R-CHOP + R-HAD vs R-CHOP Followed by Maintenance Lenalidomide + Rituximab vs Rituximab for Older Patients With MCL
Conditions
Mantle Cell Lymphoma
Conditions: official terms
Lymphoma, Mantle-Cell
Conditions: Keywords
Mantle Cell Lymphoma, RCHOP, RHAD, rituximab, lenalidomide
Study Type
Interventional
Study Phase
Phase 3
Study Design
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: R-CHOP Type: Drug
Name: R-CHOP / R-HAD Type: Drug
Name: Rituximab Type: Drug
Name: Lenalidomide Type: Drug
Overall Status
Recruiting
Summary
This study aims to evaluate whether the addition of lenalidomide to rituximab-maintenance improves progression free survival (PFS) compared to standard rituximab maintenance after induction treatment consisting of R-CHOP + R-HAD vs R-CHOP alone in older patients (≥ 60 year old) with mantle cell lymphoma.

The treatments consist of two phases: induction treatment (3 R-CHOP21 + 3 cycles of R-HAD28 alternating) vs 8 cycles of R-CHOP21) followed by maintenance treatment (13 cycles of rituximab + 26 cycles of lenalidomide vs 13 cycles of rituximab).
Detailed Description
This study aims to evaluate whether the addition of lenalidomide to rituximab-maintenance improves progression free survival (PFS) compared to standard rituximab maintenance after induction treatment consisting of R-CHOP + R-HAD versus R-CHOP alone in older patients (≥ 60 year old) with mantle cell lymphoma. 643 patients will be randomized in induction phase and 433 in maintenance phase.

The treatments consist of two phases:

- induction treatment will be 3 cycles of R-CHOP21 + 3 cycles of R-HAD28(alternating) versus 8 cycles of R-CHOP21 alone

- maintenance treatment will be 13 cycles of rituximab every 8 weeks + 26 cycles of lenalidomide every 4 weeks vs 13 cycles of rituximab every 8 weeks.

Patients will be followed 2.5 years after the last patient randomized for maintenance for final analysis. All subjects who complete or discontinue the maintenance treatment for any reason will be followed for at least 3 years after his/her last study treatment administration in maintenance period for Second Primary Malignancies (SPM). A long term follow-up for progression/death will be done up to the end of period of SPM data collection.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 60 Years
Gender: Both
Criteria: Inclusion Criteria:

Signed informed consent form Biopsy-proven MCL according to WHO classification

≥ 60 years of age and ineligible for autologous transplant Ann Arbor stage II-IV Previously untreated ECOG PS ≤ 2

Male subjects must:

- agree to use a condom during sexual contact with a woman of childbearing potential, even if they have had a vasectomy, throughout lenalidomide therapy

- agree to not donate semen during lenalidomide therapy.

All subjects must:

- have an understanding that the lenalidomide could have a potential teratogenic risk.

- agree to abstain from donating blood while taking lenalidomide therapy

- agree not to share study medication with another person.

- be counselled about pregnancy precautions and risks of foetal exposure.

Additional criteria for randomization in maintenance phase:

- CR, CRu or PR after induction treatment, determined as per Cheson 1999 criteria

- During the run-in period of 6 months starting from the date of the first randomization in the trial: in case of direct randomization into maintenance phase, patient must have been treated in first line by 6-8 cycles of R-CHOP.

Exclusion Criteria:

Female of childbearing potential

Any of the following laboratory abnormalities at diagnosis, if not related to lymphoma:

Absolute neutrophils count <1,000 /mm3 Platelet count < 75,000/mm3 AST/SGOT or ALT/SGPT >3.0 UNL Serum total bilirubin > 1.5 ULN (except if due to Gilbert's syndrome) Calculated creatinine clearance (Cockcroft-Gault formula or MDRD) < 30 mL / min Central Nervous System involvement by lymphoma Contraindication for medical DVT prophylaxis for patients at high risk for DVT

Prior history of malignancies other than MCL unless the subject has been free of the disease for ≥ 5 years. Exceptions include the following:

- Basal cell carcinoma or Squamous cell carcinoma of the skin

- Carcinoma in situ of the cervix or of the breast

- Incidental histologic finding of prostate cancer (TNM stage of T1a or T1b). Any serious medical condition, laboratory abnormality or psychiatric illness that would prevent the patient to receive the study medication as planned.

Seropositivity for human immunodeficiency virus at study entry Seropositivity for hepatitis C virus at study entry,

Active viral infection with hepatitis B virus at study entry:

- HBsAg positive

- HBsAg negative, anti-HBs positive and anti-HBc positive

Uncontrolled illness including, but not limited to:

- Active infection requiring parenteral antibiotics.

- Uncontrolled diabetes mellitus

- Chronic symptomatic congestive heart failure (Class NYHA III or IV).

- Unstable angina pectoris, angioplasty, stenting, or myocardial infarction within 6 months

- Clinically significant cardiac arrhythmia that is symptomatic or requires treatment, or asymptomatic sustained ventricular tachycardia.

Prior ≥ Grade 3 allergic hypersensitivity to thalidomide. Prior ≥ Grade 3 rash or any desquamating (blistering) rash while taking thalidomide.

Known anti-murine antibody (HAMA) reactivity or known hypersensitivity to murine antibodies.

Subjects with ≥ Grade 2 neuropathy. Prior use of lenalidomide Participation in another clinical trial within three weeks before randomization in this study

Additional criteria for randomization in maintenance phase:

- SD or PD after induction treatment determined as per Cheson 1999 criteria

- Patient treated by induction immuno-chemotherapy other than 6-8 cycle of R-CHOP21 or 2-3 cycles of R-CHOP21 / 2-3 cycles of R-HAD28 (alternating)

- Patients with serious underlying medical conditions, which could impair the ability to receive maintenance treatment

- Calculated creatinine clearance of < 30 mL / min

- ANC is < 1,000 cells/mm³

- Platelet count is < 50,000 cells/mm³
Locations
ZNA Stuivenberg
Antwerpen, Belgium
Status: Not yet recruiting
Contact: Pierre ZACHEE, MD - pierre.zachee@zna.be
Institut Jules Bordet
Bruxelles, Belgium
Status: Not yet recruiting
Contact: Marie MAEREVOET, MD - marie.maerevoet@bordet.be
Université Catholique de Louvain Saint Luc
Bruxelles, Belgium
Status: Not yet recruiting
Contact: Eric VAN DEN NESTE, MD - eric.vandenneste@uclouvain.be
Grand Hopital de Charleroi
Charleroi, Belgium
Status: Not yet recruiting
Contact: Delphine PRANGER, MD - delphine.pranger@ghdc.be
AZ Groeninge
Kortrijk, Belgium
Status: Not yet recruiting
Contact: Koenraad VAN EYGEN, MD - koen.vaneygen@azgroeninge.be
CHU de Liège
Liège, Belgium
Status: Not yet recruiting
Contact: Christophe BONNET, MD - cbonnet@ulg.ac.be
CH de la Tourelle-Peltzer
Verviers, Belgium
Status: Not yet recruiting
Contact: Gaëtan VANSTRAELEN, MD - gaetan.vanstraelen@chplt.be
Université Catholique de Louvain Mont Godinne
Yvoir, Belgium
Status: Not yet recruiting
Contact: Marc ANDRE, MD - marc.andre@uclouvain.be
CHU d'Amiens
AMIENS Cedex 1, France
Status: Not yet recruiting
Contact: Jean Pierre MAROLLEAU
CHU d'Angers
Angers, France
Status: Recruiting
Contact: Marie-Pierre MOLES - mpmoles@chu-angers.fr
CH d Avignon - Hopital Henri Duffaut
Avignon Cedex 9, France
Status: Recruiting
Contact: Borhane SLAMA - Bslama@ch-avignon.fr
CH Côte Basque
Bayonne, France
Status: Recruiting
Contact: Anne BANOS - abanos@ch-cotebasque.fr
CHU Jean Minjoz
Besancon, France
Status: Recruiting
Contact: Jean FONTAN - jfontan@chu-besancon.fr
CH de Blois
Blois, France
Status: Not yet recruiting
Contact: Abderrazak EL YAMANI - elyamaa@ch-blois.fr
Institut Bergonié
Bordeaux, France
Status: Recruiting
Contact: Anna SCHMITT - a.schmitt@bordeaux.unicancer.fr
Polyclinique Bordeaux Nord
Bordeaux, France
Status: Recruiting
Contact: Olivier FITOUSSI - o.fitoussi@bordeauxnord.com
CH du Dr Duchenne
BOULOGNE SUR MER Cedex, France
Status: Recruiting
Contact: Bachra CHOUFI - b.choufi@ch-boulogne.fr
CHU Morvan
Brest, France
Status: Recruiting
Contact: Adrian TEMPESCUL - adrian.tempescul@chu-brest.fr
Centre François Baclesse
Caen, France
Status: Recruiting
Contact: Jean Pierre VILQUE
CHU Caen
Caen, France
Status: Recruiting
Contact: Margaret MACRO - macro-m@chu-caen.fr
MEDIPOLE de SAVOIE
Challes les Eaux, France
Status: Not yet recruiting
Contact: Selim CORM - selim.corm@gmail.com
CH Chambéry
Chambery, France
Status: Recruiting
Contact: Maya Hacini - maya.hacini@ch-metropole-savoie.fr
Hopital Antoine Beclere
Clamart, France
Status: Not yet recruiting
Contact: François BOUE - francois.boue@abc.aphp.fr
Pôle Santé République
CLERMONT FERRAND Cedex 2, France
Status: Recruiting
Contact: Joël FLEURY - jfleury@polesanterepublique.com
CHU Estaing
Clermont Ferrand, France
Status: Recruiting
Contact: Romain GUIEZE - rguieze@chu-clermontferrand.fr
CH Sud Francilien de Corbeil
Corbeil Essones, France
Status: Recruiting
Contact: Bertrand JOLY - bertrand.joly@ch-sud-francilien.fr
Hopital Henri Mondor
Creteil, France
Status: Recruiting
Contact: Corinne HAIOUN - corinne.haioun@hmn.aphp.fr
CHU Le Bocage
Dijon, France
Status: Recruiting
Contact: Olivier CASASNOVAS - olivier.casasnovas@chu-dijon.fr
CH Dunkerque
Dunkerque, France
Status: Not yet recruiting
Contact: Jean Michel PIGNON - jean-michel.pignon@ch-dunkerque.fr
Institut Daniel Hollard
GRENOBLE Cedex 1, France
Status: Not yet recruiting
Contact: David ASSOULINE - d.assouline@ghm-grenoble.fr
CHU de Grenoble
Grenoble, France
Status: Recruiting
Contact: Rémy GRESSIN - rgressin@chu-grenoble.fr
CH Départemental
La Roche Sur Yon, France
Status: Recruiting
Contact: Hervé MAISONNEUVE - herve.maisonneuve@chd-vendee.fr
Hôpital André Mignot
Le Chesnay, France
Status: Recruiting
Contact: Hassan FARHAT, MD - hfarhat@ch-versailles.fr
CH du Mans
Le Mans, France
Status: Recruiting
Contact: Kamel LARIBI - klaribi@ch-lemans.fr
Clinique Victor Hugo
Le Mans, France
Status: Recruiting
Contact: Katell LE DÛ - k.ledu@cjb72.org
CH de Lens
Lens, France
Status: Recruiting
Contact: Daniela ROBU - drobu@ch-lens.fr
CHU Claude Hurriez
Lille, France
Status: Recruiting
Contact: Franck MORSCHHAUSER - franck.morschhauser@chru-lille.fr
Centre Leon Berard
Lyon Cedex 8, France
Status: Not yet recruiting
Contact: Emmanuelle NICOLAS-VIRELIZIER - emmanuelle.nicolas@lyon.unicancer.fr
Institut Paoli Calmette
Marseille, France
Status: Recruiting
Contact: Reda BOUABDALLAH - bouabdallahr@ipc.unicancer.fr
CH de Meaux
Meaux, France
Status: Not yet recruiting
Contact: Jamilé FRAYER - j-frayfer@ch-meaux.fr
CH de la Région Annecy-Genevois
Metz-Tessy, France
Status: Recruiting
Contact: Nicolas DAGUINDAU - ndaguindau@ch-annecy.fr
Hôpital Bon Secours
Metz, France
Status: Not yet recruiting
Contact: Alina ZAMFIR - a.zamfir@chr-metz-thionville.fr
CHU Montpellier
MONTPELLIER Cedex 5, France
Status: Recruiting
Contact: Guillaume CARTRON - g-cartron@chu-montpellier.fr
Centre Catherine de Sienne
Nantes, France
Status: Not yet recruiting
Contact: Jean François RAMEE
CHU Hôtel Dieu
Nantes, France
Status: Recruiting
Contact: Steven LE GOUILL - steven.legouill@chu-nantes.fr
CHR de la Source
ORLEANS cedex 2, France
Status: Not yet recruiting
Contact: Omar BENBRAHIM
Hôpital Saint Louis
Paris cedex 10, France
Status: Recruiting
Contact: Catherine THIEBLEMONT - catherine.thieblemont@sls.aphp.fr
Hopital Saint Antoine
Paris, France
Status: Not yet recruiting
Contact: Zora MARJANOVIC - zora.marjanovic@sat.aphp.fr
Hôpital de la Pitié Salpêtrière
Paris, France
Status: Not yet recruiting
Contact: Jean GABARRE - jean.gabarre@psl.aphp.fr
Hôpital Necker
Paris, France
Status: Recruiting
Contact: Richard DELARUE - richard.delarue@nck.aphp.fr
CH Perpignan
Perpignan, France
Status: Recruiting
Contact: Laurence SAHNES - laurence.sanhes@ch-perpignan.fr
Hôpital Haut Lévêque
Pessac, France
Status: Recruiting
Contact: Krimo BOUABDALLAH - krimo.bouabdallah@chu-bordeaux.fr
CHU Lyon Sud
Pierre Bénite cedex, France
Status: Recruiting
Contact: Gilles SALLES - gilles.salles@chu-lyon.fr
CHU Robert Debre
Reims, France
Status: Recruiting
Contact: Alain DELMER - adelmer@chu-reims.fr
CHU Pontchaillou
Rennes, France
Status: Recruiting
Contact: Thierry LAMY de la CHAPELLE - thierry.lamy.de.la.chapelle@chu-rennes.fr
Centre Henri Becquerel
Rouen, France
Status: Recruiting
Contact: Hervé TILLY - herve.tilly@chb.unicancer.fr
CH Saint Quentin
Saint Quentin, France
Status: Recruiting
Contact: Réda GARIDI - r.garidi@ch-stquentin.fr
Institut de cancérologie de la Loire
St priest en jarez, France
Status: Recruiting
Contact: Christiane MOUNIER - christiane.mounier@icloire.fr
CHU de Strasbourg
Strasbourg, France
Status: Not yet recruiting
Contact: Luc Matthieu FORNECKER - luc-matthieu.fornecker@chru-strasbourg.fr
CHU Purpan
Toulouse, France
Status: Recruiting
Contact: Lucie OBERIC - oberic.l@chu-toulouse.fr
CHU Bretonneau
Tours, France
Status: Not yet recruiting
Contact: Caroline DARTIGEAS - c.dartigeas@chu-tours.fr
CHU Nancy Brabois
Vandoeuvre Les Nancy, France
Status: Recruiting
Contact: PIERRE FEUGIER - p.feugier@chu-nancy.fr
Institut Gustave Roussy
Villejuif, France
Status: Recruiting
Contact: Vincent RIBRAG - vincent.ribrag@gustaveroussy.fr
Gesundheitszentrum St. Marien GmbH
Amberg, Germany
Status: Not yet recruiting
Contact: Ludwig Fischer v. Weikersthal, MD
Charite´ Universitätsmedizin Berlin Campus Benjamin Franklin
Berlin, Germany
Status: Not yet recruiting
Contact: Georg Lenz, Prof.
Charite´Universitätsmedizin Berlin Campus Virchow-Klinikum
Berlin, Germany
Status: Not yet recruiting
Contact: Loew, MD
Städt. Klinikum Braunschweig gGmbH
Braunschweig, Germany
Status: Not yet recruiting
Contact: Jürgen Krauter, Prof.
DIAKO Ev. Diakonie-Krankenhaus gemeinnützige GmbH
Bremen, Germany
Status: Not yet recruiting
Contact: Johannes Kullmer, MD
Klinikum Chemnitz gGmbH
Chemnitz, Germany
Status: Not yet recruiting
Contact: Mathias Hänel, MD
St. Antonius Hospital
Eschweiler, Germany
Status: Not yet recruiting
Contact: Peter Staib, MD
Universitätsklinikum Essen
Essen, Germany
Status: Not yet recruiting
Contact: Jan Dürig, Prof.
Universitätsklinikum Frankfurt
Frankfurt, Germany
Status: Not yet recruiting
Contact: Uta Brunnberg, MD
Universitätsmedizin Greifswald
Greifswald, Germany
Status: Not yet recruiting
Contact: Christian Andreas Schmidt, Prof.
Universitätsklinikum Göttingen
Göttingen, Germany
Status: Not yet recruiting
Contact: Tobias Overbeck, MD
Kath. Krankenhaus Hagen gem. GmbH
Hagen, Germany
Status: Not yet recruiting
Contact: Hans-Walter Lindemann, MD
Asklepios Klinik St. Georg
Hamburg, Germany
Status: Not yet recruiting
Contact: Norbert Schmitz, Prof.
Universitätsklinikum Hamburg-Eppendorf
Hamburg, Germany
Status: Not yet recruiting
Contact: Judith Dierlamm, Prof.
Med. Hochschule Hannover
Hannover, Germany
Status: Not yet recruiting
Contact: Anke Franzke, Prof.
Städt. Klinikum Karlsruhe
Karlsruhe, Germany
Status: Not yet recruiting
Contact: Martin Bentz, Prof.
Uni-Klinikum-Schleswig-Holstein im Städt. Krankenhaus Kiel
Kiel, Germany
Status: Not yet recruiting
Contact: Christiane Pott, MD
Internistische Praxis /Hämatologie und Onkologie
Kronach, Germany
Status: Not yet recruiting
Contact: Martina Stauch, MD
Universitätsklinikum Köln
Köln, Germany
Status: Not yet recruiting
Contact: Kai Hübel, Prof.
Klinikum Ludwigshafen
Ludwigshafen, Germany
Status: Not yet recruiting
Contact: Martin Hoffmann, MD
Onco Studies Lörrach an der Onkologie Dreilandereck
Lörrach, Germany
Status: Not yet recruiting
Contact: Jan Knoblich, MD
Universitätsklinikum Schleswig-Holstein/Campus Lübeck
Lübeck, Germany
Status: Not yet recruiting
Contact: Harald Biersack, MD
Stauferklinikum Schwäbisch Gmünd
Mutlangen, Germany
Status: Not yet recruiting
Contact: Holger Hebart, Prof.
Kliniken Maria Hilf GmbH (Krankenhaus St. Franziskus)
Mönchengladbach, Germany
Status: Not yet recruiting
Contact: Ullrich Graeven, Prof.
Klinikum der Universität München
München, Germany
Status: Not yet recruiting
Contact: Martin Dreyling, Prof.
Klinikum rechts der Isar der TU München
München, Germany
Status: Not yet recruiting
Contact: Ulrich Keller, Prof.
Gemeinschaftspraxis für Hämatologie und Onkologie
Münster, Germany
Status: Not yet recruiting
Contact: Rüdiger Liersch, MD
Universitätsklinikum Münster
Münster, Germany
Status: Not yet recruiting
Contact: Christoph Schliemann, MD
Gemeinschaftspraxis für Hämatologie und internistische Onkologie
Neumarkt, Germany
Status: Not yet recruiting
Contact: Ekkehart Ladda, MD
Klinikum Nürnberg
Nürnberg, Germany
Status: Not yet recruiting
Contact: Josef Birkmann, MD
Gemeinschaftspraxis für Innere Medizin, Hämatologie und internistische Onkologie
Offenbach, Germany
Status: Not yet recruiting
Contact: Hans-Peter Böck, MD
Brüderkrankenhaus St. Josef Paderborn
Paderborn, Germany
Status: Not yet recruiting
Contact: Tobias Gaska, MD
Universitätsklinik Rostock
Rostock, Germany
Status: Not yet recruiting
Contact: Christina Große-Thie, MD
Diakonieklinikum Stuttgart
Stuttgart, Germany
Status: Not yet recruiting
Contact: Jochen Greiner, Prof.
Vinzenz von Paul Kliniken GmbH Marienhospital
Stuttgart, Germany
Status: Not yet recruiting
Contact: Claudio Denzlinger, Prof.
Mutterhaus der Borromäerinnen GmbH
Trier, Germany
Status: Not yet recruiting
Contact: Rolf Mahlberg, MD
Universitätsklinikum Ulm
Ulm, Germany
Status: Not yet recruiting
Contact: Stephan Stilgenbauer, Prof.
Uniklinikum Würzburg
Würzburg, Germany
Status: Not yet recruiting
Contact: Horst-Dieter Hummel, MD
Instituto Português de Oncologia de Lisboa de Francisco Gentil
Lisboa, Portugal
Status: Not yet recruiting
Contact: Maria Gomes Da Silva, Prof.
Start Date
November 2013
Completion Date
March 2024
Sponsors
The Lymphoma Academic Research Organisation
Source
The Lymphoma Academic Research Organisation
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page