Induction Chemotherapy (R-CHOP Vs. R-FC) Followed by Interferon Maintenance Versus Rituximab Maintenance in MCL (MCLelderly)

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1 1 von :27 Home Search Study Topics Glossary Study 1 of 24 for search of: MCL elderly Previous Study Return to Search Results Next Study Full Text View Tabular View No Study Results Posted Related Studies Induction Chemotherapy (R-CHOP Vs. R-FC) Followed by Interferon Maintenance Versus Rituximab Maintenance in MCL (MCLelderly) This study is currently recruiting participants. Verified January 2012 by European Mantle Cell Lymphoma Network First Received on September 13, Last Updated on January 3, 2012 History of Changes Sponsor: Collaborators: Information provided by (Responsible Party): ClinicalTrials.gov Identifier: European Mantle Cell Lymphoma Network German Low Grade Lymphoma Study Group Lymphoma Study Association HOVON - Dutch Haemato-Oncology Association Nordic Lymphoma Group Dr. M. Dreyling (co-chairman), European Mantle Cell Lym NCT Purpose 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? Condition Intervention Phase Lymphoma, Mantle-Cell Drug: Rituximab Drug: Cyclophosphamide Drug: Doxorubicin Drug: Vincristine Drug: Prednisone Drug: Fludarabine Drug: Interferon-alpha Drug: pegylated formula Interferon-alpha 2b Procedure: : R-CHOP Procedure: : R-FC Procedure: Interferon maintenance Procedure: Rituximab maintenance Phase 3 Study Type: Interventional

2 2 von :27 Study Design: Official Title: Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment Efficacy of Maintenance Therapy With Rituximab After Induction Chemotherapy (R-CHOP vs. R-FC) for Elderly Patients With Mantle Cell Lymphoma Not Suitable for Autologous Stem Cell Transplantation Resource links provided by NLM: MedlinePlus related topics: Lymphoma Drug Information available for: Cyclophosphamide Prednisone Vincristine sulfate Interferon Fludarabine Doxorubicin Doxorubicin hydrochloride Fludarabine phosphate Interferon alfa-2a Interferon alfa-2b Rituximab U.S. FDA Resources Further study details as provided by European Mantle Cell Lymphoma Network: Primary Outcome Measures: First randomisation: Reduction of lymphoma mass measured by the complete remission (CR) rate Second randomisation: progression-free survival after end of initial Secondary Outcome Measures: 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 Side-effects of maintenance therapy Estimated Enrollment: 570 Study Start Date: January 2004 Estimated Study Completion Date: January 2014 Estimated Primary Completion Date: January 2012 (Final data collection date for primary outcome measure) Arms Active Comparator: 1 1. randomisation: R-CHOP 2. randomisation: IFN maintenance Assigned Interventions Drug: Rituximab antibody Drug: Cyclophosphamide Drug: Doxorubicin Drug: Vincristine Drug: Prednisone coricosteroide Drug: Interferon-alpha cytokine Drug: pegylated formula Interferon-alpha 2b

3 3 von :27 cytokine Procedure: : R-CHOP immuno- Procedure: Interferon maintenance cytokine Experimental: randomisation: R-FC randomisation: Rituximab maintnenance Drug: Rituximab antibody Drug: Cyclophosphamide Drug: Fludarabine Procedure: : R-FC immuno- Procedure: Rituximab maintenance antibody Detailed Description: This study investigates two independent questions in the treatment of elderly patients with mantle cell lymphomas: To test in elderly patients with advanced mantle cell lymphoma, whether rituximab plus a combination of fludarabine with cyclophosphamide (6 FC cycles) results in a higher reduction of lymphoma mass measured by the percentage of CR than rituximab combined with the standard scheme (8 CHOP cycles). To compare maintenance therapy with rituximab with maintenance with interferon-alpha or pegylated interferon for progression free survival, after 2 different regimens of induction chemo-immunotherapy in elderly patients with mantle cell lymphoma. This study will be performed as a prospective, randomized, open-label multicenter phase III trial. All patients will be randomized for an initial cytoreductive therapy with R-FC or R-CHOP. The parameter for the comparison of R-FC and R-CHOP will be the percentage of complete remissions after initial cytoreductive therapy. According to the known results of R-FC and R-CHOP in lymphoma therapy, a relevant difference between R-CHOP and R-FC in the overall response rates is not expected. For both therapies an overall response rate of about 90% is expected. Since it is well known that the prognosis of patients who do not reach at least a PR in the initial therapy is very poor, it will be also necessary to control this parameter during the study. If an unexpected relevant difference in the overall response rates is observed during the study, the initial randomisation should be stopped and all patients should be assigned to the superior therapy. In this case the CR rates will not be important for the choice of the initial therapy. If no relevant differences in the overall response rates are observed, a one sided Fisher test will be performed at the end of the recruitment to test whether the rate of CR's after R-FC is significantly improved compared to R-CHOP. The statistical parameters for controlling the overall response rates and for testing the CR rates are chosen in the following way: The working significance level for all statistical evaluations in this part of the study will be set to alpha=0.05. The expected CR rate after R-CHOP is according to the observations about 50%; a clinical relevant improvement by R-FC would be a CR rate of 65%. Such an improvement should be detected by the one sided Fisher test with a power of about 95%. According to these parameters about 246 observations for each treatment would be necessary. To control the overall response rates, a difference of 85% to 95% will be clinically so relevant that initial randomisation should be terminated with a probability of about 95%. Overall response rates will be controlled by a restricted sequential procedure. Patients achieving at least a partial remission after R-FC or R-CHOP will be randomised for interferon maintenance versus rituximab maintenance in order to evaluate the impact of maintenance therapy in progression free survival. The improvement expected by the new maintenance with rituximab for progression free survival can be expressed by reduction of relative risk (rr). Since a risk reduction to 60% was observed for indolent lymphomas by interferon maintenance, this seems to be a clinical relevant improvement for the new maintenance therapy. For a working significance level alpha=0.05 and a power of 95% the number of events (relapse or death) necessary for a two sided fixed sample

4 4 von :27 trial is about 200. During this study the progression free survival in patients after successful initial therapy will be monitored by an equivalent restricted sequential procedure with a maximum number of 240 observation. In order to evaluate the impact of initial therapy and maintenance therapy on overall survival in this patients, a total follow up of about 15 years for this study is expected. Eligibility Ages Eligible for Study: Genders Eligible for Study: Accepts Healthy Volunteers: 60 Years and older Both No Criteria Inclusion Criteria: 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 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. Exclusion Criteria: 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 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 Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule Concomitant or previous malignancies other than basal cell or squamous cell skin cancer, in situ cervical cancer and other cancer for which the patient has been disease-free for at least 5 years Contacts and Locations

5 5 von :27 Please refer to this study by its ClinicalTrials.gov identifier: NCT Contacts Contact: Michael Unterhalt, Dr ext 4915 Michael.Unterhalt@med.uni-muenchen.de Contact: Martin Dreyling, PhD ext 2202 Martin.Dreyling@med.uni-muenchen.de Locations Czech Republic General University Hospital, 1St Department of Medicine Praha, Czech Republic, CZ Contact: Marek Trnény, MD trneny@cesnet.cz Principal Investigator: Marek Trnény, MD Denmark France Nordic Lymphoma Group Copenhagen, Denmark, DK-2100 Contact: Christian Geisler, MD geisler@rh.dk Principal Investigator: Christian Geisler, MD Groupe D Etudes des Lymphomes De l Adulte (GELA) Paris, France, F Contact: Guylène Chartier Guylene.chartier@chu-stlouis.fr Contact: Olivier Hermine, PhD hermine@necker.fr Principal Investigator: Olivier Hermine, PhD Germany German Low Grade Study Group (Glsg) Munich, Germany, D Contact: Michael Unterhalt, Dr ext 4915 Michael.Unterhalt@med.uni-muenchen.de Contact: Martin Dreyling, PhD ext 2202 Martin.Dreyling@med.uni-muenchen.de Principal Investigator: Martin Dreyling, PhD Italy Ospedale Ferratotto, Divisione Di Ematologia Catania, Italy, I Contact: Francesco Di Raimondo, PhD Principal Investigator: Francesco Di Raimondo, PhD Netherlands HOVON - Dutch Haemato-Oncology Association (HOVON-Datacenter) Rotterdam, Netherlands, NL-3008 AE Contact: Christel van Hooije Contact: Hanneke C. Kluin-Nelemans, PhD j.c.kluin.nelemans@int.azg.nl Principal Investigator: Hanneke C. Kluin-Nelemans, PhD Poland The Maria Sklodowska Memorial, Cancer Center - Inst. of Oncology Warszawa, Poland, PL Contact: Jan Walewski, MD walewski@coi.waw.pl Contact: Marek P Nowacki, MD Principal Investigator: Jan Walewski, MD Sponsors and Collaborators European Mantle Cell Lymphoma Network German Low Grade Lymphoma Study Group

6 6 von :27 Lymphoma Study Association HOVON - Dutch Haemato-Oncology Association Nordic Lymphoma Group Investigators Principal Investigator: Hanneke C. Kluin-Nelemans, PhD University Hospital Groningen, Dept. of Hematology Study Chair: Martin Dreyling, PhD University Hospital Grosshadern/LMU, Dept. of Medicine I More Information Additional Information: official webpage of the European MCLNetwork Publications: Dreyling M, Hoster E, Hermine O, Kluin-Nelemans JC, Walewski J, Trneny M, Geisler C, Unterhalt M, Hiddemann W. European MCL Network: An Update on Current First Line Trials. Blood 2007; 110 (Issue 11) # 388 Lenz G, Dreyling M, Schiegnitz E, Forstpointner R, Wandt H, Freund M, Hess G, Truemper L, Diehl V, Kropff M, Kneba M, Schmitz N, Metzner B, Pfirrmann M, Unterhalt M, Hiddemann W; German Low-Grade Lymphoma Study Group. Myeloablative radio followed by autologous stem cell transplantation in first remission prolongs progression-free survival in follicular lymphoma: results of a prospective, randomized trial of the German Low-Grade Lymphoma Study Group. Blood Nov 1;104(9): Epub 2004 Jul 6. Forstpointner R, Unterhalt M, Dreyling M, Bock HP, Repp R, Wandt H, Pott C, Seymour JF, Metzner B, Hanel A, Lehmann T, Hartmann F, Einsele H, Hiddemann W. Maintenance therapy with rituximab leads to a significant prolongation of response duration after salvage therapy with a combination of rituximab, fludarabine, cyclophosphamide and mitoxantrone (R-FCM) in patients with relapsed and refractory follicular and mantle cell lymphomas - results of a prospective randomized study of the German low grade lymphoma study group (GLSG). Blood Aug 31; [Epub ahead of print] Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number): Pott C, Hoster E, Delfau-Larue MH, Beldjord K, Böttcher 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 immuno: a European MCL intergroup study. Blood Apr 22;115(16): Epub 2009 Dec 23. Responsible Party: Dr. M. Dreyling (co-chairman), Professor of Medicine, European Mantle Cell Lymphoma Network ClinicalTrials.gov Identifier: NCT History of Changes Other Study ID Numbers: MCL Study First Received: September 13, 2005 Last Updated: January 3, 2012 Health Authority: Germany: Federal Institute for Drugs and Medical Devices Keywords provided by European Mantle Cell Lymphoma Network: Lymphoma, Mantle-Cell C Elderly patients C Chemotherapy C Maintenance therapy Additional relevant MeSH terms: Lymphoma Lymphoma, Mantle-Cell Neoplasms by Histologic Type Fludarabine monophosphate Rituximab Fludarabine

7 7 von :27 Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Lymphoma, Non-Hodgkin Interferon-alpha Interferon Alfa-2a Interferon Alfa-2b Interferons Cyclophosphamide Reaferon Doxorubicin Prednisone Vincristine Antiviral Agents Anti-Infective Agents Therapeutic Uses Pharmacologic Actions Immunologic Factors Physiological Effects of Drugs Angiogenesis Inhibitors Angiogenesis Modulating Agents Growth Substances ClinicalTrials.gov processed this record on July 29, 2012 Contact Help Desk Lister Hill National Center for Biomedical Communications, U.S. National Library of Medicine, U.S. National Institutes of Health, U.S. Department of Health & Human Services, USA.gov, Copyright, Privacy, Accessibility, Freedom of Information Act