R-CHOP + R-HAD vs R-CHOP Followed by Maintenance Lenalidomide + Rituximab vs Rituximab for Older Patients With MCL

NCT ID: NCT01865110

Last Updated: 2025-03-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

623 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-11-30

Study Completion Date

2025-01-31

Brief Summary

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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

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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.

Conditions

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Mantle Cell Lymphoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Induction experimental arm

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.

Group Type EXPERIMENTAL

R-CHOP / R-HAD

Intervention Type DRUG

R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) administered in 3 week cycles for 3 cycles R-HAD (rituximab, cytarabine, dexamethasone) administered in 3 week cycles for 4 cycles alternating

Standart induction arm

8 cycles of R-CHOP administered in 3 week cycles

Group Type ACTIVE_COMPARATOR

R-CHOP

Intervention Type DRUG

R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) administered in 3 week cycles for 8 cycles

Maintenance experimental arm

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

Group Type EXPERIMENTAL

Rituximab

Intervention Type DRUG

Rituximab SC 1400 mg every 8 weeks for 24 months

Lenalidomide

Intervention Type DRUG

Lenalidomide 15 mg 3 weeks every 4 weeks for 24 months

Maintenance standart arm

13 cycles of rituximab SC 1400 mg administered in 8 week cycles for 24 months

Group Type ACTIVE_COMPARATOR

Rituximab

Intervention Type DRUG

Rituximab SC 1400 mg every 8 weeks for 24 months

Interventions

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R-CHOP

R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) administered in 3 week cycles for 8 cycles

Intervention Type DRUG

R-CHOP / R-HAD

R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) administered in 3 week cycles for 3 cycles R-HAD (rituximab, cytarabine, dexamethasone) administered in 3 week cycles for 4 cycles alternating

Intervention Type DRUG

Rituximab

Rituximab SC 1400 mg every 8 weeks for 24 months

Intervention Type DRUG

Lenalidomide

Lenalidomide 15 mg 3 weeks every 4 weeks for 24 months

Intervention Type DRUG

Other Intervention Names

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rituximab, CHOP rituximab, CHOP rituximab HD AraC Mabthera Revlimid

Eligibility Criteria

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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
Minimum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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The Lymphoma Academic Research Organisation

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Martin Dreyling, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

MCL Network

Vincent Ribrag, Dr

Role: PRINCIPAL_INVESTIGATOR

Lymphoma Study Association

Johanna Cornelia Kluin-Nelemans, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

MCL Network

Locations

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ZNA Stuivenberg

Antwerp, , Belgium

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A. Z. Sint-Jan

Bruges, , Belgium

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Institut Jules Bordet

Brussels, , Belgium

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Université Catholique de Louvain Saint Luc

Brussels, , Belgium

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Grand Hopital de Charleroi

Charleroi, , Belgium

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AZ Groeninge

Kortrijk, , Belgium

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CHU de Liège

Liège, , Belgium

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CH de la Tourelle-Peltzer

Verviers, , Belgium

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Université Catholique de Louvain Mont Godinne

Yvoir, , Belgium

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CHU d'Amiens

Amiens, , France

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CHU d'Angers

Angers, , France

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CH d Avignon - Hopital Henri Duffaut

Avignon, , France

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CH Côte Basque

Bayonne, , France

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CHU Jean Minjoz

Besançon, , France

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CH de Blois

Blois, , France

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Institut Bergonié

Bordeaux, , France

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Polyclinique Bordeaux Nord

Bordeaux, , France

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CH du Dr Duchenne

Boulogne-sur-Mer, , France

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CHU Morvan

Brest, , France

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CHU Caen

Caen, , France

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MEDIPOLE de SAVOIE

Challes-les-Eaux, , France

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CH Chambéry

Chambéry, , France

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CHU de Châlon-sur-Sâone - William Morey

Châlon-sur-Sâone, , France

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Hopital Antoine Beclere

Clamart, , France

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CHU Estaing

Clermont-Ferrand, , France

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Pôle Santé République

Clermont-Ferrand, , France

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CH Sud Francilien de Corbeil

Corbeil-Essonnes, , France

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Hopital Henri Mondor

Créteil, , France

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CHU Le Bocage

Dijon, , France

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CH Dunkerque

Dunkirk, , France

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Institut Daniel Hollard

Grenoble, , France

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CHU de Grenoble

Grenoble, , France

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CH Départemental

La Roche-sur-Yon, , France

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Groupe Hospitalier La Rochelle - Ré - Aunis

La Rochelle, , France

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Hôpital André Mignot

Le Chesnay, , France

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CH du Mans

Le Mans, , France

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Clinique Victor Hugo

Le Mans, , France

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CH de Lens

Lens, , France

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CHU Claude Hurriez

Lille, , France

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Centre Leon Berard

Lyon, , France

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Institut Paoli Calmette

Marseille, , France

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CH de Meaux

Meaux, , France

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Hôpital Bon Secours

Metz, , France

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CH de la Région Annecy-Genevois

Metz-Tessy, , France

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CHU Montpellier

Montpellier, , France

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CHU Hôtel Dieu

Nantes, , France

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CHR de la Source

Orléans, , France

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Hopital Saint Antoine

Paris, , France

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Hôpital Saint Louis

Paris, , France

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Hôpital de la Pitié Salpêtrière

Paris, , France

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Hôpital Necker

Paris, , France

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CH Perpignan

Perpignan, , France

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Hôpital Haut Lévêque

Pessac, , France

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CHU Lyon Sud

Pierre-Bénite, , France

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CH de Quimper Cornouaille

Quimper, , France

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CHU Robert Debre

Reims, , France

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CHU Pontchaillou

Rennes, , France

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Centre Henri Becquerel

Rouen, , France

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Institut de cancérologie de la Loire

Saint-Priest-en-Jarez, , France

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CH Saint Quentin

Saint-Quentin, , France

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CHU de Strasbourg

Strasbourg, , France

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CHU Purpan

Toulouse, , France

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CHU Bretonneau

Tours, , France

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CHU Nancy Brabois

Vandœuvre-lès-Nancy, , France

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Institut Gustave Roussy

Villejuif, , France

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Gesundheitszentrum St. Marien GmbH

Amberg, , Germany

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Charite´ Universitätsmedizin Berlin Campus Benjamin Franklin

Berlin, , Germany

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Charite´Universitätsmedizin Berlin Campus Virchow-Klinikum

Berlin, , Germany

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Städt. Klinikum Braunschweig gGmbH

Braunschweig, , Germany

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DIAKO Ev. Diakonie-Krankenhaus gemeinnützige GmbH

Bremen, , Germany

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Klinikum Chemnitz gGmbH

Chemnitz, , Germany

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Universitätsklinikum Köln

Cologne, , Germany

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Marien Hospital Düsseldorf

Düsseldorf, , Germany

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St. Antonius Hospital

Eschweiler, , Germany

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Universitätsklinikum Essen

Essen, , Germany

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Klinikum Frankfurt GmbH

Frankfurt (Oder), , Germany

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Universitätsmedizin Greifswald

Greifswald, , Germany

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Kath. Krankenhaus Hagen gem. GmbH

Hagen, , Germany

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Universitätsklinikum Hamburg-Eppendorf

Hamburg, , Germany

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Klinikum Herford

Herford, , Germany

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Universitätsklinikum des Saarlandes

Homburg/Saar, , Germany

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Städt. Klinikum Karlsruhe

Karlsruhe, , Germany

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Uni-Klinikum-Schleswig-Holstein im Städt. Krankenhaus Kiel

Kiel, , Germany

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Internistische Praxis /Hämatologie und Onkologie

Kronach, , Germany

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Onkologisches Zentrum - Lebach

Lebach, , Germany

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Klinikum Ludwigshafen

Ludwigshafen, , Germany

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Kliniken Maria Hilf GmbH (Krankenhaus St. Franziskus)

Mönchengladbach, , Germany

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Stauferklinikum Schwäbisch Gmünd

Mutlangen, , Germany

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Klinikum rechts der Isar der TU München

München, , Germany

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Klinikum der Universität München

München, , Germany

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Gemeinschaftspraxis für Hämatologie und Onkologie

Münster, , Germany

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Universitätsklinikum Münster

Münster, , Germany

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Gemeinschaftspraxis für Hämatologie und internistische Onkologie

Neumarkt, , Germany

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Klinikum Nürnberg

Nuremberg, , Germany

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Gemeinschaftspraxis für Innere Medizin, Hämatologie und internistische Onkologie

Offenbach, , Germany

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Brüderkrankenhaus St. Josef Paderborn

Paderborn, , Germany

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Universitätsklinik Rostock

Rostock, , Germany

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Mutterhaus der Borromäerinnen GmbH

Trier, , Germany

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University Hospital Tübingen

Tübingen, , Germany

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Universitätsklinikum Ulm

Ulm, , Germany

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Jeroen Bosch ziekenhuis

's-Hertogenbosch, , Netherlands

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MC Alkmaar

Alkmaar, , Netherlands

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VUMC

Amsterdam, , Netherlands

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OLVG

Amsterdam, , Netherlands

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AMC

Amsterdam, , Netherlands

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Amphia ziekenhuis, locatie Langendijk

Breda, , Netherlands

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Reinier de Graaf Gasthuis

Delft, , Netherlands

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Gemini Ziekenhuis

Den Helder, , Netherlands

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Medisch Spectrum Twente

Enschede, , Netherlands

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Zuyderland MC

Geleen, , Netherlands

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Admiraal De Ruyter Ziekenhuis, Goes

Goes, , Netherlands

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Groene Hart Ziekenhuis

Gouda, , Netherlands

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UMCG

Groningen, , Netherlands

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Spaarne ziekenhuis

Hoofddorp, , Netherlands

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MC Leeuwarden Zuid

Leeuwarden, , Netherlands

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Maastricht UMC

Maastricht, , Netherlands

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Sint Antonius Ziekenhuis

Nieuwegein, , Netherlands

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Radboudumc

Nijmegen, , Netherlands

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Bravis ziekenhuis

Roosendaal, , Netherlands

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Erasmus MC - Centrum

Rotterdam, , Netherlands

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Erasmus MC - Daniel

Rotterdam, , Netherlands

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Maasstadziekenhuis

Rotterdam, , Netherlands

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Hagaziekenhuis, locatie Leyweg

The Hague, , Netherlands

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St.Elisabeth ZH

Tilburg, , Netherlands

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Isala Klinieken, Sophia

Zwolle, , Netherlands

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Gdansk University School of Medicine

Gdansk, , Poland

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Szpitale Wojewódzkie

Gdynia, , Poland

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University Hospital

Krakow, , Poland

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Warminsko-Mazurskie Centrum Onkologii

Olsztyn, , Poland

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Institute of Hematology and Transfusiology

Warsaw, , Poland

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MSCM Institute and Oncology Centre

Warsaw, , Poland

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Instituto Português de Oncologia de Lisboa de Francisco Gentil

Lisbon, , Portugal

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Hospital Universitario Fundación Alcorcón

Alcorcón, , Spain

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Institut Catala d'Oncologia (ICO) - Hospital Germans Trias y Pujol

Badalona, , Spain

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Hospital Universitario Vall d'hebron

Barcelona, , Spain

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Hospital Clínic

Barcelona, , Spain

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Hospital San Pedro de Alcántara

Cáceres, , Spain

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Hospital Ramón y Cajal

Madrid, , Spain

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Hospital Universitario 12 de Octubre

Madrid, , Spain

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Hospital Universitario Central de Asturias

Oviedo, , Spain

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Clínica Universidad de Navarra

Pamplona, , Spain

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Hospital Clínico de Salamanca

Salamanca, , Spain

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Hospital Clinico de Valencia

Valencia, , Spain

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Countries

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Belgium France Germany Netherlands Poland Portugal Spain

Other Identifiers

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MCL R2 Elderly

Identifier Type: -

Identifier Source: org_study_id

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