NCT01659099

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.

Trial Health

60
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
671

participants targeted

Target at P75+ for phase_3

Timeline
Completed

Started Sep 2012

Longer than P75 for phase_3

Geographic Reach
2 countries

122 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 4, 2012

Completed
1 month until next milestone

First Posted

Study publicly available on registry

August 7, 2012

Completed
25 days until next milestone

Study Start

First participant enrolled

September 1, 2012

Completed
3.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2016

Completed
1.4 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2017

Completed
Last Updated

March 7, 2018

Status Verified

March 1, 2018

Enrollment Period

3.9 years

First QC Date

July 4, 2012

Last Update Submit

March 6, 2018

Conditions

Keywords

DLBCLaa-IPI > or equal to 1Diagnosis18 to 60 yearsLymphoma

Outcome Measures

Primary Outcomes (1)

  • 2-year Event Free Survival

    EFS is defined as PET positivity according to ΔSUVmax criteria after 2 or 4 induction cycles as defined by RAC (based on central PET review), progression or relapse according to Cheson 2007, modification of planned treatment out of progression or death of any cause.

    Up to 2 years

Secondary Outcomes (9)

  • • Overall Response rate and Best overall response after 4 cycles and end of treatment according to Cheson 2007 criteria

    Up to 3.5years

  • • Overall Response Rate and Best overall response after 4 cycles and end of treatment according to Cheson 1999 criteria

    Up to 3.5 years

  • • Duration of response (DoR)

    Up to 6.5 years

  • • Progression-Free Survival (PFS)

    Up to 6.5 years

  • • Overall survival (OS)

    Up to 6.5 years

  • +4 more secondary outcomes

Study Arms (2)

GA101

EXPERIMENTAL

GA101 - Chemotherapy (ACVBP or CHOP)

Drug: GA101Drug: DoxorubicinDrug: CyclophosphamideDrug: PrednisoneDrug: BleomycinDrug: VindesinDrug: Vincristine

Rituximab

ACTIVE COMPARATOR

Rituximab - Chemotherapy (ACVBP or CHOP)

Drug: RituximabDrug: DoxorubicinDrug: CyclophosphamideDrug: PrednisoneDrug: BleomycinDrug: VindesinDrug: Vincristine

Interventions

GA101DRUG

in GA-ACBVP or in GA-CHOP 1000 mg on D1 and D8 (D8 in cycle 1 and 2)

Also known as: obinutuzumab, Gazivaro
GA101

in R-ACBVP or in R-CHOP 375 mg/m² on D1

Also known as: Mabthera
Rituximab

in ACBVP : 75 mg/m² on D1 in CHOP : 50 mg/m² on D1

GA101Rituximab

in ACBVP : 1200 mg/m² on D1 in CHOP : 750 mg/m² on D1

GA101Rituximab

in ACBVP : 60 mg/m² from D1 to D5 in CHOP : 40 mg/m² from D1 to D5

GA101Rituximab

in ACBVP 10 mg from D1 to D5

GA101Rituximab

in ACBVP 2 mg/m² from D1 to D5

GA101Rituximab

in CHOP 1,4 mg/m² on D1

GA101Rituximab

Eligibility Criteria

Age18 Years - 60 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • 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
  • 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

You may not qualify if:

  • 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)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (122)

ZNA Stuivenberg

Antwerp, 2060, Belgium

Location

Hôpital Saint Joseph

Arlon, 6700, Belgium

Location

RHMS Baudour

Baudour, 7331, Belgium

Location

AZ St Jan Brugge Oostende AV

Bruges, 8000, Belgium

Location

Institut Jules Bordet

Brussels, 1000, Belgium

Location

CHU Brugmann

Brussels, 1020, Belgium

Location

Hôpital Erasme

Brussels, 1070, Belgium

Location

Clinique universitaire Saint LUC

Brussels, 1200, Belgium

Location

CHU de Charleroi

Charleroi, 6000, Belgium

Location

Grand Hôpital de Charleroi

Charleroi, 6000, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, 900, Belgium

Location

Ch Jolimont

Haine-Saint-Paul, 7100, Belgium

Location

AZ GROENINGE - Oncology Centre - Campus Maria's Voorzienigheid

Kortrijk, 8500, Belgium

Location

CHR de la Citadelle

Liège, 4000, Belgium

Location

CHU de Liège - Clinique Saint Joseph

Liège, 4000, Belgium

Location

CHU de Liège -Domaine Sart Tilman

Liège, 4000, Belgium

Location

CHU Ambroise Paré

Mons, 7000, Belgium

Location

Clinique Saint Joseph -Hôpital de Warquignies

Mons, 7000, Belgium

Location

Clinique Sainte Elisabeth

Namur, 5000, Belgium

Location

Clinique Saint Pierre

Ottignies, 1340, Belgium

Location

Heilig Hart Ziekenhuis

Roeselare, 8800, Belgium

Location

Centre Hospitalier de Wallonie Picarde - CHwapi

Tournai, 7500, Belgium

Location

CH de la Tourelle-Peltzer

Verviers, 4800, Belgium

Location

Université Catholique de Louvain Mont Godinne

Yvoir, 5530, Belgium

Location

CH d'Abbeville

Abbeville, 80142, France

Location

CHU d'Amiens - Hôpital Sud

Amiens, 80054, France

Location

CHU d'Angers

Angers, 49033, France

Location

CH Victor Dupouy

Argenteuil, 95100, France

Location

CH d'Arras

Arras, 62022, France

Location

CH d'Avignon

Avignon, 84902, France

Location

Hôpital de Bayonne - CHU de la Côte Basque

Bayonne, 64109, France

Location

CH de Beauvais

Beauvais, 60000, France

Location

CHU de Besançon - Hôpital Jean Minjoz

Besançon, 25030, France

Location

CH de Blois

Blois, 41016, France

Location

APHP - Hôpital Avicenne

Bobigny, 93000, France

Location

Institut Bergonié

Bordeaux, 33076, France

Location

Polyclinique Bordeaux Nord Aquitaine

Bordeaux, 33077, France

Location

CH Dr Duchenne

Boulogne-sur-Mer, 62321, France

Location

CH Fleyriat

Bourg-en-Bresse, 01012, France

Location

CHU de Brest - Hôpital de Morvan

Brest, 29609, France

Location

CH Brive la Gaillarde

Brive-la-Gaillarde, 19100, France

Location

CHU de Caen

Caen, 14033, France

Location

Centre François Baclesse

Caen, 14076, France

Location

CH de Cannes

Cannes, 06400, France

Location

Clinique Du Parc

Castelnau-le-Lez, 34170, France

Location

CH de Chambéry

Chambéry, 73011, France

Location

CHU de Châlon sur Saône

Châlon Sur Saône, 71100, France

Location

APHP - Hôpital Antoine Béclère

Clamart, 92140, France

Location

Hôpital d'Instruction des Armées Percy

Clamart, 92141, France

Location

CHU d'Estaing

Clermont-Ferrand, 63003, France

Location

Pôle Santé Publique

Clermont-Ferrand, 63050, France

Location

CH de Compiègne

Compiègne, 60200, France

Location

CH Sud Francilien

Corbeil-Essonnes, 91100, France

Location

APHP - Hôpital Henri Mondor

Créteil, 94010, France

Location

CHU de Dijon

Dijon, 21000, France

Location

CH de Dunkerque

Dunkirk, 59385, France

Location

Institut Daniel Hollard

Grenoble, 38000, France

Location

CHU de Grenoble

Grenoble, 38043, France

Location

CHD Vendée

La Roche-sur-Yon, 85925, France

Location

CH La Rochelle

La Rochelle, 17019, France

Location

APHP - Hôpital Bicêtre

Le Kremlin-Bicêtre, 94275, France

Location

CH du Mans

Le Mans, 72000, France

Location

Clinique Victor Hugo

Le Mans, 72000, France

Location

CH de Lens

Lens, 62307, France

Location

CH Saint Vincent de Paul

Lille, 59000, France

Location

CHRU Lille - Hôpital Claude Huriez

Lille, 59037, France

Location

CHU Dupruytren - Limoges

Limoges, 87042, France

Location

CH Bretagne Sud

Lorient, 56100, France

Location

Centre Léon Bérard

Lyon, 69008, France

Location

CH Mantes La Jolie

Mantes-la-Jolie, 78201, France

Location

Hôpital de la Conception

Marseille, 13005, France

Location

Institut Paoli Calmettes

Marseille, 13009, France

Location

CH de Meaux

Meaux, 77100, France

Location

CH Marc Jacquet

Melun, 77011, France

Location

Hôpital Notre Dame Bon Secours

Metz, 57038, France

Location

CHI de Meulan

Meulan-en-Yvelines, 78250, France

Location

CHU de Montpellier - Saint Eloi

Montpellier, 34295, France

Location

Centre Val d'Aurélie - Paul Lamarque

Montpellier, 34298, France

Location

Centre Auréen de Cancérologie

Mougins, 06250, France

Location

CH de Mulhouse - Hôpital Emile Muller

Mulhouse, 68070, France

Location

CHU de Nantes - Hôtel Dieu

Nantes, 44093, France

Location

Centre Catherine de Sienne

Nantes, 44200, France

Location

Centre Antoine Lacassagne

Nice, 06189, France

Location

CHU de Nice

Nice, 06202, France

Location

CHU de Nîmes

Nîmes, 30029, France

Location

Clinique Valdegour

Nîmes, 30900, France

Location

CHR d'Orléans

Orléans, 45067, France

Location

Institut Curie

Paris, 75005, France

Location

APHP - Hôpital de la Pitié Salpetrière

Paris, 75013, France

Location

Hôpital Cochin

Paris, 75014, France

Location

APHP - Hôpital Necker

Paris, 75015, France

Location

APHP - Hôpital Saint Louis

Paris, 75475, France

Location

APHP - Hôpital Saint Antoine

Paris, 75571, France

Location

CH Saint Jean

Perpignan, 66000, France

Location

CHU de Haut Lévèque

Pessac, 33604, France

Location

Hospices Civils de Lyon - CHU Lyon Sud

Pierre-Bénite, 69495, France

Location

CHU de Poitiers

Poitiers, 86000, France

Location

CH René Dubos

Pontoise, 95300, France

Location

CH d'Annecy

Pringy, 74370, France

Location

CHU Robert Debré

Reims, 51100, France

Location

Institut du Cancer de Courlancy

Reims, 51100, France

Location

CHU de Rennes

Rennes, 35033, France

Location

CH de Roubaix

Roubaix, 59100, France

Location

Centre Henri Becquerel

Rouen, 76000, France

Location

Clinique Mathilde

Rouen, 76000, France

Location

CH Yves Le Foll - St Brieuc

Saint-Brieuc, 22000, France

Location

Centre René Huguenin

Saint-Cloud, 92210, France

Location

CHI de Poissy St Germain

Saint-Germain-en-Laye, 78105, France

Location

Institut de Cancérologie

Saint-Priest-en-Jarez, 42270, France

Location

CH de Saint Quentin

Saint-Quentin, 21000, France

Location

CHU de Saint Malo

St-Malo, 35400, France

Location

Strasbourg Oncologie Libérale

Strasbourg, 67000, France

Location

CHU de Strasbourg

Strasbourg, 67098, France

Location

Hopital Saint Husse

Toulon, 83100, France

Location

Institut Universitaire du Cancer - Oncopole Toulouse (IUCT-O)

Toulouse, 31059, France

Location

CHU de Tours

Tours, 37000, France

Location

CHU de Valence

Valence, 26953, France

Location

CH de Valenciennes

Valenciennes, 59322, France

Location

CHU de Brabois

Vandœuvre-lès-Nancy, 54511, France

Location

CH Bretagne Atlantique

Vannes, 56017, France

Location

CH de Versailles

Versailles, 78750, France

Location

Institut Gustave Roussy

Villejuif, 84085, France

Location

Related Publications (5)

  • Camus V, Molina T, Desmots F, Blanc-Durand P, Kanoun S, Moslemi A, Ruminy P, Le Gouill S, Ghesquieres H, Oberic L, Morschhauser F, Tilly H, Ribrag V, Houot R, Thieblemont C, Maisonneuve H, Claves F, Bouabdallah K, Haioun C, Damaj GL, Fornecker LM, Noel R, Feugier P, Sibon D, Cartron G, Bonnet C, Bernard W, Kraeber-Bodere F, Bodet-Milin C, Jais JP, Briere J, Rossi C, Elsensohn MH, Chartier L, Itti E, Jardin F, Fest T. Interim PET after 4 cycles predicts outcome in histomolecularly confirmed primary mediastinal B-cell lymphoma. Blood Adv. 2025 May 13;9(9):2232-2246. doi: 10.1182/bloodadvances.2024015577.

  • Itti E, Blanc-Durand P, Berriolo-Riedinger A, Kanoun S, Kraeber-Bodere F, Meignan M, Gat E, Gouill SL, Casasnovas RO, Bodet-Milin C. Validation of the DeltaSUVmax for Interim PET Interpretation in Diffuse Large B-Cell Lymphoma on the Basis of the GAINED Clinical Trial. J Nucl Med. 2023 Nov;64(11):1706-1711. doi: 10.2967/jnumed.123.265871. Epub 2023 Sep 21.

  • 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.

  • 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.

  • 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.

MeSH Terms

Conditions

DiseaseLymphoma

Interventions

obinutuzumabRituximabDoxorubicinCyclophosphamidePrednisoneBleomycinVindesineVincristine

Condition Hierarchy (Ancestors)

Pathologic ProcessesPathological Conditions, Signs and SymptomsNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-DerivedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsDaunorubicinAnthracyclinesNaphthacenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsPolycyclic CompoundsAminoglycosidesGlycosidesCarbohydratesPhosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedPhosphoramidesOrganophosphorus CompoundsPregnadienediolsPregnadienesPregnanesSteroidsFused-Ring CompoundsGlycopeptidesGlycoconjugatesPeptidesVinca AlkaloidsSecologanin Tryptamine AlkaloidsIndole AlkaloidsAlkaloidsHeterocyclic CompoundsIndolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingIndolizidinesIndolizines

Study Officials

  • Olivier Casasnovas, MD

    Lymphoma Study Association

    STUDY CHAIR
  • Steven Le Gouill, MD

    Lymphoma Study Association

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 4, 2012

First Posted

August 7, 2012

Study Start

September 1, 2012

Primary Completion

August 1, 2016

Study Completion

December 31, 2017

Last Updated

March 7, 2018

Record last verified: 2018-03

Locations