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

NCT01808599 | Active Not Recruiting Phase 2

• 1 other identifier: IELSG38
• Study Type: interventional
• Target: 112
• Locations: 3 countries
• Sites: 38

Brief 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 following local therapy (including surgery, radiotherapy and antibiotics for H. pylori-positive gastric lymphoma).

Conditions

MALT Lymphoma

Outcome Measures

Primary Outcomes (1)

• Complete remission rate

  week 25

Secondary Outcomes (2)

• Response Rate

  week 25

• Event-free-survival (EFS)

  at 5 years

Study Arms (1)

Chlorambucil, Rituximab i.v., Rituximab s.c.

EXPERIMENTAL

Chlorambucil 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).

Drug: Chlorambucil; Drug: Rituximab i.v.; Drug: Rituximab s.c.

Interventions

Chlorambucil DRUG

Chlorambucil, Rituximab i.v., Rituximab s.c.

Rituximab s.c. DRUG

Chlorambucil, Rituximab i.v., Rituximab s.c.

Rituximab i.v. DRUG

Chlorambucil, Rituximab i.v., Rituximab s.c.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• International Extranodal Lymphoma Study Group (IELSG): lead

Study Sites (38)

Créteil Hopital Henri Mondor

Créteil, France

Location

Dijon CHU Hopital le Bocage

Dijon, France

Location

Clermont Ferrand CHU Estaing

Estaing, France

Location

Grenoble CHU Pontchaillou

Grenoble, France

Location

Lille CHRU Hopital Claude Dieu

Lille, France

Location

Pierre Bénite CHU Lyon Sud

Lyon, France

Location

Marseille Paoli Calmettes

Marseille, France

Location

Montpellier CHU Saint Eloi

Montpellier, France

Location

Vandoeuvre lès Nancy CHU Brabois

Nancy, France

Location

Nantes CHU Hotel Dieu

Nantes, France

Location

Paris Hopital Saint Louis

Paris, France

Location

Rennes CHU Pontchaillou

Rennes, France

Location

Rouen Centre Henri Becquerel

Rouen, France

Location

Tours CHU Bretonneau

Tours, France

Location

AO SS. Antonio e Biagio e Cesare Arrigo

Alessandria, Italy

Location

Ancona

Ancona, Italy

Location

Centro di Riferimento Oncologico di Aviano

Aviano, Italy

Location

Biella Ospedale degli Infermi

Biella, Italy

Location

Ematologia e CTMO Ospedale Bolzano

Bolzano, Italy

Location

Ematologia Ospedale Businco (Cagliari)

Cagliari, Italy

Location

ARNAS Garibaldi Catania

Catania, Italy

Location

Genova Ematologia I H San Martino

Genova, Italy

Location

Azienda Sanitaria AUSL6 Livorno

Livorno, Italy

Location

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

Meldola, Italy

Location

Istituto Nazionale dei Tumori, Milano

Milan, Italy

Location

Milano Ospedale Policlinico

Milan, Italy

Location

Nocera

Nocera Umbra, Italy

Location

IOV Padova

Padua, Italy

Location

Azienda Ospedaliero-Universitaria di Parma

Parma, Italy

Location

UO Ematologia Ravenna

Ravenna, Italy

Location

Arcispedale Santa Maria Nuova, Azienda Ospedaliera di Reggio Emilia

Reggio Emilia, Italy

Location

Ospedale Infermi Ematologia Rimini

Rimini, Italy

Location

IRCCS/CROB Rionero in Vulture

Rionero in Vulture, Italy

Location

Istituto Regina Elena, Roma, IFO

Roma, Italy

Location

SC Oncoematologia Terni

Terni, Italy

Location

SC Ematologia Torino-Molinette

Torino, Italy

Location

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

Torino, Italy

Location

IOSI - Oncology Institute of Southern Switzerland

Bellinzona, 6500, Switzerland

Location

Related Publications (1)

• 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.

  PMID: 38385243 DERIVED

MeSH Terms

Conditions

Lymphoma, B-Cell, Marginal Zone

Interventions

Chlorambucil

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals

Study Officials

• Emanuele Zucca, MD

  IOSI Oncology Institute of Southern Switzerland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2013
• First Posted: March 11, 2013
• Study Start: December 1, 2013
• Primary Completion: March 1, 2016
• Study Completion (Estimated): September 1, 2028
• Last Updated: January 15, 2026

Record last verified: 2026-01

Locations

FR (14); CH (1); IT (23)