Clinical trial NCT01358747: Study of a Treatment Driven by Early PET Response to a Treatment Not Monitored by Early PET in Patients With AA Stage 3-4 or 2B HL
Official title: Randomized Phase III Study of a Treatment Driven by Early PET Response Compared to a Treatment Not Monitored by Early PET in Patients With Ann Arbor Stage III-IV or High Risk IIB Hodgkin Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hodgkin's Lymphoma
Lead sponsor: Centre Hospitalier Universitaire Dijon
Sponsor class: OTHER
Collaborators: name: The Lymphoma Study Association
First posted: 2011-05-24
Sex: ALL
Minimum age (years): 16
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL

Brief summary: All study treatments have proven efficacy in the treatment in Hodgkin lymphoma (HL). It is hoped that patients will achieve a good response to both induction therapies consisting either of 4 cycles of BEACOPPesc (Bleomycin, Etoposide, Doxorubicin, Cyclophosphamide, Vincristine, Procarbazine, and Prednisone) or 2 cycles of BEACOPPesc plus 2 cycles of ABVD (Adriamycine, Bléomycine, Vinblastine, Décarbazine).

The use of F-FDG Position Emission Tomography performed after 2 cycles of chemotherapy (PET2) in the experimental arm will help to stratify patients in order to restrict the BEACOPPesc therapy continuation to those patients who achieved only a partial response after 2 BEACOPPesc regimen and to allow a conventional dose ABVD chemotherapy strategy for PET2 negative patients. For all patients included in the trial the achievement of a good response to induction treatment will be checked after four cycles of induction treatment including a centrally reviewed PET assessment

Patients will be randomized after verification of eligibility and before the start of the protocol treatment.Patients will be randomly assigned to the standard treatment arm not monitored by early PET, or the experimental treatment arm driven by the PET2 result.


Eligibility criteria: Inclusion Criteria:

* Patient with a first diagnosis of classical Hodgkin lymphoma according to world health organization (WHO) criteria excluding nodular lymphocyte predominant subtype
* Age of 16 to 60 years
* No previous treatment for Hodgkin lymphoma
* Ann Arbor stages:

IIB with mediastinum/thorax ≥0.33 or extra nodal localization III IV

* Baseline 18-FDG PET scan (PET0)(F-FDG Positon Emission Tomography) performed before any treatment with at least one hypermetabolic lesion
* Eastern Cooperative Oncology Group (ECOG) performance status \< 3
* With a minimum life expectancy of 3 months
* Having previously signed a written informed consent
* The patient must be covered by a social security system (in France)

Exclusion Criteria:

* Pregnant or lactating women
* Men and women of childbearing potential not practicing an adequate method of contraception during the study treatment and at least 3 months after the last study drug administration
* Any history of cancer or cancer treatment during the last 5 years with the exception of non-melanoma skin tumors or stage 0 (in situ) cervical carcinoma
* Uncontrolled infectious disease, including active HBV (hepatitis B virus) infection defined by either detection of HBs Antigen or presence of anti HBs antibody without detectable anti HBc antibody.
* HIV (Human immunodeficiency virus), HCV (hepatitis C virus) or HTLV (Human T-lymphotropic virus) serology positivity
* Abnormal liver (bilirubin \> 2,5 N) function unless abnormalities are due to AHL 2011 Protocol Version n°1.2_ 09/02/11_approved on March 11, 2011 EudraCT n°2010-022844-19 4 / 73 Hodgkin lymphoma
* Abnormal renal (Creatinin \> 150 μmol/L) function unless abnormalities are due to Hodgkin lymphoma
* Leukopenia \< 2 G/l or thrombopenia \<100 G/l unless abnormalities are due to Hodgkin lymphoma
* Severe cardio-pulmonary, or metabolic disease interfering with normal application of protocol treatment:
* Left Ejection Ventricular Fraction \<50%
* Respiratory insufficiency prohibiting bleomycin use
* Uncontrolled diabetes mellitus leading to impossibility to perform PET scan
* Impossibility to perform a baseline PET (PET0) before randomization and treatment beginning
* Incapable person

Primary outcomes:
measure: Progression free survival
timeFrame: 5 years
Secondary outcomes:
Other outcomes:
Locations:
city: Antwerpen
country: Belgium
facility: ZNA Stuivenberg
city: Arlon
country: Belgium
facility: Clinique sud Luxembourg
city: Baudour
country: Belgium
facility: RHMS
city: Bruges
country: Belgium
facility: Az Sint Jan
city: Bruxelles
country: Belgium
facility: Hôpital Erasme
city: Bruxelles
country: Belgium
facility: Ucl Bruxelles
city: Charleroi
country: Belgium
facility: Grand hôpital de Charleroi
city: Haine ST Paul
country: Belgium
facility: Hôpital Jolimont
city: Kortrljk
country: Belgium
facility: AZ Groeninge
city: Mons
country: Belgium
facility: chu Ambroise Paré
city: Mons
country: Belgium
facility: Clinique St Joseph
city: Ottignies
country: Belgium
facility: Clinique ST Pierre
city: Roeselare
country: Belgium
facility: AZ Delta
city: Tournai
country: Belgium
facility: Centre Hospitalier Wallonie Picarde
city: Verviers
country: Belgium
facility: CH tourelle Peltzer
city: Yvoir
country: Belgium
facility: Chu Mont Godinne
city: Angers
country: France
facility: CHU Angers
city: Antibes
country: France
facility: CH Antibes
city: Argenteuil
country: France
facility: CH Victor Dupouy
city: Arras
country: France
facility: CH d'Arras
city: Avignon
country: France
facility: CH Avignon - Hopital Duffaut
city: Bayonne
country: France
facility: Hopital de Bayonne
city: Bordeaux
country: France
facility: Institut Bergonié
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: Bourges Cedex
country: France
facility: CH Jacques-Coeur
city: Brest
country: France
facility: Hôpital Morvan- CHU Brest
city: Brive -la- Gaillarde
country: France
facility: Ch Brive
city: Béziers
country: France
facility: CHG Béziers
city: Caen
country: France
facility: CHU de Caen-Côte de Nacre
city: Caen
country: France
facility: Centre François Baclesse
city: Castelnau-le-Lez
country: France
facility: Clinique du Parc
city: Chalon sur saône
country: France
facility: Hôpital de Chalon
city: Chambéry
country: France
facility: CH Chambéry
city: Clamart
country: France
facility: Hopital Antoine Beclere
city: Clamart
country: France
facility: Hôpital d'instruction des Armées Percy
city: Colmar
country: France
facility: Hopitaux Civil de Colmar - Hopital Pasteur
city: Corbeil-Essonnes
country: France
facility: CH Sud Francilien
city: Créteil
country: France
facility: Hopital Henri Mondor
city: Dijon
country: France
facility: CHU Dijon - Hopital du Bocage
city: Dunkerque
country: France
facility: CH de Dunkerque
city: La Roche Sur Yon
country: France
facility: Chd Vendee
city: La Rochelle Cedex 1
country: France
facility: Hopital Saint Louis
city: Le Chesnay
country: France
facility: CH de Versaille - Hopital Mignot
city: Le COUDRAY
country: France
facility: CH Chartres - Hopital Louis Pasteur
city: Le Kremelin Bicetre
country: France
facility: Hopital Bicetre
city: Le Mans
country: France
facility: Clinique Victor HUGO
city: Le Mans
country: France
facility: CHU du Mans
city: Lens
country: France
facility: CH Lens
city: Lille
country: France
facility: Chru Lille
city: Limoges
country: France
facility: CHU de Limoge - Hopital Dupuytren
city: Lyon Cedex
country: France
facility: Clinique de la Sauvegarde
city: Lyon
country: France
facility: Centre Léon Bérard
city: Marseille
country: France
facility: Institut Calmettes
city: Marseille
country: France
facility: Hopital de la conception
city: Meaux
country: France
facility: CH Meaux
city: Melun
country: France
facility: CH Marc Jacquet
city: Metz
country: France
facility: CHR Metz - Hopital Bon Secours
city: Montpellier
country: France
facility: CHU Saint-Eloi
city: Montpellier
country: France
facility: CRLC Val D'Aurelle
city: Mulhouse
country: France
facility: CH Mulhouse - Hopital Muller
city: Nantes Cedex
country: France
facility: Centre Catherine de Sienne
city: Nantes
country: France
facility: CHU Hotel Dieu
city: Neuilly sur Seine
country: France
facility: Hopital Américain de Paris
city: Nice
country: France
facility: Centre Antoine lacassagne
city: Nice
country: France
facility: CHU Nice - Hopital de l'Archet
city: Nimes
country: France
facility: CHU Caremeau
city: Orleans
country: France
facility: CHR de la Source
city: Paris Cedex 14
country: France
facility: Hopital Cochin
city: Paris
country: France
facility: Hopital Soint-Antoine
city: Paris
country: France
facility: Hôpital ST Antoine
city: Paris
country: France
facility: Institut Curie - Hopital Claudius Régaud
city: Paris
country: France
facility: Hopital Saint-Louis
city: Paris
country: France
facility: Hopital de la Pitié Salpétrière
city: Paris
country: France
facility: Hopital Necker
city: Pau Cedex
country: France
facility: CH de Pau
city: Perpignan
country: France
facility: Hôpital St Jean
city: Pessac
country: France
facility: CHU Haut Leveque - Centre François Magendie
city: Pierre Bénite
country: France
facility: CHU Lyon Sud
city: Pontoise
country: France
facility: CH Dubos
city: Pringy
country: France
facility: CH de la région d'Annecy
city: Reims
country: France
facility: CHU Reims - Hopital Robert Debré
city: Rennes
country: France
facility: Pontchaillou
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Rouen
country: France
facility: Clinique Mathilde
city: Saint Brieuc Cedex 1
country: France
facility: CH Yves Le Foll
city: Saint-Cloud
country: France
facility: Institut Curie - Hopital Huguenin
city: St Priest en Jarez
country: France
facility: Institut de Cancérologie Lucien Neuwirth
city: Strasbourg
country: France
facility: CHU de Strasbourg-Hopital de Hautepierre
city: Tours
country: France
facility: Hôpital Bretonneau
city: Troyes
country: France
facility: CH de Troyes
city: Valence
country: France
facility: CH Valence
city: Vandoeuvre les Nancy
country: France
facility: CHU Brabois
city: Vannes
country: France
facility: CH de Bretagne Atlantique
city: Villejuif
country: France
facility: Institut Gustave Roussy
Study officials:
affiliation: CHU Dijon
name: René-Olivier CASASNOVAS, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Casasnovas RO, Bouabdallah R, Brice P, Lazarovici J, Ghesquieres H, Stamatoullas A, Dupuis J, Gac AC, Gastinne T, Joly B, Bouabdallah K, Nicolas-Virelizier E, Feugier P, Morschhauser F, Sibon D, Bonnet C, Berriolo-Riedinger A, Edeline V, Parrens M, Damotte D, Coso D, Andre M, Meignan M, Rossi C. Positron Emission Tomography-Driven Strategy in Advanced Hodgkin Lymphoma: Prolonged Follow-Up of the AHL2011 Phase III Lymphoma Study Association Study. J Clin Oncol. 2022 Apr 1;40(10):1091-1101. doi: 10.1200/JCO.21.01777. Epub 2022 Jan 6.
citation: Demeestere I, Racape J, Dechene J, Dupuis J, Morschhauser F, De Wilde V, Lazarovici J, Ghesquieres H, Touati M, Sibon D, Alexis M, Gac AC, Moatti H, Virelizier E, Maisonneuve H, Pranger D, Houot R, Fornecker LM, Tempescul A, Andre M, Casasnovas RO. Gonadal Function Recovery in Patients With Advanced Hodgkin Lymphoma Treated With a PET-Adapted Regimen: Prospective Analysis of a Randomized Phase III Trial (AHL2011). J Clin Oncol. 2021 Oct 10;39(29):3251-3260. doi: 10.1200/JCO.21.00068. Epub 2021 Jun 22.
citation: Casasnovas RO, Bouabdallah R, Brice P, Lazarovici J, Ghesquieres H, Stamatoullas A, Dupuis J, Gac AC, Gastinne T, Joly B, Bouabdallah K, Nicolas-Virelizier E, Feugier P, Morschhauser F, Delarue R, Farhat H, Quittet P, Berriolo-Riedinger A, Tempescul A, Edeline V, Maisonneuve H, Fornecker LM, Lamy T, Delmer A, Dartigues P, Martin L, Andre M, Mounier N, Traverse-Glehen A, Meignan M. PET-adapted treatment for newly diagnosed advanced Hodgkin lymphoma (AHL2011): a randomised, multicentre, non-inferiority, phase 3 study. Lancet Oncol. 2019 Feb;20(2):202-215. doi: 10.1016/S1470-2045(18)30784-8. Epub 2019 Jan 15.