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

NCT ID: NCT01285765

Last Updated: 2020-07-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 650 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-12-31
• Study Completion Date: 2020-05-23

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.

Detailed Description

Localized stages DLBCL with low IPI (aaIPI = 0) have a very good prognostic after a standard immuno-chemotherapy with 6 cycles of R-CHOP 21. Five years PFS is estimated over 75%, whatever the age of the patient.

PET scan is actually considered as "the gold standard" for the initial staging and the evaluation of response after treatment. With this new technique, the response criteria have been redefined by Cheson and al. in 2007. Moreover, several recent studies showed that early evaluation of response with PET scan after only 2 cycles of chemotherapy was accurate to define two groups of patients:

"Early-good-responders", when PET scan is negative "Early-poor-responders", when PET scan remains positive Prognostic for the first group is very good, and for the second poorer. At the present time, the interest of the modification and/or the intensification of the treatment for the early-poor-responder patients is not demonstrated by any publication. New studies are ongoing for patients with advanced stages of DLBC NHL (GELA trial LNH 07-3B) or Hodgkin's lymphoma (GELA and EORTC trial H10); the aim is to evaluate a new strategy of treatment adapted to early response criteria.

No trial has already been made for low IPI DLBCL. 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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Early-PET-result-adapted treatment

4 to 6 RCHOP21

Group Type: EXPERIMENTAL

RCHOP21

Intervention Type: 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

standard treatment

6 RCHOP21

Group Type: ACTIVE_COMPARATOR

RCHOP21

Intervention Type: 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

Interventions

RCHOP21

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

Intervention Type: DRUG

Other Intervention Names

Rituximab-CHOP21

Eligibility Criteria

Inclusion Criteria

• 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).

Exclusion Criteria

• 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).
• Positive HIV, HBV and HCV serologies before inclusion (except after hepatitis B vaccination or for patients who are HBs Ag negative, anti-HBs positive and/or anti-HBc positive but viral DNA negative).
• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Central Hospital, Nancy, France

OTHER

Sponsor Role: collaborator

The Lymphoma Academic Research Organisation

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Serge Bologna, MD

Role: PRINCIPAL_INVESTIGATOR

Centre d'Oncologie de Gentilly - Nancy - France

Jean-Noël BASTIE, MD

Role: PRINCIPAL_INVESTIGATOR

Centre Hospitalier Universitaire Dijon

Locations

ZNA Stuivenberg

Antwerp, , Belgium

A. Z. Sint-Jan

Bruges, , Belgium

Institut Jules Bordet

Brussels, , Belgium

Université Libre de Bruxelles - Hôpital Erasme

Brussels, , Belgium

Université Catholique de Louvain Saint Luc

Brussels, , Belgium

Grand Hôpital de Charleroi

Charleroi, , Belgium

UZ Gent

Ghent, , Belgium

Hôpital Jolimont

Haine-Saint-Paul, , Belgium

CHU de Liège

Liège, , Belgium

Clinique Saint Joseph

Mons, , Belgium

Clinique Saint Pierre

Ottignies, , Belgium

Centre Hospitalier de Wallonie Picarde - CHwapi

Tournai, , Belgium

CH de la Tourelle-Peltzer

Verviers, , Belgium

UCL Mont Godinne

Yvoir, , Belgium

CHU Angers

Angers, , France

Centre Hospitalier Victor Dupouy

Argenteuil, , France

CH d'ARRAS

Arras, , France

CH d'Avignon

Avignon, , France

CH de la Côte Basque

Bayonne, , France

CHU de Besançon - Hôpital Jean Minjoz

Besançon, , France

Institut Bergonié - Bordeaux

Bordeaux, , France

Polyclinique Bordeaux Nord Aquitaine

Bordeaux, , France

CH du Dr Duchenne

Boulogne-sur-Mer, , France

CH de Bourg-en-Bresse

Bourg-en-Bresse, , France

IHBN - CHU Côte de Nacre

Caen, , France

CH de Cannes

Cannes, , France

Médipôle de Savoie

Challes-les-Eaux, , France

Hôpital de Chalon

Chalon-sur-Saône, , France

CH de Chambéry

Chambéry, , France

Hôpital d'Instruction des Armées Percy

Clamart, , France

CHU Estaing - Clermont Ferrand

Clermont-Ferrand, , France

Hôpital Pasteur

Colmar, , France

CH de Compiègne

Compiègne, , France

Centre Hospitalier Alpes Léman

Contamine-sur-Arve, , France

CH Sud Francilien

Corbeil-Essonnes, , France

Hôpital Henri MONDOR

Créteil, , France

Chu Dijon

Dijon, , France

CH de Dunkerque

Dunkirk, , France

CHU de Grenoble - Hôpital Albert Michallon

Grenoble, , France

CH Départemental Vendée

La Roche-sur-Yon, , France

CH de Versailles

Le Chesnay, , France

CHU Bicetre

Le Kremlin-Bicêtre, , France

CH de Lens

Lens, , France

Hôpital Saint Vincent

Lille, , France

CHRU de Lille

Lille, , France

CHU de Limoges

Limoges, , France

Clinique Mutualiste Eugène André

Lyon, , France

Clinique de la Sauvegarde

Lyon, , France

Centre Léon Bérard

Lyon, , France

Institut Paoli Calmettes

Marseille, , France

Hôpital des Chanaux

Mâcon, , France

CH de Meaux

Meaux, , France

CH Marc Jacquet

Melun, , France

Hôpital Notre Dame du Bon Secours

Metz, , France

CH de Mulhouse

Mulhouse, , France

Centre d'Oncologie de Gentilly

Nancy, , France

Centre Antoine Lacassagne

Nice, , France

CHU de Nice

Nice, , France

Hôpital Saint Louis

Paris, , France

Hôpital Saint Antoine, Service d'hématologie du Pr Marie

Paris, , France

Hôpital Saint Antoine

Paris, , France

Institut Curie

Paris, , France

Hôpital de la Pitié Salpétrière

Paris, , France

Hôpital Necker

Paris, , France

Hôpital LYON SUD

Pierre-Bénite, , France

CHU de Poitiers

Poitiers, , France

CH Rene Dubos

Pontoise, , France

CH de la Région d'Annecy

Pringy, , France

CHU de Reims

Reims, , France

CHU de Rennes - Hôpital Pontchaillou

Rennes, , France

Centre Hospitalier de Roubaix

Roubaix, , France

Centre Henri Becquerel

Rouen, , France

CH de Saint-Brieuc - Hôpital Yves Le Foll

Saint-Brieuc, , France

Hôpital René Huguenin

Saint-Cloud, , France

Institut de cancérologie de la Loire

Saint-Priest-en-Jarez, , France

CHU de Strasbourg

Strasbourg, , France

Hôpitaux du Leman

Thonon-les-Bains, , France

Hôpital Sainte Musse

Toulon, , France

CHU de Tours - Hôpital Bretonneau

Tours, , France

CH de Troyes

Troyes, , France

CH de Valence

Valence, , France

CHU Brabois

Vandœuvre-lès-Nancy, , France

Institut Gustave Roussy

Villejuif, , France

Countries

Belgium; France

Other Identifiers

LNH 2009-1B

Identifier Type: -

Identifier Source: org_study_id