABT199

    Given PO

  • ZanubrutinibDrug

    Also called BGB 3111, BGB-3111, BGB3111, Brukinsa

    Given PO

Study groups in NCT04840602
Study groupRoleWhat they receive
Arm I (ibrutinib + rituximab or zanubrutinib)Active comparatorPatients 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, or zanubrutinib PO QD or 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 CT or PET/CT and bone marrow biopsy and aspiration as well as blood sample collection throughout the trial.
Receives: Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Drug: Ibrutinib; Procedure: Positron Emission Tomography; Biological: Rituximab; Drug: Zanubrutinib
Arm II (venetoclax, rituximab)ExperimentalPatients 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.
Receives: Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Procedure: Positron Emission Tomography; Biological: Rituximab; Drug: Venetoclax

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Very good partial response or better (VGPR or better) rate

    A Cochran-Mantel-Haenszel test will be performed to compare the VGPR in the ibrutinib plus rituximab or zanubrutinib alone arm and the venetoclax plus rituximab arm accounting for the stratification factor of prior rituximab, and VGPR or better rate will be reported in each study arm with a binomial confidence interval.

    Measured: Up to 5 years

Secondary outcomes (6)

  1. Progression-free survival

    Will be analyzed using the Kaplan-Meier method, and a stratified log-rank test will be performed to compare survival outcomes in the ibrutinib plus rituximab or zanubrutinib alone and venetoclax plus rituximab arms while controlling for the effects from the stratification factor of prior rituximab treatment.

    Measured: From the date of registration to the date of first documentation of progressive disease or symptomatic deterioration, or death due to any cause, assessed up to 5 years

  2. Overall survival

    Will be analyzed using the Kaplan-Meier method, and a stratified log-rank test will be performed to compare survival outcomes in the ibrutinib plus rituximab or zanubrutinib alone and venetoclax plus rituximab arms while controlling for the effects from the stratification factor of prior rituximab treatment.

    Measured: From the date of registration to the date of death due to any cause, assessed up to 5 years

  3. Rate of complete response

    Will be analyzed using the cumulative incidence competing risks method.

    Measured: From the date of registration to the date of complete response, assessed up to 5 years

  4. Overall response rate

    Defined as the percentage of participants achieving a best response of complete response, very good partial response, or partial response while on study. Will be reported with a binomial confidence interval.

    Measured: Up to 5 years

  5. Time to VGPR or better

    Defined as the percentage of participants achieving a best response of very good partial response or better while on study. Will be reported with a binomial confidence interval.

    Measured: Up to 5 years

  6. Incidence of adverse events

    As assessed by Common Terminology Criteria for Adverse Events Version 5.0.

    Measured: Up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Apr 2021
  2. Study start5 Jan 2022
  3. Primary completion31 Mar 2028 (estimated)
  4. Study completion31 Mar 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
None (open label)
Enrolment
92 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04840602
Sponsor's protocol ID
NCI-2021-02851
Other IDs
NCI-2021-02851, S2005, S2005, U10CA180888
Status last verified
Sep 2026
First submitted
9 Apr 2021
Last updated
30 Oct 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Biospecimen Collection, Bone Marrow Aspiration and Bone Marrow Biopsy in people with Lymphoplasmacytic Lymphoma and Waldenstrom Macroglobulinemia, run by National Cancer Institute (NCI) at 150 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 52 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 30 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 150 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Very good partial response or better (VGPR or better) rate (time frame: Up to 5 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04840602.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Oct 2026.

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