New hope for marginal zone lymphoma: Chemo-Free combo shows promise

NCT ID NCT03697512

Disease control Sponsor: International Extranodal Lymphoma Study Group (IELSG) Source: ClinicalTrials.gov ↗

First seen Jun 27, 2026 · Last updated Jun 27, 2026

Summary

This phase II trial tests a combination of two drugs, ibrutinib and rituximab, in people with untreated marginal zone lymphoma, a rare blood cancer. The study aims to see how many patients achieve complete remission after one year and how long they stay cancer-free. About 175 participants will receive the treatment, and researchers will also monitor side effects closely.

What this could mean

Our plain-language read of the trial. This is informational only, not medical advice or a prediction.

Active substance: ibrutinib and rituximab
What this could lead to: If successful, this combination could offer a new first-line treatment option for marginal zone lymphoma, potentially improving long-term disease control without chemotherapy.
What could go wrong: This is a single-arm phase II trial with no placebo group, so results are preliminary. Side effects from ibrutinib and rituximab can include infections, bleeding, and infusion reactions.

This is an AI summary of the original study and may miss details. Read our disclaimer.

Study facts

What this study's own registry entry says, in plain language.

Phase

Phase 2

Tests whether the treatment actually works, and watches for side effects, in a larger group.

Participants

175 people

The number who actually took part.

Started

Sep 2019

Expected to finish

Jun 2027

An estimate. End dates often move.

Lead sponsor

Other sponsor

The registry's catch-all category, for sponsors it does not file as a company, a government agency, or a research network.

Who can take part

This study's own entry requirements. Only the study team can say for certain whether you qualify.

Ages

18 years and older

Sex

Anyone

Healthy volunteers

Not accepted

This study is not open to healthy volunteers. The entry requirements below say who it is open to.

Show the full entry requirements

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: Chemotherapy and immunotherapy-naïve, symptomatic and in need of treatment patients, with histologically proven CD20-positive MZL, not eligible for local therapy, including: 1. EMZL (MALT Lymphoma) patients with MALT- IPI score 1-2 in need of systemic therapy. Either de novo or relapsed following local therapy (including surgery, radiotherapy and antibiotics for H. pylori-positive gastric lymphoma) arisen at any extranodal site with MALT-international prognostic index (IPI) score 1-2 at the time of study entry. 1.1.The following patients with gastric MALT Lymphoma can be entered: 1. H. pylori-negative cases, either de novo (non pretreated) or at relapse following local therapy (i.e., surgery, radiotherapy or antibiotics). 2. H. pylori-positive cases at diagnosis, who either first line antibiotics or further local treatment (surgery or radiotherapy), including patients with: * clinical (endoscopic) and histological evidence of disease progression at any time post H. pylori eradication; * clinical (endoscopic) and histological relapse (without H. pylori re-infection), after a remission patients; * persistent (stable) lymphoma at ≥ 1 year post H. pylori eradication. 1.2. Similar consideration may be applied to patients with ocular adnexal lymphoma treated with antibiotics. 2. SMZL patients in need of therapy. Either de novo or relapsed following local therapy \[including surgery and antiviral therapy for Hepatitis C virus (HCV)\]. Patient must have a symptomatic disease requiring treatment and be not eligible for splenectomy or not willing to undergo splenectomy. 2.1. Patients with SMZL can be entered if any of the following criteria is present: 1. bulky progressive or painful splenomegaly; 2. enlarged lymph nodes or involvement of extranodal sites with or without cytopenias , i.e. involvement of ≥3 nodal sites, each with a diameter of ≥3 cm. Any nodal tumor mass with a diameter of ≥7 cm (GELG criteria, as adopted in follicular lymphoma); 3. one of the following symptomatic/progressive cytopenias: * Hgb \< 10 g/dL; * ANC \< 1000/μL: * PLT\< 80 000/μL whatever the reason (autoimmune or hypersplenism or bone marrow infiltration). 2.2. Splenectomised patients with rapidly raising lymphocyte counts, lymphadenopathy or involvement of extranodal sites can be entered. 2.3. SMZL with concomitant HCV infection who have not responded to or are relapsed after antiviral therapy can be entered. 3. NMZL patients in need of therapy Either, de novo presenting with disseminated disease or relapsed after local radiotherapy or following antiviral therapy for HCV. Localized nodal MZL is not eligible. * Measurable or evaluable disease. * Ann Arbor II-IV. Stage I disease may be eligible only if not candidate to local therapy (surgery or radiotherapy). * Age ≥ 18. * Life expectancy of at least 1 year. * ECOG Performance status 0-2. * Adequate bone marrow, kidney and liver function * For women of childbearing potential only: negative serum pregnancy test done within 7 days prior to study drugs administration or within 14 days if with a confirmatory urine pregnancy test within 7 days prior to the first study drugs administration. * Fertile male or female patients of childbearing potential and their partners must use higly effective contraception methods during the study and for at least 12 months after the last dose of subcutaneous rituximab. In case hormonal methods of birth control is used a barrier method must be added. * Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: 1. Any type of lymphoma other than MZL (including MZL with histologic transformation to high-grade lymphoma). 2. Localized (stage IE and IIE) MALT lymphoma, for example gastric, ocular and cutaneous lymphoma, that may benefit from local therapy only (surgery or radiotherapy). 3. Known CNS involvement of MZL. 4. Any previous systemic treatment with immunotherapy or chemotherapy or with BTK inhibitors. 5. Major surgery within 4 weeks prior to registration. 6. History of stroke or intracranial bleeding within 6 months. 7. Known bleeding diathesis (eg, von Willebrand's disease) or hemophilia. 8. Concurrent use of warfarin of other vitamin K antagonists. 9. Concurrent use of strong cytochrome P450 (CYP)3A4/5 inhibitors (see http://medicine.iupui.edu/clinpharm/ddis/clinical-table/). 10. Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue risk. 11. International normalized ratio (INR) or prothrombin time (PT) ≥1.5 ULN. Partial thromboplastin time (PTT) or activated PTT (aPTT) ≥1.5 ULN unless due to lupus anticoagulant. 12. Vaccinated with live, attenuated vaccines within 4 weeks prior to randomization. 13. Clinically significant hypersensitivity (e.g., anaphylactic or anaphylactoid reactions to the compound of ibrutinib and/or rituximab themselves or to the excipients in their formulation). 14. Positive test results for chronic HBV infection (defined as positive HBsAg serology). 15. Patients with occult or prior HBV infection (defined as negative HBsAg and positive total HBcAb) may be included if HBV DNA is undetectable, provided that they are willing to undergo monthly DNA testing and taking specific antiviral prophylaxis, according to local policy. Patients who have protective titers of hepatitis B surface antibody (HBsAb) after vaccination are eligible. 16. Positive test results for hepatitis C. Patients positive for HCV antibody are eligible only if PCR is negative for HCV RNA. 17. HIV infection or immunodeficiency. 18. Active, severe infections 19. Pregnancy or breastfeeding. 20. Clinically significant cardiovascular diseases such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification. 21. Any serious medical or psychiatric illness likely to interfere with participation in this clinical study. 22. Prior history of malignancies other than MZL within 3 years,with the exception of adequately treated cervical carcinoma in situ or localized non-melanoma skin cancer. 23. Current enrolment or participation in another therapeutic clinical trial within 28 days prior to treatment start

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Conditions

The condition(s) this trial relates to.

Lymphoma, B-Cell, Marginal Zone MALT lymphoma marginal zone lymphoma nodal marginal zone B-cell lymphoma splenic marginal zone lymphoma

As listed by the trial registrant

The condition terms exactly as the trial's registrant entered them.

Marginal zone lymphoma Nodal marginal zone lymphoma Splenic marginal zone lymphoma

Contacts and locations

Locations

A.O. Spedali Civili di Brescia

Brescia, 25123, Italy
A.O.U. Città della Salute e della Scienza di Torino Ospedale Molinette

Torino, TO, 10126, Italy
AAST Grande Ospedale Metropolitano Niguarda

Milan, 20162, Italy
Azienda Ospedaliera Arcispedale Santa Maria Nuova IRCCS

Reggio Emilia, 42123, Italy
Azienda Ospedaliera Universitaria Ospedali Riuniti - Università Politecnica delle Marche

Ancona, 60100, Italy
Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI)

Trieste, Italy
CHRU de Strasbourg

Strasbourg, 67091, France
CHU Dijon Bourgogne - Hôpital François Mitterand

Dijon, 21000, France
CHU UCL Namur / site Godinne

Yvoir, B5530, Belgium
CHU d'Estaing

Clermont-Ferrand, Cedex 1, 63003, France
CHU de Grenoble - Hôpital Albert MICHALLON

La Tronche, 38700, France
CHU de Montpellier

Montpellier, Cedex 05, 34295, France
CHU de Nancy - Hôpital Brabois

Vandœuvre-lès-Nancy, 54500, France
CHU de Rennes Pontchaillou

Rennes, Cedex 9, 35033, France
CHU de Tours - Hôpital Bretonneau

Tours, Cedex 01, 37004, France
Centre Hospitalier Lyon Sud

Pierre-Bénite, 69495, France
Fondazione IRCCS - Cà Granda - Ospedale Maggiore Policlinico

Milan, 20122, Italy
Fondazione IRCCS - Istituto Nazionale dei Tumori

Milan, 20133, Italy
Fondazione IRCCS - Policlinico San Matteo

Pavia, 27100, Italy
Giovanni Paolo II/I.R.C.C.S. Istituto Tumori

Bari, 70124, Italy
Hôpitaux Universitaires de Genève

Geneva, 1211, Switzerland
IHBN - CHU Côte de Nacre

Caen, 14033, France
IUCT Oncopole Toulouse

Toulouse, 31100, France
Inselspital Bern

Bern, 3010, Switzerland
Institut Bergonié

Bordeaux, 33076, France
Instituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E.

Lisbon, 1099-023, Portugal
Istituto Oncologico della Svizzera Italiana (IOSI)

Bellinzona, Canton Ticino, 6500, Switzerland
Kantonalspital Baden

Baden, 5404, Switzerland
Ospedale Oncologico Businco

Cagliari, 09121, Italy
Ospedale San Raffaele

Milan, MI, 20132, Italy
Ospedale degli Infermi

Ponderano, BI, 13875, Italy
Ospedale di Circolo e Fondazione Macchi di Varese

Varese, 21100, Italy
Saint Louis Hospital

Paris, 75010, France
U.O. Ematologia AUSL Ravenna

Ravenna, 48121, Italy
Università degli Studi di Roma La Sapienza

Roma, 00185, Italy
Universitätsspital Zürich

Zurich, 8091, Switzerland

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