Clinical trial NCT01659099: GA In NEwly Diagnosed Diffuse Large B Cell Lymphoma
Official title: Randomized Phase III Study Using a Pet-driven Strategy and Comparing GA101 OR Rituximab Associated to a Chemotherapy Delivered Every 14 Days (ACVBP or CHOP) in DLBCL CD20+ Lymphoma Untreated Patients From 18 to 60 Presenting With 1 or More Adverse Prognostic Factors of the Age-adjusted IPI
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Diffuse Large B Cell Lymphoma CD20 Positive
Keywords: DLBCL
aa-IPI > or equal to 1
Diagnosis
18 to 60 years
Lymphoma
Lead sponsor: The Lymphoma Academic Research Organisation
Sponsor class: OTHER
Collaborators: name: Hoffmann-La Roche
First posted: 2012-08-07
Enrollment: 671
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is designed to investigate:

* the interest of a new monoclonal antibody (GA101)versus rituximab
* the interest of PET to identify early responders

Patients will receive either rituximab (standard treatment), either GA101 (study treatment), according to the randomization arm.

The monoclonal antibody will be associated to a chemotherapy: CHOP or ACVBP according to site's choice.A PET scan will be done before inclusion, after 2 chemotherapy cycles, and after 4 chemotherapy cycles, to identify early patients responders, for who consolidation with ASCT is not required.


Eligibility criteria: Inclusion Criteria:

* Histologically proven CD20+ diffuse large B cell lymphoma (WHO Classification)
* Baseline PET scan available with at least one hypermetabolic lesion
* Aged ≥ 18 years and ≤ 60 years
* Eligible for autologous stem cell transplant
* Patient not previously treated
* Age adjusted International Prognostic Index (aa-IPI) equal to 1, 2 or 3
* Life expectancy ≥ 3 months
* Negative HIV, HBV (anti-HBc negativity) and HCV serologies before inclusion
* Having signed a written informed consent
* Having ability and willingness to comply with study protocol procedures
* Men must agree to use a barrier method of contraception during the treatment period and until 3 months after the last dose of GA101 or rituximab, or ACVBP14 or CHOP14 chemotherapy, whichever is longer
* Women of childbearing potential must agree to use an adequate method of contraception, such as oral contraceptives, intrauterine device, or barrier method of contraception during the treatment period and until 12 months after the last dose of GA101, Rituximab, ACVBP14, or CHOP14 chemotherapy, whichever is longer

Exclusion Criteria:

* Any other histological type of lymphoma
* Any history of treated or non-treated indolent lymphoma. However, patients not previously diagnosed and having a diffuse large B-cell lymphoma with some small cell infiltration in bone marrow or lymph node may be included
* Central nervous system or meningeal involvement by lymphoma
* Contra-indication to any drug contained in the chemotherapy regimens
* Poor cardiac function (LVEF \< 50%) on echocardiogram or MUGA scan
* Poor renal function (creatinine level \> 150\*mol/l or clearance \< 30ml/min), poor hepatic function (total bilirubin level \> 30µmol/l, transaminases \> 2.5 X maximum normal level) unless these abnormalities are related to the lymphoma
* Poor bone marrow reserve as defined by neutrophils \< 1.5 G/L or platelets \< 100 G/L, unless related to bone marrow infiltration
* Any history of cancer during the last 5 years, with the exception of non-melanoma skin tumors or stage 0 (in situ) cervical carcinoma
* Any serious active disease (according to the investigator's decision)
* Treatment with any investigational drug within 30 days before planned first cycle of chemotherapy
* Pregnant or lactating women
* Adult patient under tutelage
* Prior history of Progressive Multifocal Leukoencephalopathy (PML)

Primary outcomes:
measure: 2-year Event Free Survival
timeFrame: Up to 2 years
Secondary outcomes:
measure: • Overall Response rate and Best overall response after 4 cycles and end of treatment according to Cheson 2007 criteria
timeFrame: Up to 3.5years
measure: • Overall Response Rate and Best overall response after 4 cycles and end of treatment according to Cheson 1999 criteria
timeFrame: Up to 3.5 years
measure: • Duration of response (DoR)
timeFrame: Up to 6.5 years
measure: • Progression-Free Survival (PFS)
timeFrame: Up to 6.5 years
measure: • Overall survival (OS)
timeFrame: Up to 6.5 years
measure: • Blood samples and on tumor tissue biopsy
timeFrame: Up to 6.5 years
measure: • Focus on subpopulation
timeFrame: Up to 6.5 years
measure: Number of stem cell collected after GA101 treatment
timeFrame: Up to 3.5 years
measure: • Early metabolic response according to PET after 2 and 4 cycles
timeFrame: Up to 3.5 years
Other outcomes:
Locations:
city: Antwerpen
country: Belgium
facility: ZNA Stuivenberg
city: Arlon
country: Belgium
facility: Hôpital Saint Joseph
city: Baudour
country: Belgium
facility: RHMS Baudour
city: Brugge
country: Belgium
facility: AZ St Jan Brugge Oostende AV
city: Bruxelles
country: Belgium
facility: Institut Jules Bordet
city: Bruxelles
country: Belgium
facility: CHU Brugmann
city: Bruxelles
country: Belgium
facility: Hôpital Erasme
city: Bruxelles
country: Belgium
facility: Clinique universitaire Saint LUC
city: Charleroi
country: Belgium
facility: CHU de Charleroi
city: Charleroi
country: Belgium
facility: Grand Hôpital de Charleroi
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Haine Saint Paul
country: Belgium
facility: Ch Jolimont
city: Kortrijk
country: Belgium
facility: AZ GROENINGE - Oncology Centre - Campus Maria's Voorzienigheid
city: Liège
country: Belgium
facility: CHR de la Citadelle
city: Liège
country: Belgium
facility: CHU de Liège - Clinique Saint Joseph
city: Liège
country: Belgium
facility: CHU de Liège -Domaine Sart Tilman
city: Mons
country: Belgium
facility: CHU Ambroise Paré
city: Mons
country: Belgium
facility: Clinique Saint Joseph -Hôpital de Warquignies
city: Namur
country: Belgium
facility: Clinique Sainte Elisabeth
city: Ottignies
country: Belgium
facility: Clinique Saint Pierre
city: Roeselare
country: Belgium
facility: Heilig Hart Ziekenhuis
city: Tournai
country: Belgium
facility: Centre Hospitalier de Wallonie Picarde - CHwapi
city: Verviers
country: Belgium
facility: CH de la Tourelle-Peltzer
city: Yvoir
country: Belgium
facility: Université Catholique de Louvain Mont Godinne
city: Abbeville
country: France
facility: CH d'Abbeville
city: Amiens
country: France
facility: CHU d'Amiens - Hôpital Sud
city: Angers
country: France
facility: CHU d'Angers
city: Argenteuil
country: France
facility: CH Victor Dupouy
city: Arras
country: France
facility: CH d'Arras
city: Avignon
country: France
facility: CH d'Avignon
city: Bayonne
country: France
facility: Hôpital de Bayonne - CHU de la Côte Basque
city: Beauvais
country: France
facility: CH de Beauvais
city: Besançon
country: France
facility: CHU de Besançon - Hôpital Jean Minjoz
city: Blois
country: France
facility: CH de Blois
city: Bobigny
country: France
facility: APHP - Hôpital Avicenne
city: Bordeaux
country: France
facility: Institut Bergonié
city: Bordeaux
country: France
facility: Polyclinique Bordeaux Nord Aquitaine
city: Boulogne sur Mer
country: France
facility: CH Dr Duchenne
city: Bourg en Bresse
country: France
facility: CH Fleyriat
city: Brest
country: France
facility: CHU de Brest - Hôpital de Morvan
city: Brive la Gaillarde
country: France
facility: CH Brive la Gaillarde
city: Caen
country: France
facility: CHU de Caen
city: Caen
country: France
facility: Centre François Baclesse
city: Cannes
country: France
facility: CH de Cannes
city: Castelnau Le Lez
country: France
facility: Clinique Du Parc
city: Chambéry
country: France
facility: CH de Chambéry
city: Châlon sur Saône
country: France
facility: CHU de Châlon sur Saône
city: Clamart
country: France
facility: APHP - Hôpital Antoine Béclère
city: Clamart
country: France
facility: Hôpital d'Instruction des Armées Percy
city: Clermont Ferrand
country: France
facility: CHU d'Estaing
city: Clermont Ferrand
country: France
facility: Pôle Santé Publique
city: Compiègne
country: France
facility: CH de Compiègne
city: Corbeil Essonnes
country: France
facility: CH Sud Francilien
city: Créteil
country: France
facility: APHP - Hôpital Henri Mondor
city: Dijon
country: France
facility: CHU de Dijon
city: Dunkerque
country: France
facility: CH de Dunkerque
city: Grenoble
country: France
facility: Institut Daniel Hollard
city: Grenoble
country: France
facility: CHU de Grenoble
city: La Roche Sur Yon
country: France
facility: CHD Vendée
city: La Rochelle
country: France
facility: CH La Rochelle
city: Le Kremlin Bicêtre
country: France
facility: APHP - Hôpital Bicêtre
city: Le Mans
country: France
facility: CH du Mans
city: Le Mans
country: France
facility: Clinique Victor Hugo
city: Lens
country: France
facility: CH de Lens
city: Lille
country: France
facility: CH Saint Vincent de Paul
city: Lille
country: France
facility: CHRU Lille - Hôpital Claude Huriez
city: Limoges
country: France
facility: CHU Dupruytren - Limoges
city: Lorient
country: France
facility: CH Bretagne Sud
city: Lyon
country: France
facility: Centre Léon Bérard
city: Mantes La Jolie
country: France
facility: CH Mantes La Jolie
city: Marseille
country: France
facility: Hôpital de la Conception
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Meaux
country: France
facility: CH de Meaux
city: Melun
country: France
facility: CH Marc Jacquet
city: Metz
country: France
facility: Hôpital Notre Dame Bon Secours
city: Meulan en Yvelines
country: France
facility: CHI de Meulan
city: Montpellier
country: France
facility: CHU de Montpellier - Saint Eloi
city: Montpellier
country: France
facility: Centre Val d'Aurélie - Paul Lamarque
city: Mougins
country: France
facility: Centre Auréen de Cancérologie
city: Mulhouse Cedex
country: France
facility: CH de Mulhouse - Hôpital Emile Muller
city: Nantes
country: France
facility: CHU de Nantes - Hôtel Dieu
city: Nantes
country: France
facility: Centre Catherine de Sienne
city: Nice Cedex 2
country: France
facility: Centre Antoine Lacassagne
city: Nice
country: France
facility: CHU de Nice
city: Nîmes
country: France
facility: CHU de Nîmes
city: Nîmes
country: France
facility: Clinique Valdegour
city: Orléans
country: France
facility: CHR d'Orléans
city: Paris Cedex 10
country: France
facility: APHP - Hôpital Saint Louis
city: Paris Cedex 12
country: France
facility: APHP - Hôpital Saint Antoine
city: Paris
country: France
facility: Institut Curie
city: Paris
country: France
facility: APHP - Hôpital de la Pitié Salpetrière
city: Paris
country: France
facility: Hôpital Cochin
city: Paris
country: France
facility: APHP - Hôpital Necker
city: Perpignan
country: France
facility: CH Saint Jean
city: Pessac
country: France
facility: CHU de Haut Lévèque
city: Pierre Bénite
country: France
facility: Hospices Civils de Lyon - CHU Lyon Sud
city: Poitiers
country: France
facility: CHU de Poitiers
city: Pontoise
country: France
facility: CH René Dubos
city: Pringy
country: France
facility: CH d'Annecy
city: Reims
country: France
facility: CHU Robert Debré
city: Reims
country: France
facility: Institut du Cancer de Courlancy
city: Rennes
country: France
facility: CHU de Rennes
city: Roubaix
country: France
facility: CH de Roubaix
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Rouen
country: France
facility: Clinique Mathilde
city: Saint Brieuc
country: France
facility: CH Yves Le Foll - St Brieuc
city: Saint Cloud
country: France
facility: Centre René Huguenin
city: Saint germain en laye
country: France
facility: CHI de Poissy St Germain
city: Saint Malo
country: France
facility: CHU de Saint Malo
city: Saint Quentin
country: France
facility: CH de Saint Quentin
city: St Priest en Jarez
country: France
facility: Institut de Cancérologie
city: Strasbourg
country: France
facility: Strasbourg Oncologie Libérale
city: Strasbourg
country: France
facility: CHU de Strasbourg
city: Toulon
country: France
facility: Hopital Saint Husse
city: Toulouse
country: France
facility: Institut Universitaire du Cancer - Oncopole Toulouse (IUCT-O)
city: Tours
country: France
facility: CHU de Tours
city: Valence
country: France
facility: CHU de Valence
city: Valenciennes
country: France
facility: CH de Valenciennes
city: Vandœuvre-lès-Nancy
country: France
facility: CHU de Brabois
city: Vannes
country: France
facility: CH Bretagne Atlantique
city: Versailles
country: France
facility: CH de Versailles
city: Villejuif
country: France
facility: Institut Gustave Roussy
Study officials:
affiliation: Lymphoma Study Association
name: Olivier Casasnovas, MD
role: STUDY_CHAIR
affiliation: Lymphoma Study Association
name: Steven Le Gouill, MD
role: STUDY_CHAIR
References:
citation: Jullien M, Tessoulin B, Ghesquieres H, Oberic L, Morschhauser F, Tilly H, Ribrag V, Lamy T, Thieblemont C, Villemagne B, Gressin R, Bouabdallah K, Haioun C, Damaj G, Fornecker LM, Schiano De Colella JM, Feugier P, Hermine O, Cartron G, Bonnet C, Andre M, Bailly C, Casasnovas RO, Le Gouill S. Deep-Learning Assessed Muscular Hypodensity Independently Predicts Mortality in DLBCL Patients Younger Than 60 Years. Cancers (Basel). 2021 Sep 7;13(18):4503. doi: 10.3390/cancers13184503.
citation: Le Gouill S, Ghesquieres H, Oberic L, Morschhauser F, Tilly H, Ribrag V, Lamy T, Thieblemont C, Maisonneuve H, Gressin R, Bouhabdallah K, Haioun C, Damaj G, Fornecker L, Bouhabdallah R, Feugier P, Sibon D, Cartron G, Bonnet C, Andre M, Chartier L, Ruminy P, Kraeber-Bodere F, Bodet-Milin C, Berriolo-Riedinger A, Briere J, Jais JP, Molina TJ, Itti E, Casasnovas RO. Obinutuzumab vs rituximab for advanced DLBCL: a PET-guided and randomized phase 3 study by LYSA. Blood. 2021 Apr 29;137(17):2307-2320. doi: 10.1182/blood.2020008750.
citation: Blanc-Durand P, Jegou S, Kanoun S, Berriolo-Riedinger A, Bodet-Milin C, Kraeber-Bodere F, Carlier T, Le Gouill S, Casasnovas RO, Meignan M, Itti E. Fully automatic segmentation of diffuse large B cell lymphoma lesions on 3D FDG-PET/CT for total metabolic tumour volume prediction using a convolutional neural network. Eur J Nucl Med Mol Imaging. 2021 May;48(5):1362-1370. doi: 10.1007/s00259-020-05080-7. Epub 2020 Oct 24.