Evaluate a Treatment Adapted to the PET Response Compared to a Standard Treatment, for Low Risk DLBCL CD 20+ Patients

NCT01285765 | Completed Phase 3 DMC

• 1 other identifier: LNH 2009-1B
• Study Type: interventional
• Target: 650
• Locations: 2 countries
• Sites: 83

Brief Summary

In this study, the investigators purpose is to evaluate the adaptation of treatment with early response based on PET scan results after 2 cycles of chemotherapy, for patient aged from 18 to 80 years, with low IPI DLBCL. This is an open randomized study. The primary endpoint is to evaluate the 3 years PFS with the aim to demonstrate the non inferiority of the experimental arm in comparison to standard arm: In standard arm, the patients will receive 6 cycles of R-CHOP 21 without taking into account of PET scan results after 2 cycles. In experimental arm, early good responder patients (defined as having a negative PET scan after 2 cycles, confirmed after 4 cycles) will receive only 4 cycles of R-CHOP 21. In both arms, if the PET scan remains positive after 4 cycles of chemotherapy, a biopsy exam is needed to confirm the failure and an intensive chemotherapy is then recommended. All of the patients, in both arms, will have an early evaluation with PET scan. All PET scan will be reviewed by a group of expert according to Deauville criteria defined by Meignan et al to adapt the decision after the 2nd cycle in experimental arm and after the 4th cycle for all patients. The final evaluation of response will be made according to 2007 Cheson's criteria.

Conditions

DLBCL

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  Evaluate by PFS at 3 years the non-inferiority of a chemotherapy treatment with 4 or 6 cycles of R-CHOP 21, determined according to early response assessed by PET at the end of 2 cycles versus standard chemotherapy of 6 cycles of R-CHOP 21 in patients with DLBCL lymphoma CD20+ with no factors of the IPI age adjusted.

  3 years

Secondary Outcomes (6)

• DELTA SUV

  3 weeks post C4 last patient

• Overall Survival, EFS, response duration, DFS

  3 years

• prognostic impact of the existence of a high tumor burden at diagnosis (> 10 cm) on PFS

  3 years

• biological factors

  3 weeks post last cycle and 3years survival

• Overall Response Rate

  3 weeks post last cycle last patient

Study Arms (2)

Early-PET-result-adapted treatment

EXPERIMENTAL

4 to 6 RCHOP21

Drug: RCHOP21

standard treatment

ACTIVE COMPARATOR

6 RCHOP21

Drug: RCHOP21

Interventions

RCHOP21 DRUG

Prednisone-60 mg/m2: D1 D2 D3 D4 D5;Rituximab-375 mg/m2 : D1; Doxorubicin-50 mg/m2 D1;Cyclophosphamide-750 mg/m2:D1 Vincristine-1.4 mg/m2 :D1; G-CSF SC -5 microg/kg/day: D6 to D13

Also known as: Rituximab-CHOP21

Early-PET-result-adapted treatment; standard treatment

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient with histologically proven CD20+ diffuse large B-cell lymphoma (DLBCL) (WHO classification 2008) including clinical subtypes (primitive mediastinal, intravascular, etc.). Patients with De Novo Transformed DLBCL from low grade lymphoma (Follicular, other...) may also be included; or CD20+ B-cell lymphoma with intermediate features between DLBCL and Burkitt; or with intermediate features between DLBCL and classical Hodgkin lymphoma; or CD20+ Follicular lymphoma grade 3B; or CD20+ Aggressive B-cell lymphoma unclassifiable.
• Age from18 to 80 years.
• Patient not previously treated.
• Ann Arbor Stage : I or II.
• Normal level of LDH.
• ECOG performance status (PS) \< 2.
• Age-adjusted international prognostic index (aaIPI) = 0.
• Baseline PET (PET0) performed before any treatment, even in absence of known lesion (for stage I for which the lesion has been removed for diagnostic reason).
• Having previously signed a written informed consent.
• The subject must be covered by a social security system (in France).

You may not qualify if:

• Any other histological type of lymphoma, Burkitt included.
• Any history of treated or non-treated small B-cell lymphoma.
• Central nervous system or meningeal involvement by lymphoma.
• Contra-indication to any drug contained in the chemotherapy regimens.
• Poor renal function (creatinin level \>150 mmol/L), poor hepatic function (total bilirubin level \>30 mmol/L, transaminases \>2.5 ULN) unless these abnormalities are related to the lymphoma.
• Poor bone marrow reserve as defined by Absolute Neutrophils Count (ANC) \<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 or women of childbearing potential not currently practicing an adequate method of contraception.
• Adult patient under tutelage.
• Impossibility to perform a baseline PET scan (PET0) before randomization and treatment start.

Sponsors & Collaborators

• The Lymphoma Academic Research Organisation: lead
• Central Hospital, Nancy, France: collaborator

Study Sites (83)

ZNA Stuivenberg

Antwerp, 2060, Belgium

Location

A. Z. Sint-Jan

Bruges, 8000, Belgium

Location

Institut Jules Bordet

Brussels, 1000, Belgium

Location

Université Libre de Bruxelles - Hôpital Erasme

Brussels, 1070, Belgium

Location

Université Catholique de Louvain Saint Luc

Brussels, 1200, Belgium

Location

Grand Hôpital de Charleroi

Charleroi, 6000, Belgium

Location

UZ Gent

Ghent, 9000, Belgium

Location

Hôpital Jolimont

Haine-Saint-Paul, 7100, Belgium

Location

CHU de Liège

Liège, 4000, Belgium

Location

Clinique Saint Joseph

Mons, 7000, Belgium

Location

Clinique Saint Pierre

Ottignies, 1340, Belgium

Location

Centre Hospitalier de Wallonie Picarde - CHwapi

Tournai, 7500, Belgium

Location

CH de la Tourelle-Peltzer

Verviers, 4800, Belgium

Location

UCL Mont Godinne

Yvoir, 5530, Belgium

Location

CHU Angers

Angers, 49033, France

Location

Centre Hospitalier Victor Dupouy

Argenteuil, 95107, France

Location

CH d'ARRAS

Arras, 62022, France

Location

CH d'Avignon

Avignon, 84902, France

Location

CH de la Côte Basque

Bayonne, 64100, France

Location

CHU de Besançon - Hôpital Jean Minjoz

Besançon, 25030, France

Location

Institut Bergonié - Bordeaux

Bordeaux, 33076, France

Location

Polyclinique Bordeaux Nord Aquitaine

Bordeaux, 33300, France

Location

CH du Dr Duchenne

Boulogne-sur-Mer, 62200, France

Location

CH de Bourg-en-Bresse

Bourg-en-Bresse, 01012, France

Location

IHBN - CHU Côte de Nacre

Caen, 14000, France

Location

CH de Cannes

Cannes, 06401, France

Location

Médipôle de Savoie

Challes-les-Eaux, 73190, France

Location

Hôpital de Chalon

Chalon-sur-Saône, 71100, France

Location

CH de Chambéry

Chambéry, 73000, France

Location

Hôpital d'Instruction des Armées Percy

Clamart, 92141, France

Location

CHU Estaing - Clermont Ferrand

Clermont-Ferrand, 63000, France

Location

Hôpital Pasteur

Colmar, 68024, France

Location

CH de Compiègne

Compiègne, 60321, France

Location

Centre Hospitalier Alpes Léman

Contamine-sur-Arve, 74130, France

Location

CH Sud Francilien

Corbeil-Essonnes, 91106, France

Location

Hôpital Henri MONDOR

Créteil, 94010, France

Location

Chu Dijon

Dijon, 21000, France

Location

CH de Dunkerque

Dunkirk, 59385, France

Location

CHU de Grenoble - Hôpital Albert Michallon

Grenoble, 38043, France

Location

CH Départemental Vendée

La Roche-sur-Yon, 85925, France

Location

CH de Versailles

Le Chesnay, 78157, France

Location

CHU Bicetre

Le Kremlin-Bicêtre, 94275, France

Location

CH de Lens

Lens, 62307, France

Location

Hôpital Saint Vincent

Lille, 59020, France

Location

CHRU de Lille

Lille, 59037, France

Location

CHU de Limoges

Limoges, 87042, France

Location

Clinique Mutualiste Eugène André

Lyon, 69003, France

Location

Clinique de la Sauvegarde

Lyon, 69009, France

Location

Centre Léon Bérard

Lyon, 69373, France

Location

Institut Paoli Calmettes

Marseille, 13273, France

Location

Hôpital des Chanaux

Mâcon, 71108, France

Location

CH de Meaux

Meaux, 77100, France

Location

CH Marc Jacquet

Melun, 77011, France

Location

Hôpital Notre Dame du Bon Secours

Metz, 57038, France

Location

CH de Mulhouse

Mulhouse, 68070, France

Location

Centre d'Oncologie de Gentilly

Nancy, 54000, France

Location

Centre Antoine Lacassagne

Nice, 06189, France

Location

CHU de Nice

Nice, 06202, France

Location

Hôpital Saint Louis

Paris, 75010, France

Location

Hôpital Saint Antoine, Service d'hématologie du Pr Marie

Paris, 75012, France

Location

Hôpital Saint Antoine

Paris, 75012, France

Location

Institut Curie

Paris, 75248, France

Location

Hôpital de la Pitié Salpétrière

Paris, 75651, France

Location

Hôpital Necker

Paris, 75743, France

Location

Hôpital LYON SUD

Pierre-Bénite, 69495, France

Location

CHU de Poitiers

Poitiers, 86021, France

Location

CH Rene Dubos

Pontoise, 95303, France

Location

CH de la Région d'Annecy

Pringy, 74370, France

Location

CHU de Reims

Reims, 51092, France

Location

CHU de Rennes - Hôpital Pontchaillou

Rennes, 35003, France

Location

Centre Hospitalier de Roubaix

Roubaix, 59100, France

Location

Centre Henri Becquerel

Rouen, 76000, France

Location

CH de Saint-Brieuc - Hôpital Yves Le Foll

Saint-Brieuc, 22023, France

Location

Hôpital René Huguenin

Saint-Cloud, 92210, France

Location

Institut de cancérologie de la Loire

Saint-Priest-en-Jarez, 42271, France

Location

CHU de Strasbourg

Strasbourg, 67098, France

Location

Hôpitaux du Leman

Thonon-les-Bains, 74203, France

Location

Hôpital Sainte Musse

Toulon, 83056, France

Location

CHU de Tours - Hôpital Bretonneau

Tours, 37044, France

Location

CH de Troyes

Troyes, 10003, France

Location

CH de Valence

Valence, 26953, France

Location

CHU Brabois

Vandœuvre-lès-Nancy, 54511, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

Related Publications (1)

• Michot JM, Bologna S, Bastie JN, Borght TV, Briere J, Ribrag V, Bommier C, Peyrade F, Lebras L, Damaj G, Coso D, Sibon D, Bonnet C, Morschhauser F, Ghesquieres H, Fruchart C, Soussain C, Becker S, Olivier P, Julian A, Molina T, Haioun C, Tilly H. Early Positron Emission Tomography Response-Adapted Treatment in Low-Risk Diffuse Large B-Cell lymphoma: an open label, multicenter, randomised, non-inferiority phase 3 trial. Ann Oncol. 2025 Nov 17:S0923-7534(25)06264-7. doi: 10.1016/j.annonc.2025.11.006. Online ahead of print.

  PMID: 41260259 DERIVED

Study Officials

• Serge Bologna, MD

  Centre d'Oncologie de Gentilly - Nancy - France

  PRINCIPAL INVESTIGATOR

• Jean-Noël BASTIE, MD

  Centre Hospitalier Universitaire Dijon

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: January 14, 2011
• First Posted: January 28, 2011
• Study Start: December 1, 2010
• Primary Completion: May 23, 2020
• Study Completion: May 23, 2020
• Last Updated: July 14, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

BE (14); FR (69)