Clinical trial NCT01285765: Evaluate a Treatment Adapted to the PET Response Compared to a Standard Treatment, for Low Risk DLBCL CD 20+ Patients
Official title: Randomized Phase III Study Evaluating the Non-inferiority of a Treatment Adapted to the Early Response Evaluated With 18F-FDG PET Compared to a Standard Treatment, for Patients Aged From 18 to 80 Years With Low Risk (aa IPI = 0) Diffuse Large B-cells Non Hodgkin's Lymphoma CD 20+
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: DLBCL
Lead sponsor: The Lymphoma Academic Research Organisation
Sponsor class: OTHER
Collaborators: name: Central Hospital, Nancy, France
First posted: 2011-01-28
Enrollment: 650
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Progression Free Survival
timeFrame: 3 years
Secondary outcomes:
measure: DELTA SUV
timeFrame: 3 weeks post C4 last patient
measure: Overall Survival, EFS, response duration, DFS
timeFrame: 3 years
measure: prognostic impact of the existence of a high tumor burden at diagnosis (> 10 cm) on PFS
timeFrame: 3 years
measure: biological factors
timeFrame: 3 weeks post last cycle and 3years survival
measure: Overall Response Rate
timeFrame: 3 weeks post last cycle last patient
measure: Rate of good responders according to results at PET after C2
timeFrame: 3 weeks post C2 last patient
Other outcomes:
Locations:
city: Antwerpen
country: Belgium
facility: ZNA Stuivenberg
city: Bruges
country: Belgium
facility: A. Z. Sint-Jan
city: Bruxelles
country: Belgium
facility: Institut Jules Bordet
city: Bruxelles
country: Belgium
facility: Université Libre de Bruxelles - Hôpital Erasme
city: Bruxelles
country: Belgium
facility: Université Catholique de Louvain Saint Luc
city: Charleroi
country: Belgium
facility: Grand Hôpital de Charleroi
city: Gent
country: Belgium
facility: UZ Gent
city: Haine Saint Paul
country: Belgium
facility: Hôpital Jolimont
city: Liege
country: Belgium
facility: CHU de Liège
city: Mons
country: Belgium
facility: Clinique Saint Joseph
city: Ottignies
country: Belgium
facility: Clinique Saint Pierre
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: UCL Mont Godinne
city: Angers
country: France
facility: CHU Angers
city: Argenteuil
country: France
facility: Centre Hospitalier Victor Dupouy
city: Arras
country: France
facility: CH d'ARRAS
city: Avignon
country: France
facility: CH d'Avignon
city: Bayonne
country: France
facility: CH de la Côte Basque
city: Besançon
country: France
facility: CHU de Besançon - Hôpital Jean Minjoz
city: Bordeaux
country: France
facility: Institut Bergonié - Bordeaux
city: Bordeaux
country: France
facility: Polyclinique Bordeaux Nord Aquitaine
city: Boulogne-sur-Mer
country: France
facility: CH du Dr Duchenne
city: Bourg-en-Bresse
country: France
facility: CH de Bourg-en-Bresse
city: Caen
country: France
facility: IHBN - CHU Côte de Nacre
city: Cannes
country: France
facility: CH de Cannes
city: Challes-les-Eaux
country: France
facility: Médipôle de Savoie
city: Chalon-sur-Saône
country: France
facility: Hôpital de Chalon
city: Chambéry
country: France
facility: CH de Chambéry
city: Clamart
country: France
facility: Hôpital d'Instruction des Armées Percy
city: Clermont Ferrand
country: France
facility: CHU Estaing - Clermont Ferrand
city: Colmar
country: France
facility: Hôpital Pasteur
city: Compiègne
country: France
facility: CH de Compiègne
city: Contamine-sur-Arve
country: France
facility: Centre Hospitalier Alpes Léman
city: Corbeil Essonnes
country: France
facility: CH Sud Francilien
city: Créteil
country: France
facility: Hôpital Henri MONDOR
city: Dijon
country: France
facility: Chu Dijon
city: Dunkerque
country: France
facility: CH de Dunkerque
city: Grenoble
country: France
facility: CHU de Grenoble - Hôpital Albert Michallon
city: La Roche-sur-Yon
country: France
facility: CH Départemental Vendée
city: Le Chesnay
country: France
facility: CH de Versailles
city: Le Kremlin Bicêtre
country: France
facility: CHU Bicetre
city: Lens
country: France
facility: CH de Lens
city: Lille
country: France
facility: Hôpital Saint Vincent
city: Lille
country: France
facility: CHRU de Lille
city: Limoges
country: France
facility: CHU de Limoges
city: Lyon
country: France
facility: Clinique Mutualiste Eugène André
city: Lyon
country: France
facility: Clinique de la Sauvegarde
city: Lyon
country: France
facility: Centre Léon Bérard
city: Macon
country: France
facility: Hôpital des Chanaux
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 du Bon Secours
city: Mulhouse
country: France
facility: CH de Mulhouse
city: Nancy
country: France
facility: Centre d'Oncologie de Gentilly
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Nice
country: France
facility: CHU de Nice
city: Paris
country: France
facility: Hôpital Saint Louis
city: Paris
country: France
facility: Hôpital Saint Antoine, Service d'hématologie du Pr Marie
city: Paris
country: France
facility: Hôpital Saint Antoine
city: Paris
country: France
facility: Institut Curie
city: Paris
country: France
facility: Hôpital de la Pitié Salpétrière
city: Paris
country: France
facility: Hôpital Necker
city: Pierre Bénite
country: France
facility: Hôpital LYON SUD
city: Poitiers
country: France
facility: CHU de Poitiers
city: Pontoise
country: France
facility: CH Rene Dubos
city: Pringy
country: France
facility: CH de la Région d'Annecy
city: Reims
country: France
facility: CHU de Reims
city: Rennes
country: France
facility: CHU de Rennes - Hôpital Pontchaillou
city: Roubaix
country: France
facility: Centre Hospitalier de Roubaix
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Saint Cloud
country: France
facility: Hôpital René Huguenin
city: Saint Priest en Jarez
country: France
facility: Institut de cancérologie de la Loire
city: Saint-Brieuc
country: France
facility: CH de Saint-Brieuc - Hôpital Yves Le Foll
city: Strasbourg
country: France
facility: CHU de Strasbourg
city: Thonon-les-Bains
country: France
facility: Hôpitaux du Leman
city: Toulon
country: France
facility: Hôpital Sainte Musse
city: Tours
country: France
facility: CHU de Tours - Hôpital Bretonneau
city: Troyes
country: France
facility: CH de Troyes
city: Valence
country: France
facility: CH de Valence
city: Vandoeuvre les Nancy
country: France
facility: CHU Brabois
city: Villejuif
country: France
facility: Institut Gustave Roussy
Study officials:
affiliation: Centre d'Oncologie de Gentilly - Nancy - France
name: Serge Bologna, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre Hospitalier Universitaire Dijon
name: Jean-Noël BASTIE, MD
role: PRINCIPAL_INVESTIGATOR
References: