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

Sponsor
The Lymphoma Academic Research Organisation (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT01865110
Collaborator
(none)
623
Enrollment
140
Locations
4
Arms
141
Duration (Months)
4.5
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

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).

Condition or DiseaseIntervention/TreatmentPhase
Phase 3

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
623 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Study Start Date :
Nov 1, 2013
Actual Primary Completion Date :
Nov 30, 2020
Anticipated Study Completion Date :
Aug 1, 2025

Arms and Interventions

ArmIntervention/Treatment
Experimental: 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.

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
Other Names:
  • rituximab, CHOP
  • rituximab HD AraC
  • Active Comparator: Standart induction arm

    8 cycles of R-CHOP administered in 3 week cycles

    Drug: R-CHOP
    R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) administered in 3 week cycles for 8 cycles
    Other Names:
  • rituximab, CHOP
  • Experimental: 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

    Drug: Rituximab
    Rituximab SC 1400 mg every 8 weeks for 24 months
    Other Names:
  • Mabthera
  • Drug: Lenalidomide
    Lenalidomide 15 mg 3 weeks every 4 weeks for 24 months
    Other Names:
  • Revlimid
  • Active Comparator: Maintenance standart arm

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

    Drug: Rituximab
    Rituximab SC 1400 mg every 8 weeks for 24 months
    Other Names:
  • Mabthera
  • Outcome Measures

    Primary Outcome Measures

    1. Progression free survival [2.5 years]

      2.5 years after last patient randomized in maintenance

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    60 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1ZNA StuivenbergAntwerpenBelgium2060
    2A. Z. Sint-JanBrugesBelgium8000
    3Institut Jules BordetBruxellesBelgium1000
    4Université Catholique de Louvain Saint LucBruxellesBelgium1200
    5Grand Hopital de CharleroiCharleroiBelgium6000
    6AZ GroeningeKortrijkBelgium8500
    7CHU de LiègeLiègeBelgium4000
    8CH de la Tourelle-PeltzerVerviersBelgium4800
    9Université Catholique de Louvain Mont GodinneYvoirBelgium
    10CHU d'AmiensAMIENS Cedex 1France80054
    11CHU d'AngersAngersFrance49000
    12CH d Avignon - Hopital Henri DuffautAvignon Cedex 9France84902
    13CH Côte BasqueBayonneFrance64100
    14CHU Jean MinjozBesanconFrance25030
    15CH de BloisBloisFrance41000
    16Institut BergoniéBordeauxFrance33076
    17Polyclinique Bordeaux NordBordeauxFrance33300
    18CH du Dr DuchenneBOULOGNE SUR MER CedexFrance62321
    19CHU MorvanBrestFrance29609
    20CHU CaenCaenFrance14000
    21MEDIPOLE de SAVOIEChalles les EauxFrance73190
    22CH ChambéryChamberyFrance73011
    23Hopital Antoine BeclereClamartFrance92140
    24Pôle Santé RépubliqueCLERMONT FERRAND Cedex 2France63050
    25CHU EstaingClermont FerrandFrance63000
    26CH Sud Francilien de CorbeilCorbeil EssonnesFrance91108
    27Hopital Henri MondorCreteilFrance94010
    28CHU Le BocageDijonFrance21034
    29CH DunkerqueDunkerqueFrance59385
    30Institut Daniel HollardGRENOBLE Cedex 1France38028
    31CHU de GrenobleGrenobleFrance38043
    32CH DépartementalLa Roche Sur YonFrance85925
    33Hôpital André MignotLe ChesnayFrance78157
    34CH du MansLe MansFrance72000
    35Clinique Victor HugoLe MansFrance72000
    36CH de LensLensFrance62300
    37CHU Claude HurriezLilleFrance59037
    38Centre Leon BerardLyon Cedex 8France69373
    39Institut Paoli CalmetteMarseilleFrance13273
    40CH de MeauxMeauxFrance77104
    41CH de la Région Annecy-GenevoisMetz-TessyFrance74374
    42Hôpital Bon SecoursMetzFrance57038
    43CHU MontpellierMONTPELLIER Cedex 5France34295
    44CHU Hôtel DieuNantesFrance44093
    45CHR de la SourceORLEANS cedex 2France45067
    46Hôpital Saint LouisParis cedex 10France75475
    47Hopital Saint AntoineParisFrance75012
    48Hôpital de la Pitié SalpêtrièreParisFrance75651
    49Hôpital NeckerParisFrance75743
    50CH PerpignanPerpignanFrance66046
    51Hôpital Haut LévêquePessacFrance33604
    52CHU Lyon SudPierre Bénite cedexFrance69495
    53CHU Robert DebreReimsFrance51092
    54CHU PontchaillouRennesFrance35033
    55Centre Henri BecquerelRouenFrance76038
    56CH Saint QuentinSaint QuentinFrance02321
    57Institut de cancérologie de la LoireSt priest en jarezFrance42271
    58CHU de StrasbourgStrasbourgFrance67098
    59CHU PurpanToulouseFrance31059
    60CHU BretonneauToursFrance37044
    61CHU Nancy BraboisVandoeuvre Les NancyFrance54511
    62Institut Gustave RoussyVillejuifFrance94805
    63Gesundheitszentrum St. Marien GmbHAmbergGermany92224
    64Charite´ Universitätsmedizin Berlin Campus Benjamin FranklinBerlinGermany12200
    65Charite´Universitätsmedizin Berlin Campus Virchow-KlinikumBerlinGermany13353
    66Städt. Klinikum Braunschweig gGmbHBraunschweigGermany38114
    67DIAKO Ev. Diakonie-Krankenhaus gemeinnützige GmbHBremenGermany28239
    68Klinikum Chemnitz gGmbHChemnitzGermany9116
    69Marien Hospital DüsseldorfDüsseldorfGermany40479
    70St. Antonius HospitalEschweilerGermany52249
    71Universitätsklinikum EssenEssenGermany45147
    72Klinikum Frankfurt GmbHFrankfurt (Oder)Germany
    73Universitätsmedizin GreifswaldGreifswaldGermany17475
    74Kath. Krankenhaus Hagen gem. GmbHHagenGermany58095
    75Universitätsklinikum Hamburg-EppendorfHamburgGermany20246
    76Klinikum HerfordHerfordGermany32049
    77Universitätsklinikum des SaarlandesHomburg/SaarGermany66421
    78Städt. Klinikum KarlsruheKarlsruheGermany76133
    79Uni-Klinikum-Schleswig-Holstein im Städt. Krankenhaus KielKielGermany24116
    80Internistische Praxis /Hämatologie und OnkologieKronachGermany96317
    81Universitätsklinikum KölnKölnGermany50937
    82Onkologisches Zentrum - LebachLebachGermany66822
    83Klinikum LudwigshafenLudwigshafenGermany67063
    84Stauferklinikum Schwäbisch GmündMutlangenGermany73557
    85Kliniken Maria Hilf GmbH (Krankenhaus St. Franziskus)MönchengladbachGermany41063
    86Klinikum rechts der Isar der TU MünchenMünchenGermany81675
    87Klinikum der Universität MünchenMünchenGermany83177
    88Gemeinschaftspraxis für Hämatologie und OnkologieMünsterGermany48149
    89Universitätsklinikum MünsterMünsterGermany48149
    90Gemeinschaftspraxis für Hämatologie und internistische OnkologieNeumarktGermany92318
    91Klinikum NürnbergNürnbergGermany90419
    92Gemeinschaftspraxis für Innere Medizin, Hämatologie und internistische OnkologieOffenbachGermany63065
    93Brüderkrankenhaus St. Josef PaderbornPaderbornGermany33098
    94Universitätsklinik RostockRostockGermany18057
    95Mutterhaus der Borromäerinnen GmbHTrierGermany54219
    96University Hospital TübingenTübingenGermany72076
    97Universitätsklinikum UlmUlmGermany89081
    98MC AlkmaarAlkmaarNetherlands1800AM
    99VUMCAmsterdamNetherlands1007 MB
    100OLVGAmsterdamNetherlands1090 HM
    101AMCAmsterdamNetherlands1100 DD
    102Amphia ziekenhuis, locatie LangendijkBredaNetherlands4800 RL
    103Reinier de Graaf GasthuisDelftNetherlands2600 GA
    104Jeroen Bosch ziekenhuisDen BoschNetherlands5200 ME
    105Hagaziekenhuis, locatie LeywegDen HaagNetherlands2504 LN
    106Gemini ZiekenhuisDen HelderNetherlands1780 AT
    107Medisch Spectrum TwenteEnschedeNetherlands7500 KA
    108Zuyderland MCGeleenNetherlands6130 MB
    109Admiraal De Ruyter Ziekenhuis, GoesGoesNetherlands4460 BB
    110Groene Hart ZiekenhuisGoudaNetherlands2800 BB
    111UMCGGroningenNetherlands9700 RB
    112Spaarne ziekenhuisHoofddorpNetherlands2130 AT
    113MC Leeuwarden ZuidLeeuwardenNetherlands8901 BR
    114Maastricht UMCMaastrichtNetherlands6202 AZ
    115Sint Antonius ZiekenhuisNieuwegeinNetherlands3430 EM
    116RadboudumcNijmegenNetherlands6525 GA
    117Bravis ziekenhuisRoosendaalNetherlands4700 AZ
    118Erasmus MC - CentrumRotterdamNetherlands3000 CA
    119Erasmus MC - DanielRotterdamNetherlands3008 AE
    120MaasstadziekenhuisRotterdamNetherlands3079 DZ
    121St.Elisabeth ZHTilburgNetherlands5000 LC
    122Isala Klinieken, SophiaZwolleNetherlands8000 GK
    123Gdansk University School of MedicineGdańskPoland80-211
    124Szpitale WojewódzkieGdyniaPoland81-519
    125University HospitalKrakówPoland31-501
    126Warminsko-Mazurskie Centrum OnkologiiOlsztynPoland10-228
    127Institute of Hematology and TransfusiologyWarszawaPoland02-776
    128MSCM Institute and Oncology CentreWarszawaPoland02-781
    129Instituto Português de Oncologia de Lisboa de Francisco GentilLisboaPortugal1099-023
    130Hospital Universitario Fundación AlcorcónAlcorcónSpain28922
    131Institut Catala d'Oncologia (ICO) - Hospital Germans Trias y PujolBadalonaSpain8916
    132Hospital Universitario Vall d'hebronBarcelonaSpain8035
    133Hospital ClínicBarcelonaSpain8036
    134Hospital San Pedro de AlcántaraCáceresSpain10003
    135Hospital Ramón y CajalMadridSpain28034
    136Hospital Universitario 12 de OctubreMadridSpain28041
    137Hospital Universitario Central de AsturiasOviedoSpain33011
    138Clínica Universidad de NavarraPamplonaSpain31008
    139Hospital Clínico de SalamancaSalamancaSpain37007
    140Hospital Clinico de ValenciaValenciaSpain46010

    Sponsors and Collaborators

    • The Lymphoma Academic Research Organisation

    Investigators

    • Principal Investigator: Martin Dreyling, Prof. Dr., MCL Network
    • Principal Investigator: Vincent Ribrag, Dr, Lymphoma Study Association
    • Principal Investigator: Johanna Cornelia Kluin-Nelemans, Prof. Dr., MCL Network

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    The Lymphoma Academic Research Organisation
    ClinicalTrials.gov Identifier:
    NCT01865110
    Other Study ID Numbers:
    • MCL R2 Elderly
    First Posted:
    May 30, 2013
    Last Update Posted:
    Jul 26, 2021
    Last Verified:
    Jul 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Keywords provided by The Lymphoma Academic Research Organisation
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Jul 26, 2021