Clinical trial NCT01122472: Study of Lenalidomide Maintenance Versus Placebo in Responding Elderly Patients With DLBCL and Treated With R-CHOP
Official title: Double Blind Randomized Phase III Study of Lenalidomide Maintenance Versus Placebo in Responding Elderly Patients With DLBCL and Treated With R-CHOP in First Line
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Lymphoma
Diffuse Large B-cell Lymphoma
Keywords: lenalidomide (Revlimid)
diffuse large B-cell lymphoma
phase III study
after R-CHOP
Maintenance treatment
Maintenance
Lead sponsor: The Lymphoma Academic Research Organisation
Sponsor class: OTHER
First posted: 2010-05-13
Enrollment: 650
Sex: ALL
Minimum age (years): 60
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is designed as a phase III, randomized, double-blind, placebo-controlled trial to explore the effect of maintenance therapy with lenalidomide versus placebo on progression-free survival (PFS) in patients treated with R-CHOP responding to induction therapy

For the primary efficacy variable, PFS, an improvement in median PFS from 38.6 months for Treatment Arm B to 54 months for Treatment Arm A (corresponding to a 2-year PFS of 65% vs 73.6%), is considered clinically relevant.

Detailed description: Patients should have received at least 6 and up to 8 cycles of the R-CHOP 14 or R-CHOP 21 regimen or 6 R-CHOP-14 or -21 completed by 2 Rituximab alone in accordance to local preferences.

Patients can be registered to participate in the study at two time points:

* At time of initial diagnosis and study enrolment (signature of informed consent) before the first cycle of treatment with R-CHOP.
* At randomization (signature of informed consent) after treatment in first line with R-CHOP and have reached at least PR or CR.

Evaluation of the response to R-CHOP must be in accordance with Revised Response Criteria for Malignant Lymphoma(2007).

Stratification: Before randomization, the patients will be stratified according to the country and the response to R-CHOP (PR vs CR).

Randomization: Patients in CR/PR after R-CHOP will be randomized to maintenance therapy with lenalidomide or placebo.

Eligibility criteria: Ages Eligible for Study: Between 60 and 80 years old

Genders Eligible for Study: Both

Accepts Healthy Volunteers: No

Inclusion Criteria:

For patients registered at the time of initial diagnosis

* Patient with histologically proven CD20+ diffuse large B cel LYMPHOMA (DLBCL) 5WHO 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. Patients with DLBCL associated with some small cell infiltration in bone marrow 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
* previous untreated with chemo- or radiotherapy

For patients registered after response evaluation to first line treatment with R-CHOP:

* Patient with histologically proven CD20+ diffuse large B cell LYMPHOMA (DLBCL) 5WHO 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. Patients with DLBCL associated with some small cell infiltration in bone marrow 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
* Have reached a CR or PR after first line treatment with at least 6 cycles of R-CHOP 14 regimens and up to 8 cycles of R-CHOP21
* Previously untreated with Radiotherapy

For all patients:

* aged from 60 to 80 years at time of registration
* Ann Arbor stages II-IV at time of initial diagnosis
* aaIPI\> 1 at time of initial diagnosis
* ECOG performance status 0-2
* Minimum life expectancy of 3 months
* Following laboratory values at screening:

  * ANC≥ 1000.10\^6/L and Platelets≥60000.10\^6/L
  * AST\<5\*ULN, ALT\<5\*ULN, Total Bilirubin\<1,5\*ULN
  * Creatinine clearance\>30mL/min
* Women are are using effective contraception, are not pregnant and agree not to become pregnant during participation in the trial and after end of study. Men agree not to father a child during participation in the trial and during the 12 months thereafter.
* Having previously signed a written informed consent form

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
* Contraindication to any drug contained in the chemotherapy regimen Myocardial infarction during last 3 months or unstable coronary disease or uncontrolled chronic symptomatic congestive heart insufficiency NYHA III-IV
* Uncontrolled hypertension
* Uncontrolled diabetes mellitus as defined by the investigator
* Active systemic infection requiring treatment
* previously known HIV positive serology
* Active hepatitis B or C
* Prior history of malignancies other than lymphoma within 3 years
* Serious medical or psychiatric illness

Primary outcomes:
measure: Progression-Free-Survival (PFS)
timeFrame: Final PFS analysis will be realized when the number of events (160) has been reached or at the latest when the last patient into the study will finish follow up. The approximate schedule will be 75 months after the first patient randomized.
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: 5 years
measure: Event-Free Survival (EFS)
timeFrame: 5 years
measure: Response rate at the end of maintenance treatment
timeFrame: 24 months
measure: Percentage of patients who convert from PR (partial response) to CR (complete response)
timeFrame: 24 months
measure: Safety of lenalidomide in maintenance
timeFrame: 5 years
measure: PFS2
timeFrame: 5 years
Other outcomes:
Locations:
city: Bendigo
country: Australia
facility: Bendigo Hospital
city: Concord
country: Australia
facility: Concord Repatriation General Hospital
city: Daw Park
country: Australia
facility: Flinders Medical Centre - Repatriation General Hospital
city: Fitzroy
country: Australia
facility: St Vincent's Hospital, Melbourne
city: Frankston
country: Australia
facility: Frankston Hospital Monash Medical Centre
city: Fremantle
country: Australia
facility: Fremantle Hospital
city: Garran
country: Australia
facility: Canberra Hospital
city: Heidelberg
country: Australia
facility: Austin Hospital
city: Hobart
country: Australia
facility: Royal Hobart Hospital
city: Hunter
country: Australia
facility: Mater Misericordiae Hospital - Calvary Mater NewCastle
city: Kogarah
country: Australia
facility: St George Hospital
city: Nedlands
country: Australia
facility: Sir Charles Gardiner Hospital
city: Southport
country: Australia
facility: Gold Coast Hospital
city: Wodonga
country: Australia
facility: Albury Base Hospital/Murray Valley Private Hospital
city: Woodville
country: Australia
facility: Queen Elizabeth Hospital
city: Feldkirch
country: Austria
facility: LKH Feldkirch
city: Innsbruck
country: Austria
facility: Medizinische Universität Innsbruck für Innere Medizin
city: Leoben
country: Austria
facility: LKH Leoben-Eisenerz Department für Hämato-Onkologie
city: Linz
country: Austria
facility: Krankenhaus Barmherzigen Schwestern Linz - Abteilung für Inner
city: Linz
country: Austria
facility: Krankenhaus der Elisabethinen Linz GmbH
city: Linz
country: Austria
facility: AKh Linz - Innere Medizin 3 - Zentrum für Hämatologie un
city: Salzburg
country: Austria
facility: Universitätklinik der PMU Salzburg - Für Innere Medizin III
city: Steyr
country: Austria
facility: Landeskrankenhaus Steyr - Innere Medizin II
city: Vienna
country: Austria
facility: Uniersitätsklinik f. Innere Medizin I
city: Wels
country: Austria
facility: Klinikum Wels-Grieskirchen GmbH
city: Antwerpen
country: Belgium
facility: ZNA Middelheim
city: Antwerpen
country: Belgium
facility: ZNA Stuivenberg
city: Arlon
country: Belgium
facility: Hopital Saint Joseph
city: Bruges
country: Belgium
facility: A.Z. Sint Jan AV
city: Bruxelles
country: Belgium
facility: CHU Brugmann
city: Bruxelles
country: Belgium
facility: Institut Jules BORDET
city: Bruxelles
country: Belgium
facility: Universite Catholique de Louvain Saint Luc
city: Charleroi
country: Belgium
facility: CH Notre Dame
city: Charleroi
country: Belgium
facility: CHU Charleroi-Vesale
city: Chimay
country: Belgium
facility: Centre de Sante des Fagnes
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Gosselies
country: Belgium
facility: Clinique Notre Dame de Grace
city: Haine saint paul
country: Belgium
facility: Hopital Jolimont
city: HUY
country: Belgium
facility: CH Hutois
city: Jette
country: Belgium
facility: AZ VUB
city: Kortrijk
country: Belgium
facility: AZ Groeninge - Campus Maria s Voorzienigheid
city: Liege
country: Belgium
facility: CHR de la Citadelle
city: Liege
country: Belgium
facility: CHU de Liege
city: Mons
country: Belgium
facility: CHU Ambroise Pare
city: Mons
country: Belgium
facility: Clinique Saint Joseph
city: Namur
country: Belgium
facility: Hopital Sainte Elisabeth
city: Ottignies
country: Belgium
facility: Clinique Saint Pierre
city: Roeselare
country: Belgium
facility: Heilig Hart Ziekenhuis
city: Verviers
country: Belgium
facility: CH de la Tourelle-Peltzer
city: Wilrijk
country: Belgium
facility: A.Z. Sint-Augustinus
city: Yvoir
country: Belgium
facility: Universite Catholique de Louvain Mont Godinne
city: Annecy Cedex
country: France
facility: CHR de la Région d'Annecy
city: Antibes
country: France
facility: CH Antibes-Juan les Pins
city: Arras Cedex
country: France
facility: CH d'Arras
city: Avignon
country: France
facility: Hopital Henri DUFFAUT
city: Bayonne
country: France
facility: Hopital de BAYONNE
city: Blois
country: France
facility: CHG Mail Pierre Charlot
city: Bobigny
country: France
facility: Hôpital d'Avicenne
city: BONDY Cedex
country: France
facility: Hopital Jean VERDIER
city: Bordeaux
country: France
facility: Polyclinique Bordeaux Nord Aquitaine
city: Boulogne sur Mer
country: France
facility: Hopital DUCHENNE
city: Bourg-en-Bresse
country: France
facility: CH de Bourg-en-Bresse
city: Brive-La-Gaillarde
country: France
facility: Centre Hospitalier de Brive
city: CAEN Cedex 05
country: France
facility: Centre François Baclesse
city: Caen Cedex
country: France
facility: CHU Clémenceau- Côte de Nacre
city: Cannes
country: France
facility: CH de Cannes
city: Chalon sur Saone
country: France
facility: Hôpital de Châlon
city: Chambery
country: France
facility: Centre Hospitalier
city: Chartres Cedex
country: France
facility: CH Chartres
city: Clamart
country: France
facility: Hopital Antoine Béclère
city: Clamart
country: France
facility: Hôpital des instructions des Armées PERCY
city: Colmar Cedex
country: France
facility: Hopital Louis Pasteur
city: Compiegne Cedex
country: France
facility: CH de Compiègne
city: Corbeil-Essonnes
country: France
facility: Hopital Sud Francilien
city: Créteil
country: France
facility: CH Henri Mondor
city: Dijon
country: France
facility: CHU le Bocage
city: Dunkerque
country: France
facility: CH de Dunkerque
city: Evreux
country: France
facility: CHI Evreux
city: Frejus
country: France
facility: CHI Fréjus Saint Raphaêl
city: Grenoble
country: France
facility: Institut Daniel Hollard
city: Gueret
country: France
facility: Centre Hospitalier de Guéret
city: La Rochelle Cedex 01
country: France
facility: CHG La Rochelle
city: Le Chesnay
country: France
facility: Hopital André Mignot
city: Le Kremlin-Bicêtre
country: France
facility: Hopital Bicêtre
city: LE Mans
country: France
facility: Clinique Victor Hugo - Centre Jean Bernard
city: Lens
country: France
facility: CHU de Lens
city: Lille Cedex
country: France
facility: CHRU de Lille
city: Lille
country: France
facility: Hôpital Saint Vincent de Paul
city: LIMOGES Cedex
country: France
facility: Hopital DUPUYTREN
city: LYON Cedex 08
country: France
facility: Centre Léon Bérard
city: Lyon
country: France
facility: Clinique de la Sauvegarde
city: Macon Cedex
country: France
facility: CH les CHANAUX
city: Marseille Cedex
country: France
facility: Institut Paoli Calmettes
city: Marseille
country: France
facility: Hopital Nord
city: Meaux
country: France
facility: CHG Meaux
city: MELUN Cedex
country: France
facility: CH Marc JACQUET
city: Metz Cedex
country: France
facility: Hopital Notre Dame de Bon Secours
city: Montpellier Cedex
country: France
facility: CRLC Val d'Aurelle
city: Mougins
country: France
facility: Centre Azuréen de Cancérologie
city: MULHOUSE Cedex
country: France
facility: Hopital Emile Muller- CHU Mulhouse
city: Neuilly sur seine
country: France
facility: Hôpital Américain de Paris
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Nice
country: France
facility: CHU de Nice
city: Paris Cedex 04
country: France
facility: Hôtel Dieu
city: Paris Cedex 05
country: France
facility: Institut Curie
city: Paris Cedex 13
country: France
facility: Hopital de la Pitié Salpetrière
city: Paris
country: France
facility: Hopital Saint Antoine
city: Paris
country: France
facility: Hopital St-Louis
city: Paris
country: France
facility: Hopital NECKER
city: Perpignan
country: France
facility: CH de Perpignan
city: Pierre Bénite Cedex
country: France
facility: Centre Hospitalier Lyon Sud
city: Pontoise
country: France
facility: CH René DUBOS
city: REIMS Cedex
country: France
facility: Hopital Robert DEBRE
city: Rouen
country: France
facility: Centre Henri BECQUEREL
city: Rouen
country: France
facility: Clinique Mathilde
city: Saint Cloud Cedex
country: France
facility: Centre René Huguenin
city: St Germain en Laye
country: France
facility: CHG Saint Germain
city: Toulon
country: France
facility: CHI Toulon La Seyne-sur-mer
city: Toulouse Cedex 9
country: France
facility: CHU Purpan Pav. Dieulafoy
city: Troyes Cedex
country: France
facility: Hopital de Troyes
city: Valence Cedex 9
country: France
facility: CH Valence
city: Valenciennes
country: France
facility: CH de Valenciennes
city: Vandœuvre-lès-Nancy
country: France
facility: CHU Nancy Brabois
city: VILLEJUIF Cedex
country: France
facility: Institut Gustave ROUSSY
city: Afula
country: Israel
facility: Haemek Medical Center
city: Ashkelon
country: Israel
facility: Barzilai Medical Center
city: Beer sheva
country: Israel
facility: Soroka
city: Haifa
country: Israel
facility: Bnai-Zion medical center
city: Kfar saba
country: Israel
facility: Meir Medical Center
city: Petah Tikwah
country: Israel
facility: Rabin Medical Center - Beilinson Hospital
city: Rehovot
country: Israel
facility: Kaplan Medical Center
city: Chorzow
country: Poland
facility: SPZOZ Zespol Szpitali Miejskich w Chorzowie
city: Krakow
country: Poland
facility: Klinika Hematologii Collegium Medicum UJ
city: Lodz
country: Poland
facility: Oddzial Chorob Rozrostowych Regionalny Osrodek Onkologiczny
city: Warsaw
country: Poland
facility: Medical University of Warsaw
city: Warszawa
country: Poland
facility: Klinika Nowotworow Ukladu Chlonnego- Centrum Onkologii
city: Coimbra
country: Portugal
facility: Hospitais da Universidade de Coimbra
city: Lisboa
country: Portugal
facility: Instituto Português de Oncologia de Lisboa de Francisco Gentil
city: Lisboa
country: Portugal
facility: Hospital de Santa Maria
city: Porto
country: Portugal
facility: IPO - Francisco Gentil - Porto
city: A coruna
country: Spain
facility: Complejo Hospitalario Universitario de A Coruna
city: Alcorcon
country: Spain
facility: Hospital Universitario Fundacion Alcorcon
city: Barcelona
country: Spain
facility: Hospital Clinic Barcelona
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: El palmar
country: Spain
facility: Hopital Universitario Virgen de la Arrixaca
city: Jerez de la frontera
country: Spain
facility: Hopital de Jerez (S.A.S)
city: Leon
country: Spain
facility: Hospital de Leon
city: Madrid
country: Spain
facility: Hospital 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Général Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: Hospital Universitario - La Paz
city: Murcia
country: Spain
facility: Hospital Morales Meseguer
city: Oviedo
country: Spain
facility: Hospital Central Asturias
city: Salamanca
country: Spain
facility: Hospital Clinico Salamanca
city: Santander
country: Spain
facility: Universitario Marques de Valdecilla
city: Tarragona
country: Spain
facility: Hospital Joan XXIII
city: Terrassa
country: Spain
facility: Hospital Mutua de Terrassa
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
Study officials:
References:
citation: Cottereau AS, Meignan M, Nioche C, Capobianco N, Clerc J, Chartier L, Vercellino L, Casasnovas O, Thieblemont C, Buvat I. Risk stratification in diffuse large B-cell lymphoma using lesion dissemination and metabolic tumor burden calculated from baseline PET/CTdagger. Ann Oncol. 2021 Mar;32(3):404-411. doi: 10.1016/j.annonc.2020.11.019. Epub 2020 Dec 3.
citation: Vercellino L, Cottereau AS, Casasnovas O, Tilly H, Feugier P, Chartier L, Fruchart C, Roulin L, Oberic L, Pica GM, Ribrag V, Abraham J, Simon M, Gonzalez H, Bouabdallah R, Fitoussi O, Sebban C, Lopez-Guillermo A, Sanhes L, Morschhauser F, Trotman J, Corront B, Choufi B, Snauwaert S, Godmer P, Briere J, Salles G, Gaulard P, Meignan M, Thieblemont C. High total metabolic tumor volume at baseline predicts survival independent of response to therapy. Blood. 2020 Apr 16;135(16):1396-1405. doi: 10.1182/blood.2019003526.