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

NCT ID: NCT01808599

Last Updated: 2026-01-15

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 112 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-12-31
• Study Completion Date: 2028-09-30

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).

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

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).

Group Type: EXPERIMENTAL

Chlorambucil

Intervention Type: DRUG

Rituximab i.v.

Intervention Type: DRUG

Rituximab s.c.

Intervention Type: DRUG

Interventions

Chlorambucil

Intervention Type: DRUG

Rituximab i.v.

Intervention Type: DRUG

Rituximab s.c.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. 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.

2. 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.

3. Any stage (Ann Arbor I-IV) (see Appendix A)

4. Age ≥ 18

5. Life expectancy of at least 1 year

6. ECOG performance status 0-2 (see Appendix B)

7. Adequate bone marrow function (WBC >3.0x109/L, ANC >1.5x109/L, PLT >100x109/L), unless due to lymphoma involvement

8. 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

9. 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

10. 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

11. Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

1. Evidence of histologic transformation to a high grade lymphoma

2. Prior diagnosis of neoplasm within 5 years, except cervical intraepithelial neoplasia type 1 (CIN1) or localized non-melanomatous skin cancer

3. Prior chemotherapy

4. Prior immunotherapy with any anti-CD20 monoclonal antibody

5. Prior radiotherapy in the last 6 weeks

6. 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

7. 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

8. Evidence of symptomatic central nervous system (CNS) disease

9. Evidence of active opportunistic infections

10. Known HIV infection

11. 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

12. Positive serology for hepatitis C (HC) defined as a positive test for HCAb, confirmed by HC RIBA immunoblot assay on the same sample.

13. Pregnant or lactating status

14. 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

15. 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

International Extranodal Lymphoma Study Group (IELSG)

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Emanuele Zucca, MD

Role: PRINCIPAL_INVESTIGATOR

IOSI Oncology Institute of Southern Switzerland

Locations

Créteil Hopital Henri Mondor

Créteil, , France

Dijon CHU Hopital le Bocage

Dijon, , France

Clermont Ferrand CHU Estaing

Estaing, , France

Grenoble CHU Pontchaillou

Grenoble, , France

Lille CHRU Hopital Claude Dieu

Lille, , France

Pierre Bénite CHU Lyon Sud

Lyon, , France

Marseille Paoli Calmettes

Marseille, , France

Montpellier CHU Saint Eloi

Montpellier, , France

Vandoeuvre lès Nancy CHU Brabois

Nancy, , France

Nantes CHU Hotel Dieu

Nantes, , France

Paris Hopital Saint Louis

Paris, , France

Rennes CHU Pontchaillou

Rennes, , France

Rouen Centre Henri Becquerel

Rouen, , France

Tours CHU Bretonneau

Tours, , France

AO SS. Antonio e Biagio e Cesare Arrigo

Alessandria, , Italy

Ancona

Ancona, , Italy

Centro di Riferimento Oncologico di Aviano

Aviano, , Italy

Biella Ospedale degli Infermi

Biella, , Italy

Ematologia e CTMO Ospedale Bolzano

Bolzano, , Italy

Ematologia Ospedale Businco (Cagliari)

Cagliari, , Italy

ARNAS Garibaldi Catania

Catania, , Italy

Genova Ematologia I H San Martino

Genova, , Italy

Azienda Sanitaria AUSL6 Livorno

Livorno, , Italy

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

Meldola, , Italy

Istituto Nazionale dei Tumori, Milano

Milan, , Italy

Milano Ospedale Policlinico

Milan, , Italy

Nocera

Nocera Umbra, , Italy

IOV Padova

Padua, , Italy

Azienda Ospedaliero-Universitaria di Parma

Parma, , Italy

UO Ematologia Ravenna

Ravenna, , Italy

Arcispedale Santa Maria Nuova, Azienda Ospedaliera di Reggio Emilia

Reggio Emilia, , Italy

Ospedale Infermi Ematologia Rimini

Rimini, , Italy

IRCCS/CROB Rionero in Vulture

Rionero in Vulture, , Italy

Istituto Regina Elena, Roma, IFO

Roma, , Italy

SC Oncoematologia Terni

Terni, , Italy

SC Ematologia Torino-Molinette

Torino, , Italy

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

Torino, , Italy

IOSI - Oncology Institute of Southern Switzerland

Bellinzona, , Switzerland

Countries

France; Italy; Switzerland

References

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.

Reference Type: DERIVED

PMID: 38385243 (View on PubMed)

Other Identifiers

IELSG38

Identifier Type: -

Identifier Source: org_study_id