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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01285765
Other study ID # LNH 2009-1B
Secondary ID
Status Completed
Phase Phase 3
First received
Last updated
Start date December 2010
Est. completion date May 23, 2020

Study information

Verified date July 2020
Source The Lymphoma Academic Research Organisation
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Completed
Enrollment 650
Est. completion date May 23, 2020
Est. primary completion date May 23, 2020
Accepts healthy volunteers No
Gender All
Age group 18 Years to 80 Years
Eligibility 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.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
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

Locations

Country Name City State
Belgium ZNA Stuivenberg Antwerpen
Belgium A. Z. Sint-Jan Bruges
Belgium Institut Jules Bordet Bruxelles
Belgium Université Catholique de Louvain Saint Luc Bruxelles
Belgium Université Libre de Bruxelles - Hôpital Erasme Bruxelles
Belgium Grand Hôpital de Charleroi Charleroi
Belgium UZ Gent Gent
Belgium Hôpital Jolimont Haine Saint Paul
Belgium CHU de Liège Liege
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
France 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 Dunkerque
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 CHRU de Lille Lille
France Hôpital Saint Vincent Lille
France CHU de Limoges Limoges
France Centre Léon Bérard Lyon
France Clinique de la Sauvegarde Lyon
France Clinique Mutualiste Eugène André Lyon
France Hôpital des Chanaux Macon
France Institut Paoli Calmettes Marseille
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 de la Pitié Salpétrière Paris
France Hôpital Necker Paris
France Hôpital Saint Antoine Paris
France Hôpital Saint Antoine, Service d'hématologie du Pr Marie Paris
France Hôpital Saint Louis Paris
France Institut Curie 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 Hôpital René Huguenin Saint Cloud
France Institut de cancérologie de la Loire Saint Priest en Jarez
France CH de Saint-Brieuc - Hôpital Yves Le Foll Saint-Brieuc
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 Vandoeuvre les Nancy
France Institut Gustave Roussy Villejuif

Sponsors (2)

Lead Sponsor Collaborator
The Lymphoma Academic Research Organisation CHU de Nancy

Countries where clinical trial is conducted

Belgium,  France, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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 DELTA SUV Determine the decrease of SUV max between PET at baseline, PET after cycle 2 and PET after cycle 4 and evaluate the changes predictive interest. 3 weeks post C4 last patient
Secondary Overall Survival, EFS, response duration, DFS Assess the overall survival, the EFS (Event Free Survival - events defined as death from any cause, relapse for complete responders and undocumented complete responders, progression during or after treatment, initiation of a new anti-lymphoma therapy), the response duration, and the DFS for complete responders (disease free survival). 3 years
Secondary prognostic impact of the existence of a high tumor burden at diagnosis (> 10 cm) on PFS Evaluate the prognostic impact of the existence of a high tumor burden at diagnosis (> 10 cm). 3 years
Secondary biological factors Identify the biological factors on blood samples and on tumor biopsy influencing the patient treatment response and prognosis. 3 weeks post last cycle and 3years survival
Secondary Overall Response Rate Evaluate the overall response rate according to IWC (International Harmonization Project - Cheson 2007) (CR, PR) after 4 or 6 cycles of R-CHOP21 according to the treatment arm. 3 weeks post last cycle last patient
Secondary Rate of good responders according to results at PET after C2 Evaluate the rate of negative PET2 3 weeks post C2 last patient
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