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

DLBCL Clinical Trial

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+

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01285765
• Other study ID #: LNH 2009-1B
• Status: Completed
• Phase: Phase 3
• 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
• 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.

Related Conditions & MeSH terms

• DLBCL

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