Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Ended
Participants planned
112
Countries
2
Sites
38
Extranodal Marginal Zone Lymphoma
Aim of the study is to assess the therapeutic safety and activity of the combination of Chlorambucil and Rituximab given for 6 months, followed by 2 years maintenance treatment with subcutaneous Rituximab alone in MALT lymphomas.
Key facts
- Sponsor
- Association International Extranodal Lymphoma Study Group (IELSG)
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Neoplasms [C04]
- Trial duration
- 24 Mar 2014 → 27 May 2026
- Decision date (initial)
- 2024-10-01
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- Yes
- Vulnerable population
- Yes
- Funding sources
- Roche S.p.a.
External identifiers
- EU CT number
- 2023-507291-52-00
- EudraCT number
- 2012-004896-38
- ClinicalTrials.gov
- NCT01808599
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy, Efficacy, Safety
Aim of the study is to assess the therapeutic safety and activity of the combination of Chlorambucil and Rituximab given for 6 months, followed by 2 years maintenance treatment with subcutaneous Rituximab alone in MALT lymphomas.
Secondary objectives 1
- Efficacy and safety of study treatment
Conditions and MedDRA coding
Extranodal Marginal Zone Lymphoma
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 21.0 | PT | 10061850 | Extranodal marginal zone B-cell lymphoma (MALT type) | 100000004864 |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 4
- 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
- Measurable or evaluable disease
- Any stage (Ann Arbor I-IV)
- Age >= 18
Exclusion criteria 5
- Evidence of histologic transformation to a high grade lymphoma
- Prior chemotherapy
- Prior radiotherapy in the last 6 weeks
- Prior immunotherapy with any anti-CD20 monoclonal antibody
- Known HIV, active Hepatitis B (HB) and Hepatitis C (HC) infections
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Complete Remission rate at the end of induction phase (6 months)
Secondary endpoints 6
- Response Rate (Complete and partial remission rates) at the end of induction phase ( 6 months from study entry)
- Progression Free Survival
- Event-free-survival (EFS) at 5 years
- Overall survival
- Response duration
- Acute and long-term toxicity
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 3
MabThera 1400 mg solution for subcutaneous injection
PRD1182393 · Product
- Active substance
- Rituximab
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS
- Max daily dose
- 1400 mg milligram(s)
- Max total dose
- 1400 mg milligram(s)
- Max treatment duration
- 28 Month(s)
- Authorisation status
- Authorised
- ATC code
- L01XC02 — RITUXIMAB
- Marketing authorisation
- EU/1/98/067/003
- MA holder
- ROCHE REGISTRATION GMBH
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Labelling
MabThera 500 mg concentrate for solution for infusion
PRD398759 · Product
- Active substance
- Rituximab
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 375 mg/m2 milligram(s)/square meter
- Max total dose
- 375 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 6 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01XC02 — RITUXIMAB
- Marketing authorisation
- EU/1/98/067/002
- MA holder
- ROCHE REGISTRATION GMBH
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Labelling
SUB06172MIG · Substance
- Active substance
- Chlorambucil
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 6 mg/m2 milligram(s)/sq. meter
- Max total dose
- 6 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 6 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Association International Extranodal Lymphoma Study Group (IELSG)
- Sponsor organisation
- Association International Extranodal Lymphoma Study Group (IELSG)
- Address
- Via Vincenzo Vela 6
- City
- Bellinzona
- Postcode
- 6500
- Country
- Switzerland
Scientific contact point
- Organisation
- Association International Extranodal Lymphoma Study Group (IELSG)
- Contact name
- IELSG Operations Office
Public contact point
- Organisation
- Association International Extranodal Lymphoma Study Group (IELSG)
- Contact name
- IELSG Operations Office
Third parties 1
| Organisation | City, country | Duties |
|---|---|---|
| LYSARC ORG-100010583
|
Pierre Benite Cedex, France | On site monitoring, Code 12, Code 2 |
Locations
2 EU/EEA countries · 38 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| France | Ended | 40 | 14 |
| Italy | Ended | 66 | 24 |
| Rest of world
Switzerland
|
— | 6 | — |
Investigational sites
Centre Hospitalier Lyon Sud
Hematology, 165 Chemin Du Grand Revoyet, 69310, Pierre-Benite
Centre Hospitalier Regional Universitaire De Tours
Hematology, 2 Boulevard Tonnelle, 37000, Tours
Centre Hospitalier Universitaire De Dijon
Hematology, 10 10 boulevard de Tassigny, 21000, Dijon
Centre Hospitalier Universitaire De Montpellier
Hematology, 80 Avenue Augustin Fliche, 34295, Montpellier Cedex 5
Centre Henri Becquerel
Hematology, Rue D Amiens, 76038, Rouen Cedex
Assistance Publique Hopitaux De Paris
Hematology, 1 Avenue Claude Vellefaux, 75010, Paris
Centre Hospitalier Universitaire De Lille
Hematology, Rue Michel Polonovski, 59037, Lille Cedex
Assistance Publique Hopitaux De Paris
Hematology, 51 Avenue Du Mal De Lattre De Tassigny, 94010, Creteil Cedex
Centre Hospitalier Universitaire Grenoble Alpes
Hematology, Boulevard De La Chantourne, Cs 10217, Grenoble Cedex 9
Centre Hospitalier Universitaire De Rennes
Hematology, 2 Rue Henri Le Guilloux, 35000, Rennes
CHRU De Nancy
Hematology, Rue Du Morvan, 54500, Vandoeuvre Les Nancy
Centre Hospitalier Universitaire De Nantes
Hematology, 1 Place Alexis Ricordeau, 44000, Nantes
University Hospital Of Clermont-Ferrand
Hematology, 1 Place Lucie Et Raymond Aubrac, 63100, Clermont-Ferrand
Institut Paoli-Calmettes
Hematology, 232 Boulevard De Sainte Marguerite, Bp 156, Marseille
I.F.O. Istituti Fisioterapici Ospitalieri
Ematologia e Trapianto, Via Elio Chianesi N 53, 00144, Rome
Azienda Sanitaria Locale Della Provincia Di Biella
SSD Ematologia, Via Dei Ponderanesi 2, 13875, Ponderano
Azienda Ospedaliero-Universitaria Ss.Antonio E Biagio E C.Arrigo Alessandria
SCDU Ematologia, Via Venezia 16, 15121, Alexandria
Fondazione IRCCS Istituto Nazionale Dei Tumori
Ematologia, Via Giacomo Venezian 1, 20133, Milan
Azienda Unita' Sanitaria Locale Toscana Sud Est
U.O. Ematologia - Ospedale San Donato - USL8 - Arezzo, Ospedale Area Aretina Nord, Via Pietro Nenni 20/22, Arezzo
Azienda USL IRCCS Di Reggio Emilia
Ematologia, Viale Risorgimento 80, 42123, Reggio Emilia
Azienda Ospedaliera S Maria Di Terni
S.C. Oncoematologia, Viale Tristano Di Joannuccio 1, 05100, Terni
Azienda Ospedaliera Universitaria Citta Della Salute E Della Scienza Di Torino
S.C.Ematologia, Corso Bramante 88, 10126, Turin
Azienda Ospedaliero Universitaria Parma
UOC Ematologia e CTMO, Viale Antonio Gramsci 14, 43126, Parma
ARNAS G. Brotzu
SC Ematologia e CTMO - Ospedale Businco, Piazzale Alessandro Ricchi 1, 09121, Cagliari
Azienda Socio Sanitaria Territoriale Dei Sette Laghi
U.O.C Ematologia, Viale Luigi Borri N 57, 21100, Varese
Azienda Sanitaria Locale Di Salerno
U.O. Onco-ematologia - Presidio ospedaliero "A. TORTORA", Via Nizza 146, 84124, Salerno
Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.
Ematologia, Via Piero Maroncelli 40, 47014, Meldola
Azienda Unita Sanitaria Locale Della Romagna
Ematologia - Ospedale delle Croci, Viale Vincenzo Randi 5, 48121, Ravenna
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
Ematologia, Via Francesco Sforza 28, 20122, Milan
Azienda Unita' Sanitaria Locale Toscana Nord Ovest
Ematologia - Ospedale di Livorno, Via Antonio Cocchi 7/9, 56121, Pisa
Istituto Oncologico Veneto
Oncologia 1, Via Gattamelata 64, 35128, Padova
Azienda Ospedaliero Universitaria Delle Marche
Clinica di Ematologia - AOU Ospedali Riuniti, Via Conca 71, 60126, Ancona
Azienda Ospedaliera Universitaria Citta Della Salute E Della Scienza Di Torino
Ematologia Universitaria, Corso Bramante 88, 10126, Turin
Centro Di Riferimento Oncologico Di Aviano
Divisione di Oncologia e dei Tumori immuno-correlati, Via Franco Gallini 2, 33081, Aviano
Azienda Ospedaliero-Universitaria Policlinico Umberto I
Istituto Ematologia -Dipartimento di Medicina Traslazionale e di Precisione, Viale Del Policlinico 155, 00161, Rome
Azienda Unita Sanitaria Locale Della Romagna
U.O. di Ematologia -Ospedale degli Infermi di Rimini, Viale Luigi Settembrini 2, 47923, Rimini
Istituto Di Ricovero E Cura A Carattere Scientifico Centro Di Riferimento Oncologico Della Basilicata
UO di ematologia e Trapianto Cellule Staminali, Via Padre Pio 1, 85028, Rionero In Vulture
Azienda Sanitaria Locale Di Pescara
UOC Ematologia Dipartimento Oncologico Ematologico - ASL Pescara - P.O. Spirito Santo di Pescara, Via Renato Paolini 47, 65124, Pescara
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| France | 2014-04-06 | 2025-11-24 | 2014-05-19 | 2015-10-01 | |
| Italy | 2014-03-24 | 2026-05-27 | 2014-03-27 | 2016-03-01 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 20 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_IELSG38_Protocol_2023-507291-52-00_Redacted | 1.5 |
| Protocol (for publication) | D1_IELSG38_Protocol_2023-507291-52-00_TC | 1.5 |
| Recruitment arrangements (for publication) | K1_IELSG38_informed consent_patient recruitment arrangements | 1 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements redacted | 1 |
| Subject information and informed consent form (for publication) | L1_IELSG38 Addendum GDPR IT | 1.0 |
| Subject information and informed consent form (for publication) | L1_IELSG38 Privacy Information and consent form | 2.0 |
| Subject information and informed consent form (for publication) | L1_IELSG38_Letter to General Practitioner | 1.0 |
| Subject information and informed consent form (for publication) | L1_IELSG38_Patient Consent Form | 1.1 |
| Subject information and informed consent form (for publication) | L1_IELSG38_Patient Information Sheet_redacted | 1.2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Biologic samples redacted | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF study redacted | 1.1 |
| Subject information and informed consent form (for publication) | L2_IELSG38_Patient Diary Clorambucile part A | 2.0 |
| Subject information and informed consent form (for publication) | L2_IELSG38_Patient Diary Clorambucile part B | 2.0 |
| Subject information and informed consent form (for publication) | L2_Other subject information material_ Patient diary Phase 1 redacted | 1 |
| Subject information and informed consent form (for publication) | L2_Other subject information material_complementary information redacted | 1 |
| Subject information and informed consent form (for publication) | L2_Other subject information material_Patient diary Phase II redacted | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Leukeran_Chlorambucil_HPRA | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_mabthera_rituximab | NA |
| Synopsis of the protocol (for publication) | D1_IELSG38_Synopsis FR_2023-507291-52-00 | 1.4 |
| Synopsis of the protocol (for publication) | D1_IELSG38_Synpsis_IT_2023-507291-52-00 | 1 |
Application history
5 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-08-09 | Italy | Acceptable 2024-09-17
|
2024-10-01 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2024-10-31 | Acceptable | 2024-12-02 | |
| 3 | SUBSTANTIAL MODIFICATION | SM-2 | 2025-01-09 | Italy | Acceptable 2025-03-17
|
2025-03-18 |
| 4 | SUBSTANTIAL MODIFICATION | SM-3 | 2025-05-06 | Italy | Acceptable 2025-07-28
|
2025-07-31 |
| 5 | SUBSTANTIAL MODIFICATION | SM-4 | 2025-09-11 | Italy | Acceptable | 2025-11-25 |