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MALT LymphomaPhase 2NCT01808599

Phase II Study of Chlorambucil and Subcutaneous Rituximab in Patients With Extranodal MALT Lymphoma

A Phase 2 study testing Chlorambucil, Rituximab i.v. and Rituximab s.c. in people with MALT Lymphoma, run by International Extranodal Lymphoma Study Group (IELSG) at 38 sites in 3 countries.

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

Single arm phase II study of Chlorambucil in combination with subcutaneous Rituximab followed by maintenance therapy with subcutaneous Rituximab in patients with histologically proven diagnosis of CD20-positive marginal zone B-cell lymphoma of MALT type arisen at any extranodal site, either de novo, or relapsed… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
MALT Lymphoma
What is being tested?
Chlorambucil, Rituximab i.v. and Rituximab s.c.
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
112 participants
Where
38 sitesin 3 countries
Study dates
Dec 2013to Sep 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

  • Histologically proven diagnosis of CD20-positive marginal zone B-cell lymphoma of MALT type either de novo, or relapsed following local therapy (including surgery, radiotherapy and antibiotics for H. pylori-positive gastric lymphoma) arisen at any extranodal site 1.1 The following patients with gastric MALT Lymphoma can be entered:
  • H. pylori-negative cases, either de novo (non pre-treated) or at relapse following local therapy (i.e., surgery, radiotherapy or antibiotics).
  • H. pylori-positive cases at diagnosis, who failed antibiotic therapy, including
  • Patients with clinical (endoscopic) and histological evidence of disease progression at any time post H. pylori eradication
  • Stable disease with persistent lymphoma at ≥ 1 year post H. pylori eradication
  • Relapse (without H. pylori re-infection), after a remission
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  • Patients who failed either first line antibiotics or further local treatment (surgery or radiotherapy) 1.2 Similar consideration may be applied to patients with ocular adnexal lymphoma treated with antibiotics.
  • Measurable or evaluable disease. Measurable disease in at least two perpendicular dimensions on an imaging scan is defined as: lymph node or nodal mass bi-dimensional measurement with > 1.5 cm in longest transverse diameter or the short diameter must measure > 10 mm regardless of the longest transverse diameter.
  • Any stage (Ann Arbor I-IV) (see Appendix A)
  • Age ≥ 18
  • Life expectancy of at least 1 year
  • ECOG performance status 0-2 (see Appendix B)
  • Adequate bone marrow function (WBC >3.0x109/L, ANC >1.5x109/L, PLT >100x109/L), unless due to lymphoma involvement
  • Adequate kidney (serum creatinine <1,5x upper normal) and liver function (ASAT/ALAT <2,5 upper normal, total bilirubin <2,5x upper normal), unless due to lymphoma involvement
  • 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 two forms of contraception during the study and for at least 12 months after the last dose of subcutaneous rituximab.
  • For appropriate methods of contraception considered acceptable, see Appendix C. Should a woman become pregnant or suspect she is pregnant while she or her partner are participating in this study and for 12 months after study participation, the patient should inform the treating physician immediately.
  • Female patients of childbearing potential are defined as follows:
  • Pre-menopausal women (patients with regular menstruation, patients after menarche with amenorrhea or irregular cycles, patients using a contraceptive method that precludes withdrawal bleeding
  • Women who have had tubal ligation
  • Female patients may be considered to NOT be of childbearing potential for the following reasons:
  • The patient has undergone total abdominal hysterectomy with bilateral salpingo-oophorectomy or bilateral oophorectomy
  • The patient is medically confirmed to be menopausal (no menstrual period) for 24 consecutive months
  • Ability to understand and the willingness to sign a written informed consent document

Who cannot join

  • Evidence of histologic transformation to a high grade lymphoma
  • Prior diagnosis of neoplasm within 5 years, except cervical intraepithelial neoplasia type 1 (CIN1) or localized non-melanomatous skin cancer
  • Prior chemotherapy
  • Prior immunotherapy with any anti-CD20 monoclonal antibody
  • Prior radiotherapy in the last 6 weeks
  • Use of corticosteroids during the last 28 days, unless prednisone chronically administered at a dose <20 mg/day for indications other than lymphoma or lymphoma-related symptoms
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  • Evidence of clinically significant cardiac disease, as defined by history of symptomatic ventricular arrhythmias, congestive heart failure or myocardial infarction within 12 months before study entry
  • Evidence of symptomatic central nervous system (CNS) disease
  • Evidence of active opportunistic infections
  • Known HIV infection
  • Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg. In addition, if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a HBV DNA test will be performed and if positive the subject will be excluded
  • Positive serology for hepatitis C (HC) defined as a positive test for HCAb, confirmed by HC RIBA immunoblot assay on the same sample.
  • Pregnant or lactating status
  • Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
  • Fertile men or women of childbearing potential who do not agree to use a highly effective measure of contraception (such as oral contraceptives, intrauterine device or barrier method of contraception in conjunction with spermicidal jelly or surgically sterile) throughout the study and for at least 12 months after the last dose of subcutaneous rituximab

Trial locations and contacts

38 sites in 3 countries.

38 sites in 3 countries

Italy23 sites

  • AO SS. Antonio e Biagio e Cesare Arrigo

    Alessandria

  • Ancona

    Ancona

  • Centro di Riferimento Oncologico di Aviano

    Aviano

  • Biella Ospedale degli Infermi

    Biella

  • Ematologia e CTMO Ospedale Bolzano

    Bolzano

  • Ematologia Ospedale Businco (Cagliari)

    Cagliari

  • ARNAS Garibaldi Catania

    Catania

  • Genova Ematologia I H San Martino

    Genova

  • Azienda Sanitaria AUSL6 Livorno

    Livorno

  • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola

    Meldola

  • Istituto Nazionale dei Tumori, Milano

    Milan

  • Milano Ospedale Policlinico

    Milan

  • Nocera

    Nocera Umbra

  • IOV Padova

    Padova

  • Azienda Ospedaliero-Universitaria di Parma

    Parma

  • UO Ematologia Ravenna

    Ravenna

  • Arcispedale Santa Maria Nuova, Azienda Ospedaliera di Reggio Emilia

    Reggio Emilia

  • Ospedale Infermi Ematologia Rimini

    Rimini

  • IRCCS/CROB Rionero in Vulture

    Rionero in Vulture

  • Istituto Regina Elena, Roma, IFO

    Roma

  • SC Oncoematologia Terni

    Terni

  • SC Ematologia Torino-Molinette

    Torino

  • Torino Università, Ematologia 1, AO Città della Salute e della Scienza

    Torino

Other trials in Italy

France14 sites

  • Créteil Hopital Henri Mondor

    Créteil

  • Dijon CHU Hopital le Bocage

    Dijon

  • Clermont Ferrand CHU Estaing

    Estaing

  • Grenoble CHU Pontchaillou

    Grenoble

  • Lille CHRU Hopital Claude Dieu

    Lille

  • Pierre Bénite CHU Lyon Sud

    Lyon

  • Marseille Paoli Calmettes

    Marseille

  • Montpellier CHU Saint Eloi

    Montpellier

  • Vandoeuvre lès Nancy CHU Brabois

    Nancy

  • Nantes CHU Hotel Dieu

    Nantes

  • Paris Hopital Saint Louis

    Paris

  • Rennes CHU Pontchaillou

    Rennes

  • Rouen Centre Henri Becquerel

    Rouen

  • Tours CHU Bretonneau

    Tours

Other trials in France

Switzerland1 site

  • IOSI - Oncology Institute of Southern Switzerland

    Bellinzona, 6500

Other trials in Switzerland

About this study

Official title: A Phase II Study of Chlorambucil in Combination With Subcutaneous Rituximab Followed by Maintenance Therapy With Subcutaneous Rituximab in Patients With Extranodal Marginal Zone B-cell Lymphoma of Mucosa Associated Lymphoid Tissue (MALT Lymphoma)

Single arm phase II study of Chlorambucil in combination with subcutaneous Rituximab followed by maintenance therapy with subcutaneous Rituximab in patients with histologically proven diagnosis of CD20-positive marginal zone B-cell lymphoma of MALT type arisen at any extranodal site, either de novo, or relapsed following local therapy (including surgery, radiotherapy and antibiotics for H. pylori-positive gastric lymphoma).

Read the detailed description

The study consists in three parts. In Part A (induction phase I) patients will be treated with Chlorambucil 6 mg/m2 daily p.o for 42 consecutive days (weeks 1-6) in combination with intravenous Rituximab 375mg/m2 on day 1 week 1 followed by subcutaneous Rituximab 1400mg on days 8, 15 and 22 (day 1 of weeks 2, 3 and 4). After restaging (CT scan to be performed during weeks 7-8, i.e. between d42 and d55), responding patients (CR, CRu, PR) and those with stable disease will be treated in part B (induction phase II). In part B, starting from d56, (month 3) patients will receive Chlorambucil 6 mg/m2 daily p.o for 14 consecutive days (d1-14) every 28 days for 4 cycles in combination with subcutaneous Rituximab 1400mg on day 1 of each 28-day cycle. After restaging (CT scan to be performed at the end of month 6) responding patients and those with stable disease will be treated in part C. In Part C (maintenance phase) patients will be treated with subcutaneous Rituximab 1400mg every two months for 2 years (in total 12 injections). During maintenance phase, CT scans will be performed every 12 months and patients responding or with stable disease will stay on treatment for a total of two years as above reported.

Conditions
MALT Lymphoma
Being tested
Chlorambucil, Rituximab i.v., Rituximab s.c.
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.

  • ChlorambucilDrug

  • Rituximab i.v.Drug

  • Rituximab s.c.Drug

Study groups in NCT01808599
Study groupRoleWhat they receive
Chlorambucil, Rituximab i.v., Rituximab s.c.ExperimentalChlorambucil 6 mg/m2 daily p.o for 42 consecutive days (weeks 1-6) in combination with intravenous Rituximab 375mg/m2 on days 1, 8, 15 and 22 (day 1 of weeks 1, 2, 3 and 4). Starting from d56, (month 3) patients will receive Chlorambucil 6 mg/m2 daily p.o for 14 consecutive days (d1-14) every 28 days for 4 cycles in combination with subcutaneous Rituximab 1400mg on day 1 of each 28-day cycle. Therefore subcutaneous Rituximab 1400mg every two months for 2 years (in total 12 injections).
Receives: Drug: Chlorambucil; Drug: Rituximab i.v.; Drug: Rituximab s.c.

What is being measured

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

  1. Complete remission rate

    Measured: week 25

Secondary outcomes (2)

  1. Response Rate

    Response rate (Complete and partial remission rates) for all patients

    Measured: week 25

  2. Event-free-survival (EFS)

    Measured: at 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 posted11 Mar 2013 (estimated)
  2. Study startDec 2013
  3. Primary completionMar 2016
  4. Study completionSep 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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
112 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01808599
Sponsor's protocol ID
IELSG38
Status last verified
Jan 2026
First submitted
6 Mar 2013
Last updated
15 Jan 2026
Results posted
No
Data monitoring committee
No

Publications

  • Stathis A, Pirosa MC, Orsucci L, Feugier P, Tani M, Ghesquieres H, Musuraca G, Rossi FG, Merli F, Guieze R, Gyan E, Gini G, Marino D, Gressin R, Morschhauser F, Cavallo F, Palombi F, Conconi A, Tessoulin B, Tilly H, Zanni M, Cabras MG, Capochiani E, Califano C, Celli M, Pulsoni A, Angrilli F, Occhini U, Casasnovas RO, Cartron G, Devizzi L, Haioun C, Liberati AM, Houot R, Merli M, Pietrantuono G, Re F, Spina M, Landi F, Cavalli F, Bertoni F, Rossi D, Ielmini N, Borgo E, Luminari S, Zucca E, Thieblemont C. IELSG38: phase II trial of front-line chlorambucil plus subcutaneous rituximab induction and maintenance in mucosa-associated lymphoid tissue lymphoma. Haematologica. 2024 Aug 1;109(8):2564-2573. doi: 10.3324/haematol.2023.283918.

    PubMed 38385243

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Chlorambucil, Rituximab i.v. and Rituximab s.c. in people with MALT Lymphoma, run by International Extranodal Lymphoma Study Group (IELSG) at 38 sites in 3 countries.

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 24 inclusion and 15 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 15 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 38 sites in Italy, France, Switzerland. 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?

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 remission rate (time frame: week 25). 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 NCT01808599, which also lists 1 linked publication.

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 15 Jan 2026.

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