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

MALT Lymphoma Clinical Trial

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01808599
• Other study ID #: IELSG38
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: December 2013
• Est. completion date: September 2028

Study information

• Verified date: May 2023
• Source: International Extranodal Lymphoma Study Group (IELSG)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 112
• Est. completion date: September 2028
• Est. primary completion date: March 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, B-Cell, Marginal Zone
• Lymphoma, Non-Hodgkin
• MALT Lymphoma
• Stomach Neoplasms

Intervention

Drug:
• Chlorambucil

• Rituximab i.v.

• Rituximab s.c.

Locations

Country	Name	City	State
France	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
Italy	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	Milano
Italy	Milano Ospedale Policlinico	Milano
Italy	Nocera	Nocera Umbra
Italy	IOV Padova	Padova
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
Switzerland	IOSI - Oncology Institute of Southern Switzerland	Bellinzona

Sponsors (1)

Lead Sponsor	Collaborator
International Extranodal Lymphoma Study Group (IELSG)

Countries where clinical trial is conducted

France,  Italy,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete remission rate		week 25
Secondary	Response Rate	Response rate (Complete and partial remission rates) for all patients	week 25
Secondary	Event-free-survival (EFS)		at 5 years