GA In NEwly Diagnosed Diffuse Large B Cell Lymphoma
- Conditions
- Diffuse Large B Cell Lymphoma CD20 Positive
- Interventions
- Registration Number
- NCT01659099
- Lead Sponsor
- The Lymphoma Academic Research Organisation
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 671
- 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
- 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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description GA101 Doxorubicin GA101 - Chemotherapy (ACVBP or CHOP) GA101 Cyclophosphamide GA101 - Chemotherapy (ACVBP or CHOP) GA101 Vincristine GA101 - Chemotherapy (ACVBP or CHOP) GA101 Vindesin GA101 - Chemotherapy (ACVBP or CHOP) Rituximab Rituximab Rituximab - Chemotherapy (ACVBP or CHOP) Rituximab Vindesin Rituximab - Chemotherapy (ACVBP or CHOP) GA101 GA101 GA101 - Chemotherapy (ACVBP or CHOP) Rituximab Bleomycin Rituximab - Chemotherapy (ACVBP or CHOP) GA101 Bleomycin GA101 - Chemotherapy (ACVBP or CHOP) GA101 Prednisone GA101 - Chemotherapy (ACVBP or CHOP) Rituximab Prednisone Rituximab - Chemotherapy (ACVBP or CHOP) Rituximab Cyclophosphamide Rituximab - Chemotherapy (ACVBP or CHOP) Rituximab Doxorubicin Rituximab - Chemotherapy (ACVBP or CHOP) Rituximab Vincristine Rituximab - Chemotherapy (ACVBP or CHOP)
- Primary Outcome Measures
Name Time Method 2-year Event Free Survival Up to 2 years 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.
- Secondary Outcome Measures
Name Time Method • Overall survival (OS) Up to 6.5 years Overall survival is defined as the period from the date of randomization to the date of death from any cause. Alive patients at the time of the analysis will be censored at their last contact date
Number of stem cell collected after GA101 treatment Up to 3.5 years Number of stem cell collected after GA101 administration Number of required collects to achieve 3Mcells/kg.
• Progression-Free Survival (PFS) Up to 6.5 years Progression-Free Survival is defined as the period from the date of randomization to the date of first documented disease progression, relapse, or death from any cause. For patients who have not progressed, relapsed, or died at the time of analysis, PFS will be censored on the date of last disease assessment. If no tumor assessments were performed after the baseline visit, PFS will be censored at the time of randomization
• Blood samples and on tumor tissue biopsy Up to 6.5 years Analysis on blood samples and tumor tissue biopsy will be driven, in order to explore prognosis factors of the patients and their tumors that influence treatment response based on PET assessment and prognosis
• Overall Response Rate and Best overall response after 4 cycles and end of treatment according to Cheson 1999 criteria Up to 3.5 years Response will be assessed after 4 cycles and at the end of treatment, based on investigator assessment. Assessment of response will be based on the International Workshop to Standardize Response criteria for NHL Criteria for evaluation of response in Non-Hodgkin's lymphoma (Cheson, 1999). Overall (CR/CRu/PR) response rates and Best Overall Response Rate will be presented. Patient without response assessment (due to whatever reason) will be considered as non-responder.
• Duration of response (DoR) Up to 6.5 years Duration of response is defined as the period from the time of attainment a CR or PR to the date of progression, relapse or death from any cause. Duration or response would be assessed as survival in the whole population, in the two inductive arms (R-Chemo14 vs GA101-Chemo14) For patients achieving a response but who have not progressed or relapsed or died at the time of analysis, DOR will be censored on the date of last disease assessment
• Early metabolic response according to PET after 2 and 4 cycles Up to 3.5 years Based on results of central PET review
• Focus on subpopulation Up to 6.5 years Duration of response, PFS and OS will be performed according to treatment arms (R-Chemo14 vs GA101-Chemo14) on different analysis populations. The subpopulations are based on the outcome during the induction phase and a statistical bias could be introduced as subpopulations have not been defined at baseline.
* Population with a Δ SUVmaxPET0-2≤66% (slow and intermediate responders),
* Population with a Δ SUVmaxPET0-2\>66% (fast responders),
* Patients submitted to autologous stem cell transplant (PFS and OS only)• Overall Response rate and Best overall response after 4 cycles and end of treatment according to Cheson 2007 criteria Up to 3.5years Response will be assessed after 4 cycles and again at the end of treatment, based on RAC assessment for PET 4 and investigator assessment for EoT PET. Assessment of response will be based on the International Workshop to Standardize Response criteria for NHL Criteria for evaluation of response in Non-Hodgkin's lymphoma (Cheson, 2007). Overall (CR//PR) response rates and Best Response Rate will be presented. Patient without response assessment (due to whatever reason) will be considered as non-responder.
Trial Locations
- Locations (122)
Clinique universitaire Saint LUC
🇧🇪Bruxelles, Belgium
CHU Ambroise Paré
🇧🇪Mons, Belgium
Clinique Sainte Elisabeth
🇧🇪Namur, Belgium
Heilig Hart Ziekenhuis
🇧🇪Roeselare, Belgium
ZNA Stuivenberg
🇧🇪Antwerpen, Belgium
CHU Brugmann
🇧🇪Bruxelles, Belgium
Hôpital Saint Joseph
🇧🇪Arlon, Belgium
CHU de Charleroi
🇧🇪Charleroi, Belgium
Institut Jules Bordet
🇧🇪Bruxelles, Belgium
Grand Hôpital de Charleroi
🇧🇪Charleroi, Belgium
Hôpital Erasme
🇧🇪Bruxelles, Belgium
Universitair Ziekenhuis Gent
🇧🇪Gent, Belgium
Ch Jolimont
🇧🇪Haine Saint Paul, Belgium
CHR de la Citadelle
🇧🇪Liège, Belgium
Clinique Saint Pierre
🇧🇪Ottignies, Belgium
Centre Hospitalier de Wallonie Picarde - CHwapi
🇧🇪Tournai, Belgium
AZ GROENINGE - Oncology Centre - Campus Maria's Voorzienigheid
🇧🇪Kortrijk, Belgium
CHU de Liège -Domaine Sart Tilman
🇧🇪Liège, Belgium
Université Catholique de Louvain Mont Godinne
🇧🇪Yvoir, Belgium
Clinique Victor Hugo
🇫🇷Le Mans, France
CHU de Rennes
🇫🇷Rennes, France
CH de Roubaix
🇫🇷Roubaix, France
CH Brive la Gaillarde
🇫🇷Brive la Gaillarde, France
CH de Cannes
🇫🇷Cannes, France
CH de Chambéry
🇫🇷Chambéry, France
Hôpital d'Instruction des Armées Percy
🇫🇷Clamart, France
CH de Compiègne
🇫🇷Compiègne, France
CHD Vendée
🇫🇷La Roche Sur Yon, France
RHMS Baudour
🇧🇪Baudour, Belgium
CH de la Tourelle-Peltzer
🇧🇪Verviers, Belgium
CH de Beauvais
🇫🇷Beauvais, France
Institut Bergonié
🇫🇷Bordeaux, France
CH Fleyriat
🇫🇷Bourg en Bresse, France
CHU de Dijon
🇫🇷Dijon, France
CH de Dunkerque
🇫🇷Dunkerque, France
CHU de Grenoble
🇫🇷Grenoble, France
CH d'Abbeville
🇫🇷Abbeville, France
CH de Blois
🇫🇷Blois, France
Polyclinique Bordeaux Nord Aquitaine
🇫🇷Bordeaux, France
CH Dr Duchenne
🇫🇷Boulogne sur Mer, France
Clinique Du Parc
🇫🇷Castelnau Le Lez, France
CH Sud Francilien
🇫🇷Corbeil Essonnes, France
CH de Lens
🇫🇷Lens, France
CH Saint Vincent de Paul
🇫🇷Lille, France
CH Bretagne Sud
🇫🇷Lorient, France
CHU de Liège - Clinique Saint Joseph
🇧🇪Liège, Belgium
Clinique Saint Joseph -Hôpital de Warquignies
🇧🇪Mons, Belgium
CHU d'Amiens - Hôpital Sud
🇫🇷Amiens, France
CHU d'Angers
🇫🇷Angers, France
Hôpital de Bayonne - CHU de la Côte Basque
🇫🇷Bayonne, France
CHU de Besançon - Hôpital Jean Minjoz
🇫🇷Besançon, France
APHP - Hôpital Avicenne
🇫🇷Bobigny, France
CHU de Caen
🇫🇷Caen, France
CH Victor Dupouy
🇫🇷Argenteuil, France
CH d'Arras
🇫🇷Arras, France
APHP - Hôpital Saint Antoine
🇫🇷Paris Cedex 12, France
CH d'Avignon
🇫🇷Avignon, France
CHU de Brest - Hôpital de Morvan
🇫🇷Brest, France
Centre François Baclesse
🇫🇷Caen, France
APHP - Hôpital Antoine Béclère
🇫🇷Clamart, France
APHP - Hôpital Bicêtre
🇫🇷Le Kremlin Bicêtre, France
CHR d'Orléans
🇫🇷Orléans, France
CHU de Poitiers
🇫🇷Poitiers, France
APHP - Hôpital Saint Louis
🇫🇷Paris Cedex 10, France
CHI de Poissy St Germain
🇫🇷Saint germain en laye, France
CHU de Saint Malo
🇫🇷Saint Malo, France
Hopital Saint Husse
🇫🇷Toulon, France
CH de Valenciennes
🇫🇷Valenciennes, France
CH Bretagne Atlantique
🇫🇷Vannes, France
CH de Versailles
🇫🇷Versailles, France
CHU de Strasbourg
🇫🇷Strasbourg, France
CHU de Tours
🇫🇷Tours, France
CHU de Valence
🇫🇷Valence, France
CHU de Châlon sur Saône
🇫🇷Châlon sur Saône, France
APHP - Hôpital Henri Mondor
🇫🇷Créteil, France
Institut Daniel Hollard
🇫🇷Grenoble, France
CH La Rochelle
🇫🇷La Rochelle, France
CH du Mans
🇫🇷Le Mans, France
CHU de Montpellier - Saint Eloi
🇫🇷Montpellier, France
Centre René Huguenin
🇫🇷Saint Cloud, France
CH de Saint Quentin
🇫🇷Saint Quentin, France
Institut de Cancérologie
🇫🇷St Priest en Jarez, France
CH Yves Le Foll - St Brieuc
🇫🇷Saint Brieuc, France
Strasbourg Oncologie Libérale
🇫🇷Strasbourg, France
CHU de Brabois
🇫🇷Vandœuvre-lès-Nancy, France
Centre Val d'Aurélie - Paul Lamarque
🇫🇷Montpellier, France
CHU de Nice
🇫🇷Nice, France
CHU de Nîmes
🇫🇷Nîmes, France
CH de Mulhouse - Hôpital Emile Muller
🇫🇷Mulhouse Cedex, France
Hôpital Cochin
🇫🇷Paris, France
CHU de Nantes - Hôtel Dieu
🇫🇷Nantes, France
AZ St Jan Brugge Oostende AV
🇧🇪Brugge, Belgium
CHU d'Estaing
🇫🇷Clermont Ferrand, France
Pôle Santé Publique
🇫🇷Clermont Ferrand, France
Centre Catherine de Sienne
🇫🇷Nantes, France
CHRU Lille - Hôpital Claude Huriez
🇫🇷Lille, France
CHU Dupruytren - Limoges
🇫🇷Limoges, France
Centre Léon Bérard
🇫🇷Lyon, France
CH Mantes La Jolie
🇫🇷Mantes La Jolie, France
Hôpital de la Conception
🇫🇷Marseille, France
Institut Paoli Calmettes
🇫🇷Marseille, France
CH de Meaux
🇫🇷Meaux, France
Hôpital Notre Dame Bon Secours
🇫🇷Metz, France
CH Marc Jacquet
🇫🇷Melun, France
CHI de Meulan
🇫🇷Meulan en Yvelines, France
Centre Auréen de Cancérologie
🇫🇷Mougins, France
Centre Antoine Lacassagne
🇫🇷Nice Cedex 2, France
Clinique Valdegour
🇫🇷Nîmes, France
Institut Curie
🇫🇷Paris, France
APHP - Hôpital de la Pitié Salpetrière
🇫🇷Paris, France
CH Saint Jean
🇫🇷Perpignan, France
APHP - Hôpital Necker
🇫🇷Paris, France
Hospices Civils de Lyon - CHU Lyon Sud
🇫🇷Pierre Bénite, France
CHU de Haut Lévèque
🇫🇷Pessac, France
CH René Dubos
🇫🇷Pontoise, France
CHU Robert Debré
🇫🇷Reims, France
CH d'Annecy
🇫🇷Pringy, France
Institut du Cancer de Courlancy
🇫🇷Reims, France
Centre Henri Becquerel
🇫🇷Rouen, France
Clinique Mathilde
🇫🇷Rouen, France
Institut Universitaire du Cancer - Oncopole Toulouse (IUCT-O)
🇫🇷Toulouse, France
Institut Gustave Roussy
🇫🇷Villejuif, France