Testing the Combination of Venetoclax and Rituximab, in Comparison to the Usual Treatment (Ibrutinib and Rituximab) for Waldenstrom's Macroglobulinemia/Lymphoplasmacytic Lymphoma

January 9, 2025 updated by: National Cancer Institute (NCI)

A Phase II Randomized Study Comparing Ibrutinib and Rituximab vs. 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 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. Giving venetoclax and rituximab may work better in treating patients with previously untreated Waldenstrom's macroglobulinemia than ibrutinib and rituximab alone.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVE:

I. To compare the rate of very good partial response or better (VGPR or better) in previously untreated participants with Waldenström's macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) who are treated upfront with ibrutinib 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 1 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 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 during screening and on 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 1 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 during screening and on 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.

Study Type

Interventional

Enrollment (Estimated)

92

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Jacksonville, Florida, United States, 32224-9980
        • Recruiting
        • Mayo Clinic in Florida
        • Principal Investigator:
          • Sikander Ailawadhi
        • Contact:
          • Site Public Contact
          • Phone Number: 855-776-0015
    • Illinois
      • Centralia, Illinois, United States, 62801
        • Recruiting
        • Centralia Oncology Clinic
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
      • Danville, Illinois, United States, 61832
        • Recruiting
        • Carle at The Riverfront
        • Contact:
        • Principal Investigator:
          • Priyank P. Patel
      • Decatur, Illinois, United States, 62526
        • Recruiting
        • Cancer Care Specialists of Illinois - Decatur
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
      • Effingham, Illinois, United States, 62401
        • Recruiting
        • Carle Physician Group-Effingham
        • Contact:
        • Principal Investigator:
          • Priyank P. Patel
      • Effingham, Illinois, United States, 62401
        • Recruiting
        • Crossroads Cancer Center
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
      • Mattoon, Illinois, United States, 61938
        • Recruiting
        • Carle Physician Group-Mattoon/Charleston
        • Contact:
        • Principal Investigator:
          • Priyank P. Patel
      • O'Fallon, Illinois, United States, 62269
        • Recruiting
        • Cancer Care Center of O'Fallon
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
      • Springfield, Illinois, United States, 62702
        • Recruiting
        • Southern Illinois University School of Medicine
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
          • Site Public Contact
          • Phone Number: 217-545-7929
      • Springfield, Illinois, United States, 62702
        • Recruiting
        • Springfield Clinic
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
          • Site Public Contact
          • Phone Number: 800-444-7541
      • Springfield, Illinois, United States, 62781
        • Recruiting
        • Springfield Memorial Hospital
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
      • Urbana, Illinois, United States, 61801
        • Recruiting
        • Carle Cancer Center
        • Contact:
        • Principal Investigator:
          • Priyank P. Patel
    • Iowa
      • Ames, Iowa, United States, 50010
        • Recruiting
        • Mary Greeley Medical Center
        • Principal Investigator:
          • Joseph J. Merchant
        • Contact:
          • Site Public Contact
          • Phone Number: 515-956-4132
      • Ames, Iowa, United States, 50010
        • Recruiting
        • McFarland Clinic - Ames
        • Principal Investigator:
          • Joseph J. Merchant
        • Contact:
      • Boone, Iowa, United States, 50036
        • Recruiting
        • McFarland Clinic - Boone
        • Principal Investigator:
          • Joseph J. Merchant
        • Contact:
          • Site Public Contact
          • Phone Number: 515-956-4132
      • Fort Dodge, Iowa, United States, 50501
        • Recruiting
        • McFarland Clinic - Trinity Cancer Center
        • Principal Investigator:
          • Joseph J. Merchant
        • Contact:
          • Site Public Contact
          • Phone Number: 515-956-4132
      • Jefferson, Iowa, United States, 50129
        • Recruiting
        • McFarland Clinic - Jefferson
        • Principal Investigator:
          • Joseph J. Merchant
        • Contact:
          • Site Public Contact
          • Phone Number: 515-956-4132
      • Marshalltown, Iowa, United States, 50158
        • Recruiting
        • McFarland Clinic - Marshalltown
        • Principal Investigator:
          • Joseph J. Merchant
        • Contact:
          • Site Public Contact
          • Phone Number: 515-956-4132
    • Michigan
      • Ann Arbor, Michigan, United States, 48106
        • Recruiting
        • Trinity Health Saint Joseph Mercy Hospital Ann Arbor
        • Contact:
        • Principal Investigator:
          • Tareq Al baghdadi
      • Brighton, Michigan, United States, 48114
        • Recruiting
        • Trinity Health IHA Medical Group Hematology Oncology - Brighton
        • Contact:
        • Principal Investigator:
          • Tareq Al baghdadi
      • Brighton, Michigan, United States, 48114
        • Recruiting
        • Trinity Health Medical Center - Brighton
        • Contact:
        • Principal Investigator:
          • Tareq Al baghdadi
      • Canton, Michigan, United States, 48188
        • Recruiting
        • Trinity Health IHA Medical Group Hematology Oncology - Canton
        • Contact:
        • Principal Investigator:
          • Tareq Al baghdadi
      • Canton, Michigan, United States, 48188
        • Recruiting
        • Trinity Health Medical Center - Canton
        • Contact:
        • Principal Investigator:
          • Tareq Al baghdadi
      • Chelsea, Michigan, United States, 48118
        • Recruiting
        • Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
        • Contact:
        • Principal Investigator:
          • Tareq Al baghdadi
      • Chelsea, Michigan, United States, 48118
      • Clarkston, Michigan, United States, 48346
        • Recruiting
        • Hematology Oncology Consultants-Clarkston
        • Contact:
        • Principal Investigator:
          • Tareq Al baghdadi
      • Clarkston, Michigan, United States, 48346
      • Detroit, Michigan, United States, 48202
        • Active, not recruiting
        • Henry Ford Hospital
      • Flint, Michigan, United States, 48503
        • Recruiting
        • Genesee Hematology Oncology PC
        • Contact:
        • Principal Investigator:
          • Tareq Al baghdadi
      • Flint, Michigan, United States, 48503
        • Recruiting
        • Genesys Hurley Cancer Institute
        • Contact:
        • Principal Investigator:
          • Tareq Al baghdadi
      • Flint, Michigan, United States, 48503
        • Recruiting
        • Hurley Medical Center
        • Contact:
        • Principal Investigator:
          • Tareq Al baghdadi
      • Flint, Michigan, United States, 48503
        • Recruiting
        • Cancer Hematology Centers - Flint
        • Contact:
        • Principal Investigator:
          • Tareq Al baghdadi
      • Lansing, Michigan, United States, 48912
        • Recruiting
        • University of Michigan Health - Sparrow Lansing
        • Principal Investigator:
          • Tareq Al baghdadi
        • Contact:
      • Livonia, Michigan, United States, 48154
        • Recruiting
        • Trinity Health Saint Mary Mercy Livonia Hospital
        • Contact:
        • Principal Investigator:
          • Tareq Al baghdadi
      • Pontiac, Michigan, United States, 48341
      • Pontiac, Michigan, United States, 48341
        • Recruiting
        • Trinity Health Saint Joseph Mercy Oakland Hospital
        • Contact:
        • Principal Investigator:
          • Tareq Al baghdadi
      • Pontiac, Michigan, United States, 48341
        • Recruiting
        • Michigan Healthcare Professionals Pontiac
        • Principal Investigator:
          • Tareq Al baghdadi
        • Contact:
      • Saginaw, Michigan, United States, 48604
        • Recruiting
        • Oncology Hematology Associates of Saginaw Valley PC
        • Contact:
        • Principal Investigator:
          • Tareq Al baghdadi
      • Saginaw, Michigan, United States, 48601
      • Tawas City, Michigan, United States, 48764
      • Ypsilanti, Michigan, United States, 48106
      • Ypsilanti, Michigan, United States, 48197
        • Recruiting
        • Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
        • Contact:
        • Principal Investigator:
          • Tareq Al baghdadi
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Mayo Clinic in Rochester
        • Principal Investigator:
          • Sikander Ailawadhi
        • Contact:
          • Site Public Contact
          • Phone Number: 855-776-0015
    • Missouri
      • Cape Girardeau, Missouri, United States, 63703
        • Recruiting
        • Saint Francis Medical Center
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
          • Site Public Contact
          • Phone Number: 573-334-2230
          • Email: sfmc@sfmc.net
      • Creve Coeur, Missouri, United States, 63141
        • Active, not recruiting
        • Siteman Cancer Center at West County Hospital
      • Saint Louis, Missouri, United States, 63110
        • Active, not recruiting
        • Washington University School of Medicine
      • Saint Louis, Missouri, United States, 63129
        • Active, not recruiting
        • Siteman Cancer Center-South County
      • Saint Louis, Missouri, United States, 63136
        • Active, not recruiting
        • Siteman Cancer Center at Christian Hospital
      • Saint Peters, Missouri, United States, 63376
        • Active, not recruiting
        • Siteman Cancer Center at Saint Peters Hospital
    • New Jersey
      • Basking Ridge, New Jersey, United States, 07920
        • Recruiting
        • Memorial Sloan Kettering Basking Ridge
        • Contact:
          • Site Public Contact
          • Phone Number: 212-639-7592
        • Principal Investigator:
          • Maria L. Palomba
      • Middletown, New Jersey, United States, 07748
        • Recruiting
        • Memorial Sloan Kettering Monmouth
        • Contact:
          • Site Public Contact
          • Phone Number: 212-639-7592
        • Principal Investigator:
          • Maria L. Palomba
      • Montvale, New Jersey, United States, 07645
        • Recruiting
        • Memorial Sloan Kettering Bergen
        • Contact:
          • Site Public Contact
          • Phone Number: 212-639-7592
        • Principal Investigator:
          • Maria L. Palomba
    • New York
      • Commack, New York, United States, 11725
        • Recruiting
        • Memorial Sloan Kettering Commack
        • Contact:
          • Site Public Contact
          • Phone Number: 212-639-7592
        • Principal Investigator:
          • Maria L. Palomba
      • Glens Falls, New York, United States, 12801
        • Recruiting
        • Glens Falls Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 518-926-6700
        • Principal Investigator:
          • Christopher R. Mason
      • Harrison, New York, United States, 10604
        • Recruiting
        • Memorial Sloan Kettering Westchester
        • Contact:
          • Site Public Contact
          • Phone Number: 212-639-7592
        • Principal Investigator:
          • Maria L. Palomba
      • New York, New York, United States, 10065
        • Recruiting
        • Memorial Sloan Kettering Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 212-639-7592
        • Principal Investigator:
          • Maria L. Palomba
      • New York, New York, United States, 10032
        • Suspended
        • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
      • Rochester, New York, United States, 14642
        • Recruiting
        • University of Rochester
        • Contact:
          • Site Public Contact
          • Phone Number: 585-275-5830
        • Principal Investigator:
          • Paul M. Barr
      • Uniondale, New York, United States, 11553
        • Recruiting
        • Memorial Sloan Kettering Nassau
        • Contact:
          • Site Public Contact
          • Phone Number: 212-639-7592
        • Principal Investigator:
          • Maria L. Palomba
    • North Carolina
      • Clinton, North Carolina, United States, 28328
        • Recruiting
        • Southeastern Medical Oncology Center-Clinton
        • Contact:
        • Principal Investigator:
          • Samer S. Kasbari
      • Goldsboro, North Carolina, United States, 27534
        • Recruiting
        • Southeastern Medical Oncology Center-Goldsboro
        • Contact:
        • Principal Investigator:
          • Samer S. Kasbari
      • Jacksonville, North Carolina, United States, 28546
        • Recruiting
        • Southeastern Medical Oncology Center-Jacksonville
        • Principal Investigator:
          • Samer S. Kasbari
        • Contact:
    • Ohio
      • Belpre, Ohio, United States, 45714
        • Suspended
        • Strecker Cancer Center-Belpre
      • Chillicothe, Ohio, United States, 45601
        • Suspended
        • Adena Regional Medical Center
      • Columbus, Ohio, United States, 43213
        • Suspended
        • Mount Carmel East Hospital
      • Columbus, Ohio, United States, 43214
        • Suspended
        • Riverside Methodist Hospital
      • Columbus, Ohio, United States, 43222
        • Suspended
        • Mount Carmel Health Center West
      • Columbus, Ohio, United States, 43215
        • Suspended
        • Grant Medical Center
      • Columbus, Ohio, United States, 43219
        • Suspended
        • The Mark H Zangmeister Center
      • Columbus, Ohio, United States, 43228
        • Suspended
        • Doctors Hospital
      • Columbus, Ohio, United States, 43214
        • Suspended
        • Columbus Oncology and Hematology Associates Inc
      • Delaware, Ohio, United States, 43015
        • Suspended
        • Grady Memorial Hospital
      • Delaware, Ohio, United States, 43015
        • Suspended
        • Delaware Health Center-Grady Cancer Center
      • Dublin, Ohio, United States, 43016
        • Suspended
        • Dublin Methodist Hospital
      • Gahanna, Ohio, United States, 43230
        • Suspended
        • Central Ohio Breast and Endocrine Surgery
      • Grove City, Ohio, United States, 43123
        • Suspended
        • Mount Carmel Grove City Hospital
      • Lancaster, Ohio, United States, 43130
        • Suspended
        • Fairfield Medical Center
      • Lima, Ohio, United States, 45801
        • Suspended
        • Saint Rita's Medical Center
      • Mansfield, Ohio, United States, 44903
        • Suspended
        • OhioHealth Mansfield Hospital
      • Marietta, Ohio, United States, 45750
        • Suspended
        • Marietta Memorial Hospital
      • Marion, Ohio, United States, 43302
        • Suspended
        • OhioHealth Marion General Hospital
      • Mount Vernon, Ohio, United States, 43050
        • Suspended
        • Knox Community Hospital
      • Newark, Ohio, United States, 43055
        • Recruiting
        • Licking Memorial Hospital
        • Contact:
        • Principal Investigator:
          • William A. Wilson
      • Newark, Ohio, United States, 43055
        • Suspended
        • Newark Radiation Oncology
      • Perrysburg, Ohio, United States, 43551
        • Suspended
        • Mercy Health - Perrysburg Hospital
      • Portsmouth, Ohio, United States, 45662
        • Suspended
        • Southern Ohio Medical Center
      • Toledo, Ohio, United States, 43623
        • Suspended
        • Mercy Health - Saint Anne Hospital
      • Toledo, Ohio, United States, 43608
        • Suspended
        • Mercy Health - Saint Vincent Hospital
      • Westerville, Ohio, United States, 43081
        • Suspended
        • Saint Ann's Hospital
      • Zanesville, Ohio, United States, 43701
        • Suspended
        • Genesis Healthcare System Cancer Care Center
    • Oregon
      • Clackamas, Oregon, United States, 97015
        • Recruiting
        • Providence Cancer Institute Clackamas Clinic
        • Contact:
        • Principal Investigator:
          • Charles W. Drescher
      • Newberg, Oregon, United States, 97132
        • Recruiting
        • Providence Newberg Medical Center
        • Contact:
        • Principal Investigator:
          • Charles W. Drescher
      • Oregon City, Oregon, United States, 97045
        • Recruiting
        • Providence Willamette Falls Medical Center
        • Contact:
        • Principal Investigator:
          • Charles W. Drescher
      • Portland, Oregon, United States, 97213
        • Recruiting
        • Providence Portland Medical Center
        • Contact:
        • Principal Investigator:
          • Charles W. Drescher
      • Portland, Oregon, United States, 97225
        • Recruiting
        • Providence Saint Vincent Medical Center
        • Contact:
        • Principal Investigator:
          • Charles W. Drescher
    • Washington
      • Edmonds, Washington, United States, 98026
        • Recruiting
        • Swedish Cancer Institute-Edmonds
        • Contact:
        • Principal Investigator:
          • Charles W. Drescher
      • Issaquah, Washington, United States, 98029
        • Recruiting
        • Swedish Cancer Institute-Issaquah
        • Contact:
        • Principal Investigator:
          • Charles W. Drescher
      • Seattle, Washington, United States, 98122
        • Recruiting
        • Swedish Medical Center-First Hill
        • Contact:
        • Principal Investigator:
          • Charles W. Drescher
    • Wisconsin
      • Eau Claire, Wisconsin, United States, 54701
      • La Crosse, Wisconsin, United States, 54601
        • Recruiting
        • Gundersen Lutheran Medical Center
        • Contact:
        • Principal Investigator:
          • David E. Marinier
      • Marshfield, Wisconsin, United States, 54449
      • Minocqua, Wisconsin, United States, 54548
      • Stevens Point, Wisconsin, United States, 54482
      • Weston, Wisconsin, United States, 54476

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 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 (without transfusion or growth factor support within 14 days prior to registration)
  • Hemoglobin >= 8.0 g/dL (without transfusion or growth factor support within 14 days prior to registration)
  • Absolute neutrophil count (ANC) >= 1,000 cells/mm^3 (without transfusion or growth factor support within 14 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 fungal infections of nail beds) 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 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 transfusion or growth factor support within 14 days prior to registration)
  • CROSSOVER CRITERIA: Hemoglobin >= 8.0 g/dL (without transfusion or growth factor support within 14 days prior to registration)
  • CROSSOVER CRITERIA: Absolute neutrophil count (ANC) >= 1,000 cells/mm^3 (without transfusion or growth factor support within 14 days prior to registration)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 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 1 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 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 during screening and on the trial.
Procedure: Biospecimen Collection
Undergo blood sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Biological: Rituximab
Given IV
Other Names:
  • Rituxan
  • MabThera
  • ABP 798
  • BI 695500
  • C2B8 Monoclonal Antibody
  • Chimeric Anti-CD20 Antibody
  • CT-P10
  • IDEC-102
  • IDEC-C2B8
  • IDEC-C2B8 Monoclonal Antibody
  • Monoclonal Antibody IDEC-C2B8
  • PF-05280586
  • Riabni
  • Rituximab ABBS
  • Rituximab ARRX
  • Rituximab Biosimilar ABP 798
  • Rituximab Biosimilar BI 695500
  • Rituximab Biosimilar CT-P10
  • Rituximab Biosimilar GB241
  • Rituximab Biosimilar IBI301
  • Rituximab Biosimilar JHL1101
  • Rituximab Biosimilar PF-05280586
  • Rituximab Biosimilar RTXM83
  • Rituximab Biosimilar SAIT101
  • Rituximab Biosimilar SIBP-02
  • rituximab biosimilar TQB2303
  • Rituximab PVVR
  • Rituximab-arrx
  • Rituximab-pvvr
  • RTXM83
  • Ruxience
  • Truxima
  • Rixathon
  • Ikgdar
  • Mabtas
  • Rituximab-abbs
  • BI-695500
  • BI695500
  • Blitzima
  • IDEC 102
  • IDEC102
  • PF 05280586
  • PF05280586
  • Ritemvia
  • Rituximab-blit
  • Rituximab-rite
  • Rituximab-rixa
  • Rituximab-rixi
  • Riximyo
  • RTXM 83
  • RTXM-83
  • ABP-798
  • ABP798
  • CT P10
  • CTP10
  • GP 2013
  • GP-2013
  • GP2013
  • Rituximab Biosimilar GP2013
Drug: Ibrutinib
Given PO
Other Names:
  • PCI-32765
  • Imbruvica
  • BTK Inhibitor PCI-32765
  • CRA-032765
  • PCI32765
  • CRA 032765
  • CRA032765
  • PCI 32765
Procedure: Positron Emission Tomography
Undergo PET/CT
Other Names:
  • Medical Imaging, Positron Emission Tomography
  • PET
  • PET Scan
  • Positron Emission Tomography Scan
  • Positron-Emission Tomography
  • proton magnetic resonance spectroscopic imaging
  • PT
  • Positron emission tomography (procedure)
Procedure: Bone Marrow Biopsy
Undergo bone marrow biopsy and aspiration
Other Names:
  • Biopsy of Bone Marrow
  • Biopsy, Bone Marrow
Procedure: Computed Tomography
Undergo CT or PET/CT
Other Names:
  • CT
  • CAT
  • CAT Scan
  • Computed Axial Tomography
  • Computerized Axial Tomography
  • Computerized Tomography
  • CT Scan
  • tomography
  • Computerized axial tomography (procedure)
  • Computerized Tomography (CT) scan
Procedure: Bone Marrow Aspiration
Undergo bone marrow biopsy and aspiration
Experimental: 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 1 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 during screening and on the trial.
Procedure: Biospecimen Collection
Undergo blood sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Drug: Venetoclax
Given PO
Other Names:
  • Venclexta
  • ABT-0199
  • ABT-199
  • ABT199
  • GDC-0199
  • RG7601
  • Venclyxto
  • ABT 199
  • GDC 0199
  • GDC0199
Biological: Rituximab
Given IV
Other Names:
  • Rituxan
  • MabThera
  • ABP 798
  • BI 695500
  • C2B8 Monoclonal Antibody
  • Chimeric Anti-CD20 Antibody
  • CT-P10
  • IDEC-102
  • IDEC-C2B8
  • IDEC-C2B8 Monoclonal Antibody
  • Monoclonal Antibody IDEC-C2B8
  • PF-05280586
  • Riabni
  • Rituximab ABBS
  • Rituximab ARRX
  • Rituximab Biosimilar ABP 798
  • Rituximab Biosimilar BI 695500
  • Rituximab Biosimilar CT-P10
  • Rituximab Biosimilar GB241
  • Rituximab Biosimilar IBI301
  • Rituximab Biosimilar JHL1101
  • Rituximab Biosimilar PF-05280586
  • Rituximab Biosimilar RTXM83
  • Rituximab Biosimilar SAIT101
  • Rituximab Biosimilar SIBP-02
  • rituximab biosimilar TQB2303
  • Rituximab PVVR
  • Rituximab-arrx
  • Rituximab-pvvr
  • RTXM83
  • Ruxience
  • Truxima
  • Rixathon
  • Ikgdar
  • Mabtas
  • Rituximab-abbs
  • BI-695500
  • BI695500
  • Blitzima
  • IDEC 102
  • IDEC102
  • PF 05280586
  • PF05280586
  • Ritemvia
  • Rituximab-blit
  • Rituximab-rite
  • Rituximab-rixa
  • Rituximab-rixi
  • Riximyo
  • RTXM 83
  • RTXM-83
  • ABP-798
  • ABP798
  • CT P10
  • CTP10
  • GP 2013
  • GP-2013
  • GP2013
  • Rituximab Biosimilar GP2013
Procedure: Positron Emission Tomography
Undergo PET/CT
Other Names:
  • Medical Imaging, Positron Emission Tomography
  • PET
  • PET Scan
  • Positron Emission Tomography Scan
  • Positron-Emission Tomography
  • proton magnetic resonance spectroscopic imaging
  • PT
  • Positron emission tomography (procedure)
Procedure: Bone Marrow Biopsy
Undergo bone marrow biopsy and aspiration
Other Names:
  • Biopsy of Bone Marrow
  • Biopsy, Bone Marrow
Procedure: Computed Tomography
Undergo CT or PET/CT
Other Names:
  • CT
  • CAT
  • CAT Scan
  • Computed Axial Tomography
  • Computerized Axial Tomography
  • Computerized Tomography
  • CT Scan
  • tomography
  • Computerized axial tomography (procedure)
  • Computerized Tomography (CT) scan
Procedure: Bone Marrow Aspiration
Undergo bone marrow biopsy and aspiration

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Very good partial response or better (VGPR or better) rate
Time Frame: Up to 5 years
A Cochran-Mantel-Haenszel test will be performed to compare the VGPR or better rates in Arm 1 and Arm 2 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.
Up to 5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall response rate
Time Frame: Up to 5 years
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.
Up to 5 years
Incidence of adverse events
Time Frame: Up to 5 years
As assessed by Common Terminology Criteria for Adverse Events Version 5.0.
Up to 5 years
Progression-free survival
Time Frame: 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
Will be analyzed using the Kaplan-Meier method, and a stratified log-rank test will be performed to compare survival outcomes in the ibrutinib rituximab (IR) and venetoclax rituximab (VR) arms while controlling for the effects from the stratification factor of prior rituximab treatment.
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
Overall survival
Time Frame: From the date of registration to the date of death due to any cause, assessed up to 5 years
Will be analyzed using the Kaplan-Meier method, and a stratified log-rank test will be performed to compare survival outcomes in the IR and VR arms while controlling for the effects from the stratification factor of prior rituximab treatment.
From the date of registration to the date of death due to any cause, assessed up to 5 years
Rate of complete response
Time Frame: From the date of registration to the date of complete response, assessed up to 5 years
Will be analyzed using the cumulative incidence competing risks method.
From the date of registration to the date of complete response, assessed up to 5 years
Time to VGPR or better
Time Frame: Up to 5 years
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.
Up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Sikander Ailawadhi, SWOG Cancer Research Network

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 5, 2022

Primary Completion (Estimated)

March 31, 2028

Study Completion (Estimated)

March 31, 2028

Study Registration Dates

First Submitted

April 9, 2021

First Submitted That Met QC Criteria

April 9, 2021

First Posted (Actual)

April 12, 2021

Study Record Updates

Last Update Posted (Estimated)

January 10, 2025

Last Update Submitted That Met QC Criteria

January 9, 2025

Last Verified

December 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2021-02851 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • U10CA180888 (U.S. NIH Grant/Contract)
  • S2005 (Other Identifier: CTEP)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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