Study of Lenalidomide Maintenance Versus Placebo in Responding Elderly Patients With DLBCL and Treated With R-CHOP

Lymphoma Clinical Trial

— REMARC  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01122472
• Other study ID #: REMARC
• Status: Completed
• Phase: Phase 3
• Start date: April 2009
• Est. completion date: September 2019

Study information

• Verified date: July 2021
• Source: The Lymphoma Academic Research Organisation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 650
• Est. completion date: September 2019
• Est. primary completion date: June 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Diffuse Large B-cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• Lenalidomide
Daily for 3 weeks every 4 weeks for 24 months
• Placebo
Daily for 3 weeks every 4 weeks for 24 months

Locations

Country	Name	City	State
Australia	Bendigo Hospital	Bendigo
Australia	Concord Repatriation General Hospital	Concord
Australia	Flinders Medical Centre - Repatriation General Hospital	Daw Park
Australia	St Vincent's Hospital, Melbourne	Fitzroy
Australia	Frankston Hospital Monash Medical Centre	Frankston
Australia	Fremantle Hospital	Fremantle
Australia	Canberra Hospital	Garran
Australia	Austin Hospital	Heidelberg
Australia	Royal Hobart Hospital	Hobart
Australia	Mater Misericordiae Hospital - Calvary Mater NewCastle	Hunter
Australia	St George Hospital	Kogarah
Australia	Sir Charles Gardiner Hospital	Nedlands
Australia	Gold Coast Hospital	Southport
Australia	Albury Base Hospital/Murray Valley Private Hospital	Wodonga
Australia	Queen Elizabeth Hospital	Woodville
Austria	LKH Feldkirch	Feldkirch
Austria	Medizinische Universität Innsbruck für Innere Medizin	Innsbruck
Austria	LKH Leoben-Eisenerz Department für Hämato-Onkologie	Leoben
Austria	AKh Linz - Innere Medizin 3 - Zentrum für Hämatologie un	Linz
Austria	Krankenhaus Barmherzigen Schwestern Linz - Abteilung für Inner	Linz
Austria	Krankenhaus der Elisabethinen Linz GmbH	Linz
Austria	Universitätklinik der PMU Salzburg - Für Innere Medizin III	Salzburg
Austria	Landeskrankenhaus Steyr - Innere Medizin II	Steyr
Austria	Uniersitätsklinik f. Innere Medizin I	Vienna
Austria	Klinikum Wels-Grieskirchen GmbH	Wels
Belgium	ZNA Middelheim	Antwerpen
Belgium	ZNA Stuivenberg	Antwerpen
Belgium	Hopital Saint Joseph	Arlon
Belgium	A.Z. Sint Jan AV	Bruges
Belgium	CHU Brugmann	Bruxelles
Belgium	Institut Jules BORDET	Bruxelles
Belgium	Universite Catholique de Louvain Saint Luc	Bruxelles
Belgium	CH Notre Dame	Charleroi
Belgium	CHU Charleroi-Vesale	Charleroi
Belgium	Centre de Sante des Fagnes	Chimay
Belgium	Universitair Ziekenhuis Gent	Gent
Belgium	Clinique Notre Dame de Grace	Gosselies
Belgium	Hopital Jolimont	Haine saint paul
Belgium	CH Hutois	HUY
Belgium	AZ VUB	Jette
Belgium	AZ Groeninge - Campus Maria s Voorzienigheid	Kortrijk
Belgium	CHR de la Citadelle	Liege
Belgium	CHU de Liege	Liege
Belgium	CHU Ambroise Pare	Mons
Belgium	Clinique Saint Joseph	Mons
Belgium	Hopital Sainte Elisabeth	Namur
Belgium	Clinique Saint Pierre	Ottignies
Belgium	Heilig Hart Ziekenhuis	Roeselare
Belgium	CH de la Tourelle-Peltzer	Verviers
Belgium	A.Z. Sint-Augustinus	Wilrijk
Belgium	Universite Catholique de Louvain Mont Godinne	Yvoir
France	CHR de la Région d'Annecy	Annecy Cedex
France	CH Antibes-Juan les Pins	Antibes
France	CH d'Arras	Arras Cedex
France	Hopital Henri DUFFAUT	Avignon
France	Hopital de BAYONNE	Bayonne
France	CHG Mail Pierre Charlot	Blois
France	Hôpital d'Avicenne	Bobigny
France	Hopital Jean VERDIER	BONDY Cedex
France	Polyclinique Bordeaux Nord Aquitaine	Bordeaux
France	Hopital DUCHENNE	Boulogne sur Mer
France	CH de Bourg-en-Bresse	Bourg-en-Bresse
France	Centre Hospitalier de Brive	Brive-La-Gaillarde
France	CHU Clémenceau- Côte de Nacre	Caen Cedex
France	Centre François Baclesse	CAEN Cedex 05
France	CH de Cannes	Cannes
France	Hôpital de Châlon	Chalon sur Saone
France	Centre Hospitalier	Chambery
France	CH Chartres	Chartres Cedex
France	Hopital Antoine Béclère	Clamart
France	Hôpital des instructions des Armées PERCY	Clamart
France	Hopital Louis Pasteur	Colmar Cedex
France	CH de Compiègne	Compiegne Cedex
France	Hopital Sud Francilien	Corbeil-Essonnes
France	CH Henri Mondor	Créteil
France	CHU le Bocage	Dijon
France	CH de Dunkerque	Dunkerque
France	CHI Evreux	Evreux
France	CHI Fréjus Saint Raphaêl	Frejus
France	Institut Daniel Hollard	Grenoble
France	Centre Hospitalier de Guéret	Gueret
France	CHG La Rochelle	La Rochelle Cedex 01
France	Hopital André Mignot	Le Chesnay
France	Hopital Bicêtre	Le Kremlin-Bicêtre
France	Clinique Victor Hugo - Centre Jean Bernard	LE Mans
France	CHU de Lens	Lens
France	Hôpital Saint Vincent de Paul	Lille
France	CHRU de Lille	Lille Cedex
France	Hopital DUPUYTREN	LIMOGES Cedex
France	Clinique de la Sauvegarde	Lyon
France	Centre Léon Bérard	LYON Cedex 08
France	CH les CHANAUX	Macon Cedex
France	Hopital Nord	Marseille
France	Institut Paoli Calmettes	Marseille Cedex
France	CHG Meaux	Meaux
France	CH Marc JACQUET	MELUN Cedex
France	Hopital Notre Dame de Bon Secours	Metz Cedex
France	CRLC Val d'Aurelle	Montpellier Cedex
France	Centre Azuréen de Cancérologie	Mougins
France	Hopital Emile Muller- CHU Mulhouse	MULHOUSE Cedex
France	Hôpital Américain de Paris	Neuilly sur seine
France	Centre Antoine Lacassagne	Nice
France	CHU de Nice	Nice
France	Hopital NECKER	Paris
France	Hopital Saint Antoine	Paris
France	Hopital St-Louis	Paris
France	Hôtel Dieu	Paris Cedex 04
France	Institut Curie	Paris Cedex 05
France	Hopital de la Pitié Salpetrière	Paris Cedex 13
France	CH de Perpignan	Perpignan
France	Centre Hospitalier Lyon Sud	Pierre Bénite Cedex
France	CH René DUBOS	Pontoise
France	Hopital Robert DEBRE	REIMS Cedex
France	Centre Henri BECQUEREL	Rouen
France	Clinique Mathilde	Rouen
France	Centre René Huguenin	Saint Cloud Cedex
France	CHG Saint Germain	St Germain en Laye
France	CHI Toulon La Seyne-sur-mer	Toulon
France	CHU Purpan Pav. Dieulafoy	Toulouse Cedex 9
France	Hopital de Troyes	Troyes Cedex
France	CH Valence	Valence Cedex 9
France	CH de Valenciennes	Valenciennes
France	CHU Nancy Brabois	Vandœuvre-lès-Nancy
France	Institut Gustave ROUSSY	VILLEJUIF Cedex
Israel	Haemek Medical Center	Afula
Israel	Barzilai Medical Center	Ashkelon
Israel	Soroka	Beer sheva
Israel	Bnai-Zion medical center	Haifa
Israel	Meir Medical Center	Kfar saba
Israel	Rabin Medical Center - Beilinson Hospital	Petah Tikwah
Israel	Kaplan Medical Center	Rehovot
Poland	SPZOZ Zespol Szpitali Miejskich w Chorzowie	Chorzow
Poland	Klinika Hematologii Collegium Medicum UJ	Krakow
Poland	Oddzial Chorob Rozrostowych Regionalny Osrodek Onkologiczny	Lodz
Poland	Medical University of Warsaw	Warsaw
Poland	Klinika Nowotworow Ukladu Chlonnego- Centrum Onkologii	Warszawa
Portugal	Hospitais da Universidade de Coimbra	Coimbra
Portugal	Hospital de Santa Maria	Lisboa
Portugal	Instituto Português de Oncologia de Lisboa de Francisco Gentil	Lisboa
Portugal	IPO - Francisco Gentil - Porto	Porto
Spain	Complejo Hospitalario Universitario de A Coruna	A coruna
Spain	Hospital Universitario Fundacion Alcorcon	Alcorcon
Spain	Hospital Clinic Barcelona	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hopital Universitario Virgen de la Arrixaca	El palmar
Spain	Hopital de Jerez (S.A.S)	Jerez de la frontera
Spain	Hospital de Leon	Leon
Spain	Hospital 12 de Octubre	Madrid
Spain	Hospital Général Universitario Gregorio Maranon	Madrid
Spain	Hospital Universitario - La Paz	Madrid
Spain	Hospital Morales Meseguer	Murcia
Spain	Hospital Central Asturias	Oviedo
Spain	Hospital Clinico Salamanca	Salamanca
Spain	Universitario Marques de Valdecilla	Santander
Spain	Hospital Joan XXIII	Tarragona
Spain	Hospital Mutua de Terrassa	Terrassa
Switzerland	Centre Hospitalier Universitaire Vaudois	Lausanne

Sponsors (1)

Lead Sponsor	Collaborator
The Lymphoma Academic Research Organisation

Countries where clinical trial is conducted

Australia,  Austria,  Belgium,  France,  Israel,  Poland,  Portugal,  Spain,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free-Survival (PFS)	PFS will be measured from the date of randomization to the date of first documented disease progression or death. Progression data will be assigned to the earliest time when any progression is observed without prior missing assessments during the study up to the end of the follow up phase.	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	Overall survival (OS)	From the date of randomization to the date of death from any cause Interim analysis of OS will be performed at the time of the PFS final analysis; it is projected to have 97 deaths at this time. Final analysis of OS at the end of the study, defined by the last visit of follow-up for the last patient randomized, 5 years after its randomization	5 years
Secondary	Event-Free Survival (EFS)	From the date of randomization to the date of first documented disease progression, relapse, initiation of new anti-lymphoma therapy or death from any cause Interim analysis of EFS will be performed at the time of the PFS final analysis. Final analysis of OS at the end of the study, defined by the last visit of follow-up for the last patient randomized, 5 years after its randomization	5 years
Secondary	Response rate at the end of maintenance treatment		24 months
Secondary	Percentage of patients who convert from PR (partial response) to CR (complete response)		24 months
Secondary	Safety of lenalidomide in maintenance	Toxicities occured during maintenance phase will be measured and reported from grade 2 for infection and neurological toxicities and from grade 3 for other toxicities according to CTCAE v3	5 years
Secondary	PFS2	From randomization to objective tumor progression on next-line treatment or death from any cause	5 years

External Links

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