Randomized Trial of Chlorambucil Versus Chlorambucil Plus Rituximab Versus Rituximab in MALT Lymphoma

Lymphoma, Mucosa-Associated Lymphoid Tissue Clinical Trial

Official title:

Multicenter Randomized Trial of Chlorambucil Versus Chlorambucil Plus Rituximab Versus Rituximab in Extranodal Marginal Zone B-cell Lymphoma of Mucosa Associated Lymphoid Tissue (MALT Lymphoma)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00210353
• Other study ID #: IELSG19
• Status: Completed
• Phase: Phase 3
• Start date: January 2003
• Est. completion date: February 17, 2016

Study information

• Verified date: October 2018
• Source: International Extranodal Lymphoma Study Group (IELSG)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Assess the therapeutic activity and safety of the combination of Chlorambucil and Rituximab in MALT lymphomas and determine whether the addition of Rituximab to Chlorambucil will improve the outcome of MALT lymphoma in comparison to treatment with Chlorambucil alone.

In April 2006, a third arm of treatment was added to compare the antitumor activity and safety of rituximab alone vs chlorambucil alone

Recruitment information / eligibility

• Status: Completed
• Enrollment: 454
• Est. completion date: February 17, 2016
• Est. primary completion date: April 2015
• 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 arisen at any extranodal site

2. any stage (Ann Arbor I-IV)

3. either de novo, or relapsed disease following local therapy (including surgery, radiotherapy and antibiotics for H. pylori-positive gastric lymphoma)

4. no evidence of histologic transformation to a high grade lymphoma

5. measurable or evaluable disease

6. age > 18

7. life expectancy of at least 1 year

8. ECOG performance status 0-2

9. no prior diagnosis of neoplasm within 5 years, except cervical intraepithelial neoplasia type 1 (CIN1) or localized non-melanomatous skin cancer

10. no prior chemotherapy

11. no prior immunotherapy with any anti-CD20 monoclonal antibody

12. no prior radiotherapy in the last 6 weeks

13. no 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

14. no 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

15. no evidence of symptomatic central nervous system (CNS) disease

16. no impairment of bone marrow function (WBC >3.0x109/L, ANC >1.5x109/L, PLT >100x109/L), unless due to lymphoma involvement

17. no major impairment of renal function (serum creatinine <1,5x upper normal) or liver function (ASAT/ALAT <2,5 upper normal, total bilirubin <2,5x upper normal), unless due to lymphoma involvement

18. no evidence of active opportunistic infections

19. no known HIV infection

20. no active HBV and/or HCV infection

21. no pregnant or lactating status

22. appropriate contraceptive method in women of childbearing potential or men

23. absence of 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

24. informed consent must be given according to national/local regulations before randomization

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, B-Cell, Marginal Zone
• Lymphoma, Mucosa-Associated Lymphoid Tissue

Intervention

Drug:
• chlorambucil (drug)
chlorambucil 6 mg/m2 daily during the first 6 weeks of treatment, two weeks rest, chlorambucil 6 mg/m2 daily during the first two of a four weeks cycles (total of 4 cycles)
• rituximab+chlorambucil
rituximab 375 mg/m2 iv, d1, 8, 15, 22, chlorambucil 6 mg/m2 os, daily during the first 6 weeks of treatment, ; two weeks rest; chlorambucil 6 mg/m2 os, daily during the first two of a four weeks cycles (total of 4 cycles) rituximab 375 mg/m2 iv at day 1 of each cycle
• rituximab
rituximab 375 mg/m2 iv on days 1, 8, 15, 22, 56, 84, 112, 140

Locations

Country	Name	City	State
Belgium	ACZA Campus Stuivenberg	Antwerpen
Belgium	AZ StJan	Brugge
Belgium	St Luc	Bruxelles
Belgium	ULB Hopital Erasme	Bruxelles
Belgium	CHNDRF	Charleroi
Belgium	Hospital St Joseph	Gilly
Belgium	UCL de Mont Godinne	Yvoir
France	Centre Hospitalier de Blois	Blois
France	Hopital Avicenne	Bobigny
France	CHU	Dijon
France	Centre Hospitalier	Lens
France	CHRU Lille	Lille
France	Centre Hospitalier Lyon Sud	Lyon
France	Centre Leon Berard	Lyon
France	Institut Paoli Calmettes	Marseille
France	Hopital Arnold Villeneuve	Monpellier
France	CHU	Nancy
France	CHU Hotel Dieu	Nantes
France	Centre R. Gauducheau	Nantes-St. Herblain
France	Hopital Henri-Mondor	Paris
France	Hopital St Louis	Paris
France	Necker	Paris
France	Centre Henri Becquerel	Rouen
Italy	Spedali Civili	Brescia
Italy	Azienda ULSS 15 Alta Padovana	Cittadella
Italy	IST	Genova
Italy	Humanitas	Milan
Italy	San Raffaele Hospital	Milan
Italy	IEO	Milano
Italy	INT	Milano
Italy	Policlinico	Modena
Italy	Ospedale Civile	Piacenza
Italy	A.O. Bianchi-Melacrino-Morelli, Divisione di Ematologia	Reggio Calabria
Italy	Arcispedale S. Maria Nuova	Reggio Emilia
Italy	S. Eugenio	Rome
Italy	Università Cattolica Sacro Cuore	Rome
Italy	Università La Sapienza	Rome
Italy	Sassuolo GISL	Sassuolo
Italy	AOU Senese	Siena
Italy	A.O.U. San Giovanni Battista-Molinette, S.C. Ematologia 2	Torino
Italy	Trani GISL	Trani
Italy	Ospedale di Circolo Fondazione Macchi	Varese
Italy	Policlinico GB Rossi	Verona
Spain	Clinic Hospital Universitari	Barcelona
Spain	Hopital Mataro'	Barcelona
Spain	Hopital Santa Creu i Sant Pau	Barcelona
Spain	University Hospital	Salamanca
Spain	Joan XXIII	Tarragona
Switzerland	IOSI	Bellinzona
United Kingdom	Aberdeen Royal Infirmary	Aberdeen
United Kingdom	Heartlands	Birmingham
United Kingdom	Victoria Hospital	Blackpool
United Kingdom	Royal Cornwall Hospital	Cornwall
United Kingdom	Darent Valley Hospital	Dartford
United Kingdom	Royal Devon &Exeter Healtcare NHS Trust	Devon
United Kingdom	Russels Hall Hospital	Dudley
United Kingdom	Western General Hospital	Edinburgh
United Kingdom	Medway Hospital	Gillingham
United Kingdom	Raigmore Hospital	Inverness
United Kingdom	Liverpool Royal Hospital	Liverpool
United Kingdom	University Hospital Aintree	Liverpool
United Kingdom	Barts & the London NHS Trust	London
United Kingdom	Royal Marsden NHS Foundation Trust	London
United Kingdom	St Georges	London
United Kingdom	Christie Hospital	Manchester
United Kingdom	Mount Vernon Hospital	Middlesex
United Kingdom	James Paget Hospital	Norfolk
United Kingdom	Queen Elisabeth	Norfolk
United Kingdom	Nottingham City Hospital	Nottingham
United Kingdom	John Radcliffe	Oxford
United Kingdom	Conquest Hospital	Saint Leonard On Sea
United Kingdom	Weston Park	Sheffield
United Kingdom	Southampton General Hospital	Southampton
United Kingdom	Sandwell General Hospital	West Bromwich
United Kingdom	Worchestershire Acute Hospital NHS Trust	Worcester

Sponsors (1)

Lead Sponsor	Collaborator
International Extranodal Lymphoma Study Group (IELSG)

Countries where clinical trial is conducted

Belgium,  France,  Italy,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event-free-survival (EFS)	Percentage of patients without events (failure of treatment or Death from any cause) after 5 years from trial registration	5 years
Secondary	Complete and Partial Remission Rate - Percentage of Patients With Complete and Partial Response at the End of Treatment	Response criteria were defined according to the NCI standardized response criteria for non-Hodgkin's lymphoma.; Complete response. Disappearance of all detectable clinical and radiographic evidence of disease, disappearance of all disease-related symptoms, if present before therapy, and normalization of those biochemical abnormalities definitely assignable to NHL. Regression of all lymph nodes and nodal masses to normal (= 1.5 cm in their greatest transverse diameter for nodes > 1.5 cm before therapy and to = 1 cm for nodes that were 1.1-1.5 cm. Regression by more than 75% in the sum of the products of the greatest diameters).; Partial response. Decrease by at least 50% in SPD of the six largest measurable lesions. It is not necessary for all lesions to have regressed to qualify for partial response, but no lesion should have progressed and no new lesion should appear.; For primary gastric sites, response was based on GELA histologic grading system.	End of treatment (after 24 weeks of therapy)
Secondary	Response Duration (Time to Relapse or Progression) - Percentage of Patients in Continuous Remission at Five Years From Trial Registration	Response criteria were defined according to the NCI standardized response criteria for non-Hodgkin's lymphoma.; Complete response (CR). Disappearance of all detectable clinical and radiographic evidence of disease, disappearance of all disease-related symptoms, if present before therapy, and normalization of those biochemical abnormalities definitely assignable to NHL. Regression of all lymph nodes and nodal masses to normal (= 1.5 cm in their greatest transverse diameter for nodes > 1.5 cm before therapy and to = 1 cm for nodes that were 1.1-1.5 cm. Regression by more than 75% in the sum of the products of the greatest diameters).	5 years
Secondary	Progression-free-survival (PFS)	Percentage of patients without disease progression after 5 years from trial registration	5 years
Secondary	Overall Survival	Percentage of patients alive after 5 years from trial registration	5 years

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