NCT00209209

Brief Summary

The aim of this study is to answer the following independent questions in the treatment of mantle cell lymphomas:

  • Can rituximab-fludarabine, cyclophosphamide (R-FC) improve the reduction of lymphoma mass compared to rituximab-cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) and so become a new standard for initial cytoreductive therapy?
  • Can maintenance with rituximab substitute the interferon maintenance and even improve the progression free survival in patients after successful initial cytoreductive therapy?

Trial Health

50
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
570

participants targeted

Target at P75+ for phase_3

Timeline
Completed

Started Jan 2004

Longer than P75 for phase_3

Geographic Reach
7 countries

7 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 14, 2004

Completed
1.7 years until next milestone

First Submitted

Initial submission to the registry

September 13, 2005

Completed
8 days until next milestone

First Posted

Study publicly available on registry

September 21, 2005

Completed
13.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2018

Completed
Last Updated

March 7, 2017

Status Verified

March 1, 2017

Enrollment Period

14.9 years

First QC Date

September 13, 2005

Last Update Submit

March 6, 2017

Conditions

Lymphoma, Mantle-Cell

Keywords

Lymphoma, Mantle-CellElderly patientsChemotherapyMaintenance therapyC04.557.386.480.300.725.500C15.604.515.569.480.300.725.500C20.683.515.761.480.300.725.500

Outcome Measures

Primary Outcomes (2)

  • First randomisation: Reduction of lymphoma mass measured by the complete remission (CR) rate

  • Second randomisation: progression-free survival after end of initial chemotherapy

Secondary Outcomes (6)

  • Survival after registration / first randomisation / second randomisation

  • Survival after start / end of initial therapy

  • Time to treatment failure after start of initial therapy

  • Progression free survival after registration / first randomisation / second randomisation

  • Side-effects of initial therapy

  • +1 more secondary outcomes

Study Arms (2)

1

ACTIVE COMPARATOR

1. randomisation: R-CHOP 2. randomisation: IFN maintenance

Drug: RituximabDrug: CyclophosphamideDrug: DoxorubicinDrug: VincristineDrug: PrednisoneDrug: Interferon-alphaDrug: pegylated formula Interferon-alpha 2bProcedure: chemotherapy: R-CHOPProcedure: Interferon maintenance

2

EXPERIMENTAL

1. randomisation: R-FC 2. randomisation: Rituximab maintnenance

Drug: RituximabDrug: CyclophosphamideDrug: FludarabineProcedure: chemotherapy: R-FCProcedure: Rituximab maintenance

Interventions

RituximabDRUG

antibody

12
CyclophosphamideDRUG

chemotherapy

12
DoxorubicinDRUG

chemotherapy

1
VincristineDRUG

chemotherapy

1
PrednisoneDRUG

coricosteroide

1
FludarabineDRUG

chemotherapy

2
Interferon-alphaDRUG

cytokine

1
pegylated formula Interferon-alpha 2bDRUG

cytokine

1
chemotherapy: R-CHOPPROCEDURE

immuno-chemotherapy

1
chemotherapy: R-FCPROCEDURE

immuno-chemotherapy

2
Interferon maintenancePROCEDURE

cytokine

1
Rituximab maintenancePROCEDURE

antibody

2

Eligibility Criteria

Age60 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Histologically proven mantle cell lymphoma according to the World Health Organization (WHO) classification, preferably confirmed by central pathology review before entering the study
  • Clinical stage II, III or IV
  • Previously untreated patients
  • Above the age of 65 years and older or patients at the age between 60 and 65, if not eligible for high dose chemotherapy
  • WHO performance grade 0, 1 or 2
  • Informed consent according to International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use/European Union Good Clinical Practice (ICH/EU GCP) and national/local regulations
  • Measurable disease. If, for example only bone marrow (BM) infiltration, patients can only undergo a second randomization if a CR is obtained.

You may not qualify if:

  • WHO performance of 3 or more
  • Known anti-murine antibody (HAMA) reactivity or known hypersensitivity to murine antibodies
  • Leukocytes \<2.0x 10\^9/l or thrombocytes \<100x 10\^9/l, unless clearly related to mantle cell lymphoma (MCL) bone marrow infiltration
  • Patients previously treated for lymphoma
  • Patients without measurable lesions; if, for example only bone marrow infiltration, patients may be included, but can only undergo a second randomization in case of a CR
  • Patients with stage I disease
  • Patients with central nervous system involvement
  • Patients with a history of autoimmune hemolytic anaemia or autoimmune thrombocytopenia
  • Patients with serious cardiac disease (uncontrolled arrhythmias, unstable angina, severe congestive heart failure)
  • Patients with serious pulmonary, neurological, endocrinological or other disorder interfering with full dosing of CHOP or FC chemotherapy
  • Liver enzymes \>3x normal or bilirubin \>2.5x normal (not due to lymphoma)
  • Creatinine \>2x normal value, corrected for age and weight (not due to lymphoma)
  • Patients with unresolved hepatitis B or C infection or known HIV positive infection
  • Uncontrolled infection
  • Patients with a serious depression that needed therapy within the last 5 years
  • +2 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (7)

General University Hospital, 1St Department of Medicine

Prague, CZ-12808, Czechia

Location

Nordic Lymphoma Group

Copenhagen, DK-2100, Denmark

Location

Groupe D´Etudes des Lymphomes De l´Adulte (GELA)

Paris, F-75743, France

Location

German Low Grade Study Group (Glsg)

Munich, D-81377, Germany

Location

Ospedale Ferratotto, Divisione Di Ematologia

Catania, I-95124, Italy

Location

HOVON - Dutch Haemato-Oncology Association (HOVON-Datacenter)

Rotterdam, NL-3008 AE, Netherlands

Location

The Maria Sklodowska Memorial, Cancer Center - Inst. of Oncology

Warsaw, PL-02-781, Poland

Location

Related Publications (5)

  • Kluin-Nelemans HC, Hoster E, Hermine O, Walewski J, Trneny M, Geisler CH, Stilgenbauer S, Thieblemont C, Vehling-Kaiser U, Doorduijn JK, Coiffier B, Forstpointner R, Tilly H, Kanz L, Feugier P, Szymczyk M, Hallek M, Kremers S, Lepeu G, Sanhes L, Zijlstra JM, Bouabdallah R, Lugtenburg PJ, Macro M, Pfreundschuh M, Prochazka V, Di Raimondo F, Ribrag V, Uppenkamp M, Andre M, Klapper W, Hiddemann W, Unterhalt M, Dreyling MH. Treatment of older patients with mantle-cell lymphoma. N Engl J Med. 2012 Aug 9;367(6):520-31. doi: 10.1056/NEJMoa1200920.

    PMID: 22873532RESULT

  • Hoster E, Delfau-Larue MH, Macintyre E, Jiang L, Stilgenbauer S, Vehling-Kaiser U, Salles G, Thieblemont C, Tilly H, Wirths S, Feugier P, Hubel K, Schmidt C, Ribrag V, Kluin-Nelemans JC, Dreyling M, Pott C; European MCL MRD Working Group and the European MCL Network. Predictive Value of Minimal Residual Disease for Efficacy of Rituximab Maintenance in Mantle Cell Lymphoma: Results From the European Mantle Cell Lymphoma Elderly Trial. J Clin Oncol. 2024 Feb 10;42(5):538-549. doi: 10.1200/JCO.23.00899. Epub 2023 Nov 22.

    PMID: 37992261DERIVED

  • Kluin-Nelemans HC, Hoster E, Hermine O, Walewski J, Geisler CH, Trneny M, Stilgenbauer S, Kaiser F, Doorduijn JK, Salles G, Szymczyk M, Tilly H, Kanz L, Schmidt C, Feugier P, Thieblemont C, Zijlstra JM, Ribrag V, Klapper W, Pott C, Unterhalt M, Dreyling MH. Treatment of Older Patients With Mantle Cell Lymphoma (MCL): Long-Term Follow-Up of the Randomized European MCL Elderly Trial. J Clin Oncol. 2020 Jan 20;38(3):248-256. doi: 10.1200/JCO.19.01294. Epub 2019 Dec 5.

    PMID: 31804876DERIVED

  • Hoster E, Klapper W, Hermine O, Kluin-Nelemans HC, Walewski J, van Hoof A, Trneny M, Geisler CH, Di Raimondo F, Szymczyk M, Stilgenbauer S, Thieblemont C, Hallek M, Forstpointner R, Pott C, Ribrag V, Doorduijn J, Hiddemann W, Dreyling MH, Unterhalt M. Confirmation of the mantle-cell lymphoma International Prognostic Index in randomized trials of the European Mantle-Cell Lymphoma Network. J Clin Oncol. 2014 May 1;32(13):1338-46. doi: 10.1200/JCO.2013.52.2466. Epub 2014 Mar 31.

    PMID: 24687837DERIVED

  • Pott C, Hoster E, Delfau-Larue MH, Beldjord K, Bottcher S, Asnafi V, Plonquet A, Siebert R, Callet-Bauchu E, Andersen N, van Dongen JJ, Klapper W, Berger F, Ribrag V, van Hoof AL, Trneny M, Walewski J, Dreger P, Unterhalt M, Hiddemann W, Kneba M, Kluin-Nelemans HC, Hermine O, Macintyre E, Dreyling M. Molecular remission is an independent predictor of clinical outcome in patients with mantle cell lymphoma after combined immunochemotherapy: a European MCL intergroup study. Blood. 2010 Apr 22;115(16):3215-23. doi: 10.1182/blood-2009-06-230250. Epub 2009 Dec 23.

    PMID: 20032498DERIVED

Related Links

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

RituximabCyclophosphamideDoxorubicinVincristinePrednisonefludarabineInterferon-alphaR-CHOP protocol

Condition Hierarchy (Ancestors)

Lymphoma, Non-HodgkinLymphomaNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-DerivedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsPhosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus CompoundsDaunorubicinAnthracyclinesNaphthacenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicPolycyclic CompoundsAminoglycosidesGlycosidesCarbohydratesVinca AlkaloidsSecologanin Tryptamine AlkaloidsIndole AlkaloidsAlkaloidsHeterocyclic CompoundsIndolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingIndolizidinesIndolizinesPregnadienediolsPregnadienesPregnanesSteroidsFused-Ring CompoundsInterferon Type IInterferonsCytokinesIntercellular Signaling Peptides and ProteinsPeptidesBiological Factors

Study Officials

  • Hanneke C. Kluin-Nelemans, PhD

    University Hospital Groningen, Dept. of Hematology

    PRINCIPAL INVESTIGATOR

  • Martin Dreyling, PhD

    University Hospital Grosshadern/LMU, Dept. of Medicine III

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor of Medicine

Study Record Dates

First Submitted

September 13, 2005

First Posted

September 21, 2005

Study Start

January 14, 2004

Primary Completion

December 1, 2018

Study Completion

December 1, 2018

Last Updated

March 7, 2017

Record last verified: 2017-03

Data Sharing

IPD Sharing
Will not share

Locations

IT(1)CZ(1)DE(1)DK(1)NL(1)PL(1)FR(1)