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Marginal Zone LymphomaPhase 3NCT04212013

A Study of Ibrutinib With Rituximab in People With Untreated Marginal Zone Lymphoma

A Phase 3 study testing Ibrutinib and Rituximab in people with Marginal Zone Lymphoma, run by Memorial Sloan Kettering Cancer Center at 10 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

The purpose of this study is to see if the combination of rituximab and ibrutinib can help people with marginal zone lymphoma who have not received treatment in the past. The study will also compare the combination of rituximab and ibrutinib with the combination of rituximab and placebo to see which combination works… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Marginal Zone Lymphoma
What is being tested?
Ibrutinib and Rituximab
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
23 participants
Where
10 sitesUnited States
Study dates
23 Dec 2019to 18 Mar 2027
Phase
Phase 3
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

  • Histologically documented marginal zone lymphoma, including splenic, nodal, and extranodal sub-types at the enrolling institution.
  • No prior systemic therapy for MZL with the exception of the following:
  • Prior antibiotic therapy for H. pylori, C. psittaci, and B. burgdorferi
  • Prior antiviral therapy for HCV Note: Subjects are eligible if they had prior splenectomy or other local surgical treatment or local radiation therapy without systemic therapy and now require their first ever systemic therapy.
  • Men and women ≥18 years of age
  • Patients with gastric MALT lymphoma must be H. pylori negative or have failed a trial of H. pylori eradication
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  • Patients with gastric MALT lymphoma who are H. pylori negative or who have relapsed/refractory disease after H. pylori eradication must be ineligible for, have refused or failed gastric radiation therapy
  • Eastern Cooperative Oncology Group (ECOG) performance status of ≤2
  • ≥1 measurable lesion on computed tomography (CT) scan (>1.5 cm in longest dimension) unless bone marrow disease only including those with hemolytic anemia. Lesions in anatomical locations (such as extremities or soft tissue lesions) that are not well visualized by CT may be measured by magnetic resonance imaging (MRI) instead. Patients with splenomegaly without other measurable disease must have splenomegaly of >15 cm in the craniocaudal direction
  • Life expectancy of >3 months, in the opinion of the investigator
  • Female subjects must be of non-reproductive potential (i.e., post-menopausal by history - no menses for ≥2 years; OR history of hysterectomy; OR history of bilateral tubal ligation; OR history of bilateral oophorectomy). Female subjects of childbearing potential must have a negative serum pregnancy test upon study entry
  • Male and female subjects who agree to use highly effective methods of birth control (e.g., condoms, implants, injectables, combined oral contraceptives, some intrauterine devices [IUDs], sexual abstinence, or sterilized partner) during the period of therapy and for 12 months (females) and 90 days (males) after the last dose of study drug
  • Documented evidence of need for treatment, including, but not limited to, threatened end-organ function, bulky disease (>5 cm), symptoms, requirement for transfusion or growth factor support, or medically significant need for intervention For subjects with presumptive evidence of transformation based on clinical assessment of factors such as, but not limited to, increasing lactate dehydrogenase (LDH), rapidly worsening disease, or frequent B-symptoms, both a pre-treatment tumor biopsy and bone marrow biopsy are required to rule out large cell transformation. For all subjects, results of both the tumor biopsy and bone marrow biopsy must be known prior to enrollment and randomization.

Who cannot join

  • Medically apparent central nervous system lymphoma or leptomeningeal disease
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible
  • History of other malignancies except adequately treated non-melanoma skin cancer, curatively treated in-situ cancer, or other solid tumors curatively treated with no evidence of disease for ≥2 years
  • Subject who received a strong cytochrome P450 (CYP) 3A inhibitor within 7 days prior to first dose of ibrutinib/placebo or subject who requires continuous treatment with a strong CYP3A inhibitor
  • Concurrent systemic immunosuppressant therapy (e.g., cyclosporine A, tacrolimus, etc., or chronic administration of >20 mg/day of prednisone) within 28 days of the first dose of study drug
  • Currently active, clinically significant cardiovascular disease such as uncontrolled arrhythmias or Class 3 or 4 congestive heart failure as defined by New York Heart Association Functional Classification; or a history of unstable angina, acute coronary syndrome, or myocardial infarction within 6 months of prior to screening
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  • Recent infection requiring systemic anti-infective treatment that was completed ≤14 days before the first dose of study drug
  • Any uncontrolled active systemic infection
  • Known bleeding diathesis (e.g., von Willebrand's disease) or hemophilia
  • Hepatitis B (HBV): All subjects must be screened for hepatitis B and C. Subjects with a positive polymerase chain reaction for hepatitis B must be on entecavir or equivalent therapy as per institutional standard of care. (Hep C patients may be enrolled if other parameters precluding hepatic impairment are met. And they are not undergoing active therapy for hepatitis C
  • Human immunodeficiency virus (HIV): NOTE: HIV is a contraindication if the subject has an active opportunistic infection (OI) within 12 months and CD4 count is below the normal range
  • Any of the following abnormalities:
  • Absolute neutrophil count (ANC) <750 cells/mm3 (0.75 x 10^9/L) unless there is documented bone marrow involvement
  • Platelet count <50,000 cells/mm^3 (50 x 10^9/L) independent of transfusion support unless there is documented bone marrow involvement
  • Serum aspartate transaminase (AST) or alanine transaminase (ALT) ≥3.0 x upper limit of normal (ULN)
  • Creatinine >2.0 x ULN or Estimated Glomerular Filtration Rate GFR [Cockcroft-Gault]) <30 mL/min
  • Hemoglobin <8.0 g/dL unless secondary to hemolysis or documented bone marrow involvement
  • Bilirubin >1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin)
  • PT/INR >1.5 x ULN and PTT (aPTT) >1.5 x ULN unless factor XI deficiency or lupus anticoagulant.
  • Unable to swallow capsules or disease significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, or complete bowel obstruction
  • Major surgery within 4 weeks prior to the first dose of study drug
  • Any life-threatening illness, medical condition, including uncontrolled diabetes mellitus (DM), or organ system dysfunction that, in the opinion of the investigator, could compromise the subject's safety or put the study outcomes at undue risk
  • Lactating or pregnant
  • Unwilling or unable to participate in all required study evaluations and procedures
  • Unable to understand the purpose and risks of the study and to provide a signed and dated informed consent form (ICF) and authorization to use protected health information (in accordance with national and local subject privacy regulations)
  • Subjects with chronic liver disease with hepatic impairment Child-Pugh class B or C

Trial locations and contacts

10 sites in 1 country.

10 sites in 1 country

United States10 sites

  • Memorial Sloan Kettering Basking Ridge

    Basking Ridge, New Jersey, 07920

  • Memorial Sloan Kettering Commack

    Commack, New York, 11725

  • Memorial Sloan Kettering Westchester

    Harrison, New York, 10604

  • Memorial Sloan Kettering Monmouth

    Middletown, New Jersey, 07748

  • Memorial Sloan Kettering Bergen

    Montvale, New Jersey, 07645

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Mayo Clinic Cancer Center

    Rochester, Minnesota, 55905

  • Moffitt Cancer Center

    Tampa, Florida, 33612

  • Memorial Sloan Kettering Nassau

    Uniondale, New York, 11553

  • George Washington Cancer Center

    Washington D.C., District of Columbia, 20037

Other trials in United States

About this study

Official title: A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase III Study of Ibrutinib in Combination With Rituximab in Subjects With Treatment Naïve Marginal Zone Lymphoma

The purpose of this study is to see if the combination of rituximab and ibrutinib can help people with marginal zone lymphoma who have not received treatment in the past. The study will also compare the combination of rituximab and ibrutinib with the combination of rituximab and placebo to see which combination works better.

Being tested
Ibrutinib, Rituximab, Placebo
Keywords
Ibrutinib, Rituximab, Treatment Naïve, 19-243
Medical subject headings
Lymphoma, B-Cell, Marginal Zone

What participants receive

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

  • IbrutinibDrug

    Ibrutinib capsules (140 mg each) will be dosed at 560 mg once daily on a 28-day cycle on a continuous basis.

  • RituximabDrug

    Will receive rituximab: 375 mg/m^2 on days 1, 8, 15 and 22 of cycle 1

  • PlaceboOther

    Placebo capsules will be similarly dosed at 4 capsules daily.

Study groups in NCT04212013
Study groupRoleWhat they receive
Ibrutinib/RituximabExperimentalAll subjects meeting eligibility criteria will receive rituximab: 375 mg/m^2 on days 1, 8, 15 and 22 on cycle 1.
Receives: Drug: Ibrutinib; Drug: Rituximab
Ibrutinib/PlaceboPlacebo comparatorIbrutinib capsules (140 mg each) will be dosed at 560 mg once daily on a 28-day cycle on a continuous basis. Placebo capsules will be similarly dosed at 4 capsules daily.
Receives: Drug: Ibrutinib; Other: Placebo

What is being measured

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

  1. complete response

    per the RECIL criteria

    Measured: 30 months after randomization

Timeline

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

  1. First posted26 Dec 2019
  2. Study start23 Dec 2019
  3. Primary completion18 Mar 2027 (estimated)
  4. Study completion18 Mar 2027 (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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
This is a Phase III randomized, double-blind, placebo controlled, multicenter.
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
23 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04212013
Sponsor's protocol ID
19-243
Status last verified
Jul 2026
First submitted
23 Dec 2019
Last updated
23 Jul 2026
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Ibrutinib and Rituximab in people with Marginal Zone Lymphoma, run by Memorial Sloan Kettering Cancer Center at 10 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 13 inclusion and 26 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: under way, not looking for participants, as of the sponsor's last update on 23 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

complete response (time frame: 30 months after randomization). 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 NCT04212013.

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 23 Jul 2026.

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