R-CHOP + R-HAD vs R-CHOP Followed by Maintenance Lenalidomide + Rituximab vs Rituximab for Older Patients With MCL
- Conditions
- Mantle Cell Lymphoma
- Interventions
- Registration Number
- NCT01865110
- Lead Sponsor
- The Lymphoma Academic Research Organisation
- Brief 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 623
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.
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Standart induction arm R-CHOP 8 cycles of R-CHOP administered in 3 week cycles Maintenance experimental arm Rituximab lenalidomide + rituximab : 13 cycles of rituximab SC 1400 mg administered in 8 week cycles + 26 cycles Lenalidomide 15 mg 3 weeks every 4 weeks for 24 months Maintenance experimental arm Lenalidomide lenalidomide + rituximab : 13 cycles of rituximab SC 1400 mg administered in 8 week cycles + 26 cycles Lenalidomide 15 mg 3 weeks every 4 weeks for 24 months Maintenance standart arm Rituximab 13 cycles of rituximab SC 1400 mg administered in 8 week cycles for 24 months Induction experimental arm R-CHOP / R-HAD R-CHOP / R-HAD : Alternating 3 cycles of R-CHOP administered in 3 week cycles + 3 cycles of R-HAD administered in 4 week cycles.
- Primary Outcome Measures
Name Time Method Progression free survival 2.5 years 2.5 years after last patient randomized in maintenance
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (140)
Institut Gustave Roussy
🇫🇷Villejuif, France
Klinikum Nürnberg
🇩🇪Nürnberg, Germany
Brüderkrankenhaus St. Josef Paderborn
🇩🇪Paderborn, Germany
Gemini Ziekenhuis
🇳🇱Den Helder, Netherlands
Warminsko-Mazurskie Centrum Onkologii
🇵🇱Olsztyn, Poland
Institut Catala d'Oncologia (ICO) - Hospital Germans Trias y Pujol
🇪🇸Badalona, Spain
Grand Hopital de Charleroi
🇧🇪Charleroi, Belgium
Institut Bergonié
🇫🇷Bordeaux, France
AZ Groeninge
🇧🇪Kortrijk, Belgium
CHU de Liège
🇧🇪Liège, Belgium
CH de la Tourelle-Peltzer
🇧🇪Verviers, Belgium
CHU d'Angers
🇫🇷Angers, France
CHU d'Amiens
🇫🇷AMIENS Cedex 1, France
CH d Avignon - Hopital Henri Duffaut
🇫🇷Avignon Cedex 9, France
CH Côte Basque
🇫🇷Bayonne, France
CH de Blois
🇫🇷Blois, France
Hopital Antoine Beclere
🇫🇷Clamart, France
Hopital Henri Mondor
🇫🇷Creteil, France
Hospital Clínic
🇪🇸Barcelona, Spain
A. Z. Sint-Jan
🇧🇪Bruges, Belgium
ZNA Stuivenberg
🇧🇪Antwerpen, Belgium
Institut Jules Bordet
🇧🇪Bruxelles, Belgium
Université Catholique de Louvain Saint Luc
🇧🇪Bruxelles, Belgium
Université Catholique de Louvain Mont Godinne
🇧🇪Yvoir, Belgium
CHU Jean Minjoz
🇫🇷Besancon, France
Polyclinique Bordeaux Nord
🇫🇷Bordeaux, France
CH du Dr Duchenne
🇫🇷BOULOGNE SUR MER Cedex, France
CHU Morvan
🇫🇷Brest, France
MEDIPOLE de SAVOIE
🇫🇷Challes les Eaux, France
Pôle Santé République
🇫🇷CLERMONT FERRAND Cedex 2, France
CHU Caen
🇫🇷Caen, France
CH Chambéry
🇫🇷Chambery, France
CH Sud Francilien de Corbeil
🇫🇷Corbeil Essonnes, France
CHU Estaing
🇫🇷Clermont Ferrand, France
CH Départemental
🇫🇷La Roche Sur Yon, France
CHU Le Bocage
🇫🇷Dijon, France
CH Dunkerque
🇫🇷Dunkerque, France
CHU de Grenoble
🇫🇷Grenoble, France
Institut Daniel Hollard
🇫🇷GRENOBLE Cedex 1, France
Hôpital André Mignot
🇫🇷Le Chesnay, France
CH du Mans
🇫🇷Le Mans, France
CH de Lens
🇫🇷Lens, France
Clinique Victor Hugo
🇫🇷Le Mans, France
CHU Claude Hurriez
🇫🇷Lille, France
Institut Paoli Calmette
🇫🇷Marseille, France
Centre Leon Berard
🇫🇷Lyon Cedex 8, France
CH de Meaux
🇫🇷Meaux, France
CH de la Région Annecy-Genevois
🇫🇷Metz-Tessy, France
CHU Montpellier
🇫🇷MONTPELLIER Cedex 5, France
Hôpital Saint Louis
🇫🇷Paris cedex 10, France
Hôpital Bon Secours
🇫🇷Metz, France
CHR de la Source
🇫🇷ORLEANS cedex 2, France
CHU Hôtel Dieu
🇫🇷Nantes, France
CH Perpignan
🇫🇷Perpignan, France
Hopital Saint Antoine
🇫🇷Paris, France
Hôpital de la Pitié Salpêtrière
🇫🇷Paris, France
Hôpital Necker
🇫🇷Paris, France
Hôpital Haut Lévêque
🇫🇷Pessac, France
CHU Lyon Sud
🇫🇷Pierre Bénite cedex, France
CHU Robert Debre
🇫🇷Reims, France
CHU Pontchaillou
🇫🇷Rennes, France
Centre Henri Becquerel
🇫🇷Rouen, France
CH Saint Quentin
🇫🇷Saint Quentin, France
Institut de cancérologie de la Loire
🇫🇷St priest en jarez, France
CHU de Strasbourg
🇫🇷Strasbourg, France
CHU Bretonneau
🇫🇷Tours, France
CHU Nancy Brabois
🇫🇷Vandoeuvre Les Nancy, France
CHU Purpan
🇫🇷Toulouse, France
Gesundheitszentrum St. Marien GmbH
🇩🇪Amberg, Germany
Charite´ Universitätsmedizin Berlin Campus Benjamin Franklin
🇩🇪Berlin, Germany
Charite´Universitätsmedizin Berlin Campus Virchow-Klinikum
🇩🇪Berlin, Germany
Klinikum Chemnitz gGmbH
🇩🇪Chemnitz, Germany
Städt. Klinikum Braunschweig gGmbH
🇩🇪Braunschweig, Germany
DIAKO Ev. Diakonie-Krankenhaus gemeinnützige GmbH
🇩🇪Bremen, Germany
Marien Hospital Düsseldorf
🇩🇪Düsseldorf, Germany
St. Antonius Hospital
🇩🇪Eschweiler, Germany
Städt. Klinikum Karlsruhe
🇩🇪Karlsruhe, Germany
Universitätsklinikum Essen
🇩🇪Essen, Germany
Klinikum Frankfurt GmbH
🇩🇪Frankfurt (Oder), Germany
Kath. Krankenhaus Hagen gem. GmbH
🇩🇪Hagen, Germany
Uni-Klinikum-Schleswig-Holstein im Städt. Krankenhaus Kiel
🇩🇪Kiel, Germany
Universitätsklinikum Hamburg-Eppendorf
🇩🇪Hamburg, Germany
Universitätsmedizin Greifswald
🇩🇪Greifswald, Germany
Klinikum Herford
🇩🇪Herford, Germany
Universitätsklinikum des Saarlandes
🇩🇪Homburg/Saar, Germany
Internistische Praxis /Hämatologie und Onkologie
🇩🇪Kronach, Germany
Universitätsklinikum Köln
🇩🇪Köln, Germany
Klinikum Ludwigshafen
🇩🇪Ludwigshafen, Germany
Onkologisches Zentrum - Lebach
🇩🇪Lebach, Germany
Klinikum rechts der Isar der TU München
🇩🇪München, Germany
Stauferklinikum Schwäbisch Gmünd
🇩🇪Mutlangen, Germany
Kliniken Maria Hilf GmbH (Krankenhaus St. Franziskus)
🇩🇪Mönchengladbach, Germany
Klinikum der Universität München
🇩🇪München, Germany
Gemeinschaftspraxis für Hämatologie und Onkologie
🇩🇪Münster, Germany
Gemeinschaftspraxis für Hämatologie und internistische Onkologie
🇩🇪Neumarkt, Germany
Gemeinschaftspraxis für Innere Medizin, Hämatologie und internistische Onkologie
🇩🇪Offenbach, Germany
Universitätsklinikum Münster
🇩🇪Münster, Germany
Universitätsklinik Rostock
🇩🇪Rostock, Germany
University Hospital Tübingen
🇩🇪Tübingen, Germany
Mutterhaus der Borromäerinnen GmbH
🇩🇪Trier, Germany
Universitätsklinikum Ulm
🇩🇪Ulm, Germany
MC Alkmaar
🇳🇱Alkmaar, Netherlands
OLVG
🇳🇱Amsterdam, Netherlands
VUMC
🇳🇱Amsterdam, Netherlands
Amphia ziekenhuis, locatie Langendijk
🇳🇱Breda, Netherlands
Reinier de Graaf Gasthuis
🇳🇱Delft, Netherlands
Hagaziekenhuis, locatie Leyweg
🇳🇱Den Haag, Netherlands
Medisch Spectrum Twente
🇳🇱Enschede, Netherlands
Jeroen Bosch ziekenhuis
🇳🇱Den Bosch, Netherlands
Zuyderland MC
🇳🇱Geleen, Netherlands
Admiraal De Ruyter Ziekenhuis, Goes
🇳🇱Goes, Netherlands
Groene Hart Ziekenhuis
🇳🇱Gouda, Netherlands
MC Leeuwarden Zuid
🇳🇱Leeuwarden, Netherlands
Maastricht UMC
🇳🇱Maastricht, Netherlands
Spaarne ziekenhuis
🇳🇱Hoofddorp, Netherlands
UMCG
🇳🇱Groningen, Netherlands
Sint Antonius Ziekenhuis
🇳🇱Nieuwegein, Netherlands
Radboudumc
🇳🇱Nijmegen, Netherlands
Bravis ziekenhuis
🇳🇱Roosendaal, Netherlands
Erasmus MC - Daniel
🇳🇱Rotterdam, Netherlands
Erasmus MC - Centrum
🇳🇱Rotterdam, Netherlands
Maasstadziekenhuis
🇳🇱Rotterdam, Netherlands
St.Elisabeth ZH
🇳🇱Tilburg, Netherlands
Isala Klinieken, Sophia
🇳🇱Zwolle, Netherlands
Gdansk University School of Medicine
🇵🇱Gdańsk, Poland
Szpitale Wojewódzkie
🇵🇱Gdynia, Poland
University Hospital
🇵🇱Kraków, Poland
Institute of Hematology and Transfusiology
🇵🇱Warszawa, Poland
MSCM Institute and Oncology Centre
🇵🇱Warszawa, Poland
Instituto Português de Oncologia de Lisboa de Francisco Gentil
🇵🇹Lisboa, Portugal
Hospital Universitario Vall d'hebron
🇪🇸Barcelona, Spain
Hospital Universitario Fundación Alcorcón
🇪🇸Alcorcón, Spain
Hospital San Pedro de Alcántara
🇪🇸Cáceres, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Clínica Universidad de Navarra
🇪🇸Pamplona, Spain
Hospital Universitario Central de Asturias
🇪🇸Oviedo, Spain
Hospital Ramón y Cajal
🇪🇸Madrid, Spain
Hospital Clínico de Salamanca
🇪🇸Salamanca, Spain
Hospital Clinico de Valencia
🇪🇸Valencia, Spain
AMC
🇳🇱Amsterdam, Netherlands