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

Mantle Cell Lymphoma Clinical Trial

Official title:

Efficacy of Alternating Immunochemotherapy Consisting of R-CHOP + R-HAD vs R-CHOP Alone, Followed by Maintenance Therapy Consisting of Additional Lenalidomide + Rituximab vs Rituximab Alone for Older Patients With Mantle Cell Lymphoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01865110
• Other study ID #: MCL R2 Elderly
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: November 2013
• Est. completion date: August 2025

Study information

• Verified date: December 2023
• Source: The Lymphoma Academic Research Organisation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 623
• Est. completion date: August 2025
• Est. primary completion date: November 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Mantle-Cell
• Mantle Cell Lymphoma

Intervention

Drug:
• R-CHOP
R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) administered in 3 week cycles for 8 cycles
• 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
• Rituximab
Rituximab SC 1400 mg every 8 weeks for 24 months
• Lenalidomide
Lenalidomide 15 mg 3 weeks every 4 weeks for 24 months

Locations

Country	Name	City	State
Belgium	ZNA Stuivenberg	Antwerpen
Belgium	A. Z. Sint-Jan	Bruges
Belgium	Institut Jules Bordet	Bruxelles
Belgium	Université Catholique de Louvain Saint Luc	Bruxelles
Belgium	Grand Hopital de Charleroi	Charleroi
Belgium	AZ Groeninge	Kortrijk
Belgium	CHU de Liège	Liège
Belgium	CH de la Tourelle-Peltzer	Verviers
Belgium	Université Catholique de Louvain Mont Godinne	Yvoir
France	CHU d'Amiens	AMIENS Cedex 1
France	CHU d'Angers	Angers
France	CH d Avignon - Hopital Henri Duffaut	Avignon Cedex 9
France	CH Côte Basque	Bayonne
France	CHU Jean Minjoz	Besancon
France	CH de Blois	Blois
France	Institut Bergonié	Bordeaux
France	Polyclinique Bordeaux Nord	Bordeaux
France	CH du Dr Duchenne	BOULOGNE SUR MER Cedex
France	CHU Morvan	Brest
France	CHU Caen	Caen
France	MEDIPOLE de SAVOIE	Challes les Eaux
France	CH Chambéry	Chambery
France	Hopital Antoine Beclere	Clamart
France	CHU Estaing	Clermont Ferrand
France	Pôle Santé République	CLERMONT FERRAND Cedex 2
France	CH Sud Francilien de Corbeil	Corbeil Essonnes
France	Hopital Henri Mondor	Creteil
France	CHU Le Bocage	Dijon
France	CH Dunkerque	Dunkerque
France	CHU de Grenoble	Grenoble
France	Institut Daniel Hollard	GRENOBLE Cedex 1
France	CH Départemental	La Roche Sur Yon
France	Hôpital André Mignot	Le Chesnay
France	CH du Mans	Le Mans
France	Clinique Victor Hugo	Le Mans
France	CH de Lens	Lens
France	CHU Claude Hurriez	Lille
France	Centre Leon Berard	Lyon Cedex 8
France	Institut Paoli Calmette	Marseille
France	CH de Meaux	Meaux
France	Hôpital Bon Secours	Metz
France	CH de la Région Annecy-Genevois	Metz-Tessy
France	CHU Montpellier	MONTPELLIER Cedex 5
France	CHU Hôtel Dieu	Nantes
France	CHR de la Source	ORLEANS cedex 2
France	Hôpital de la Pitié Salpêtrière	Paris
France	Hôpital Necker	Paris
France	Hopital Saint Antoine	Paris
France	Hôpital Saint Louis	Paris cedex 10
France	CH Perpignan	Perpignan
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 Purpan	Toulouse
France	CHU Bretonneau	Tours
France	CHU Nancy Brabois	Vandoeuvre Les Nancy
France	Institut Gustave Roussy	Villejuif
Germany	Gesundheitszentrum St. Marien GmbH	Amberg
Germany	Charite´ Universitätsmedizin Berlin Campus Benjamin Franklin	Berlin
Germany	Charite´Universitätsmedizin Berlin Campus Virchow-Klinikum	Berlin
Germany	Städt. Klinikum Braunschweig gGmbH	Braunschweig
Germany	DIAKO Ev. Diakonie-Krankenhaus gemeinnützige GmbH	Bremen
Germany	Klinikum Chemnitz gGmbH	Chemnitz
Germany	Marien Hospital Düsseldorf	Düsseldorf
Germany	St. Antonius Hospital	Eschweiler
Germany	Universitätsklinikum Essen	Essen
Germany	Klinikum Frankfurt GmbH	Frankfurt (Oder)
Germany	Universitätsmedizin Greifswald	Greifswald
Germany	Kath. Krankenhaus Hagen gem. GmbH	Hagen
Germany	Universitätsklinikum Hamburg-Eppendorf	Hamburg
Germany	Klinikum Herford	Herford
Germany	Universitätsklinikum des Saarlandes	Homburg/Saar
Germany	Städt. Klinikum Karlsruhe	Karlsruhe
Germany	Uni-Klinikum-Schleswig-Holstein im Städt. Krankenhaus Kiel	Kiel
Germany	Universitätsklinikum Köln	Köln
Germany	Internistische Praxis /Hämatologie und Onkologie	Kronach
Germany	Onkologisches Zentrum - Lebach	Lebach
Germany	Klinikum Ludwigshafen	Ludwigshafen
Germany	Kliniken Maria Hilf GmbH (Krankenhaus St. Franziskus)	Mönchengladbach
Germany	Klinikum der Universität München	München
Germany	Klinikum rechts der Isar der TU München	München
Germany	Gemeinschaftspraxis für Hämatologie und Onkologie	Münster
Germany	Universitätsklinikum Münster	Münster
Germany	Stauferklinikum Schwäbisch Gmünd	Mutlangen
Germany	Gemeinschaftspraxis für Hämatologie und internistische Onkologie	Neumarkt
Germany	Klinikum Nürnberg	Nürnberg
Germany	Gemeinschaftspraxis für Innere Medizin, Hämatologie und internistische Onkologie	Offenbach
Germany	Brüderkrankenhaus St. Josef Paderborn	Paderborn
Germany	Universitätsklinik Rostock	Rostock
Germany	Mutterhaus der Borromäerinnen GmbH	Trier
Germany	University Hospital Tübingen	Tübingen
Germany	Universitätsklinikum Ulm	Ulm
Netherlands	MC Alkmaar	Alkmaar
Netherlands	AMC	Amsterdam
Netherlands	OLVG	Amsterdam
Netherlands	VUMC	Amsterdam
Netherlands	Amphia ziekenhuis, locatie Langendijk	Breda
Netherlands	Reinier de Graaf Gasthuis	Delft
Netherlands	Jeroen Bosch ziekenhuis	Den Bosch
Netherlands	Hagaziekenhuis, locatie Leyweg	Den Haag
Netherlands	Gemini Ziekenhuis	Den Helder
Netherlands	Medisch Spectrum Twente	Enschede
Netherlands	Zuyderland MC	Geleen
Netherlands	Admiraal De Ruyter Ziekenhuis, Goes	Goes
Netherlands	Groene Hart Ziekenhuis	Gouda
Netherlands	UMCG	Groningen
Netherlands	Spaarne ziekenhuis	Hoofddorp
Netherlands	MC Leeuwarden Zuid	Leeuwarden
Netherlands	Maastricht UMC	Maastricht
Netherlands	Sint Antonius Ziekenhuis	Nieuwegein
Netherlands	Radboudumc	Nijmegen
Netherlands	Bravis ziekenhuis	Roosendaal
Netherlands	Erasmus MC - Centrum	Rotterdam
Netherlands	Erasmus MC - Daniel	Rotterdam
Netherlands	Maasstadziekenhuis	Rotterdam
Netherlands	St.Elisabeth ZH	Tilburg
Netherlands	Isala Klinieken, Sophia	Zwolle
Poland	Gdansk University School of Medicine	Gdansk
Poland	Szpitale Wojewódzkie	Gdynia
Poland	University Hospital	Kraków
Poland	Warminsko-Mazurskie Centrum Onkologii	Olsztyn
Poland	Institute of Hematology and Transfusiology	Warszawa
Poland	MSCM Institute and Oncology Centre	Warszawa
Portugal	Instituto Português de Oncologia de Lisboa de Francisco Gentil	Lisboa
Spain	Hospital Universitario Fundación Alcorcón	Alcorcón
Spain	Institut Catala d'Oncologia (ICO) - Hospital Germans Trias y Pujol	Badalona
Spain	Hospital Clínic	Barcelona
Spain	Hospital Universitario Vall d'hebron	Barcelona
Spain	Hospital San Pedro de Alcántara	Cáceres
Spain	Hospital Ramón y Cajal	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Central de Asturias	Oviedo
Spain	Clínica Universidad de Navarra	Pamplona
Spain	Hospital Clínico de Salamanca	Salamanca
Spain	Hospital Clinico de Valencia	Valencia

Sponsors (1)

Lead Sponsor	Collaborator
The Lymphoma Academic Research Organisation

Countries where clinical trial is conducted

Belgium,  France,  Germany,  Netherlands,  Poland,  Portugal,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression free survival	2.5 years after last patient randomized in maintenance	2.5 years