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| Title | Phase III trial of combined immunochemotherapy with Fludarabine,
Cyclophosphamide and Rituximab (FCR) versus chemotherapy with Fludarabine and
Cyclophosphamide (FC) alone in patients with previously untreated chronic lymphocytic leukaemia CLL-8 / ML17102 Protocol of the German CLL Study Group (GCLLSG) |
|---|---|
| Protocol IDs | EUDRACT-2004-004938-14 ISRCTN02757147 NCT00281918 |
| Participating Countries | Germany, France, Czech Republic, Israel, Australia, Belgium, Austria, Denmark, New Zealand, Spain, Italy |
| Status | completed |
| Contact | DCLLSG Office: Tel. +49 (0) 221-478-88220 |
| Design | Prospektive, open-label, multicentre, 2-arm, randomized phase III trial |
| Primary Endpoint(s) | Progression-free survival (PFS) |
| Secondary Endpoint(s) | Event-free survival (EFS), overall survival, disease-free survival, duration of remission, time to new CLL or death, rates of molecular, complete and partial remission, response rates and survival times in biological subgroups, rates of treatment-related adverse effects, pharmacoeconomic impact, quality of life |
| Study Population | B-CLL, Binet-Stage C or B with need for treatment No pretreatment Age ≥ 18 years |
| Treatment | Arm FCR immunochemotherapy: Rituximab (Cycle 1: 375 mg/m2, d0;Cycles 2-6: 500 mg/m2, d1) + Fludarabine (25 mg/m2/d, d1-3) + Cyclophosphamide (250 mg/m2/d, d1-3) q28d; max 6 cycles |
| Arm FC chemotherapy: Fludarabine (25 mg/m2/d, d1-3) + Cyclophosphamide (250 mg/m2/d, d1-3) q28d; max 6 cycles |
|
| Patients recruited | 817 patients (FCR: 408, FC: 409) |
| Time schedule | Recruitment period: 21 Jul. 2003 - 04 Apr. 2006
End of study: Oct 2011 Clinical Study Report / Publication: Jan 2013 End of archiving period: Oct 2026 |
| Sponsor | F. Hoffmann-La Roche Ltd |
| Principal investigator | Prof. Dr. M. Hallek, University of Cologne |
| Publications | Kurtz DM, Esfahani MS, Scherer F, Soo J, Jin MC, Liu CL, Newman AM, Dührsen U, Hüttmann A, Casasnovas O, Westin JR, Ritgen M, Böttcher S, Langerak AW, Roschewski M, Wilson WH, Gaidano G, Rossi D, Bahlo J, Hallek M, Tibshirani R, Diehn M, Alizadeh AA Dynamic Risk Profiling Using Serial Tumor Biomarkers for Personalized Outcome Prediction Cell. 2019 Jul 1. pii: S0092-8674(19)30639-7. doi: 10.1016/j.cell.2019.06.011. [Epub ahead of print] Jebaraj BMC, Tausch E, Landau DA, Bahlo J, Robrecht S, Taylor-Weiner AN, Bloehdorn J, Scheffold A, Mertens D, Böttcher S, Kneba M, Jäger U, Zenz T, Wenger MK, Fingerle-Rowson G, Wendtner C, Fink AM, Wu CJ, Eichhorst B, Fischer K, Hallek M, Döhner H, Stilgenbauer S Short telomeres are associated with inferior outcome, genomic complexity, and clonal evolution in chronic lymphocytic leukemia Leukemia. 2019 Mar 25. doi: 10.1038/s41375-019-0446-4. [Epub ahead of print] Dimier N, Delmar P, Ward C, Morariu-Zamfir R, Fingerle-Rowson G, Bahlo J, Fischer K, Eichhorst B, Goede V, van Dongen JJM, Ritgen M, Böttcher S, Langerak AW, Kneba M, Hallek M A model for predicting effect of treatment on progression-free survival using MRD as a surrogate endpoint in CLL Blood. 2018 Mar 1;131(9):955-962 Klymenko T, Bloehdorn J, Bahlo J, Robrecht S, Akylzhanova G, Cox K, Estenfelder S, Wang J, Edelmann J, Strefford JC, Wojdacz TK, Fischer K, Hallek M, Stilgenbauer S, Cragg M, Gribben J, Braun A Lamin B1 regulates somatic mutations and progression of B-cell malignancies Leukemia. 2017 Aug 14 [Epub ahead of print] Al-Sawaf O, Robrecht S, Bahlo J, Fink AM, Cramer P, von Tresckow J, Maurer C, Bergmann M, Seiler T, Lange E, Kneba M, Stilgenbauer S, Döhner H, Kiehl MG, Jäger U, Wendtner CM, Fischer K, Goede V, Hallek M, Eichhorst B, Hopfinger G Impact of gender on outcome after chemoimmunotherapy in patients with chronic lymphocytic leukaemia: A meta-analysis by the german CLL study group (GCLLSG) Leukemia. 2017 Jul 12 [Epub ahead of print] Kutsch N, Busch R, Bahlo J, Mayer J, Hensel M, Hopfinger G, Hess G, von Grünhagen U, Wendtner CM, Maria Fink A, Fischer K, Hallek M, Eichhorst B FCR front-line therapy and quality of life in patients with chronic lymphocytic leukemia Leuk Lymphoma. 2017 Feb;58(2):399-407 Edelmann J, Tausch E, Landau DA, Robrecht S, Bahlo J, Fischer K, Fink AM, Bloehdorn J, Holzmann K, Böttcher S, Werner L, Kneba M, Gribben JG, Neuberg DS, Wu CJ, Hallek M, Döhner H, Stilgenbauer S Frequent evolution of copy number alterations in CLL following first-line treatment with FC(R) is enriched with TP53 alterations: results from the CLL8 trial Leukemia. 2016 Dec 2 [Epub ahead of print] Kovacs G, Robrecht S, Fink AM, Bahlo J, Cramer P, von Tresckow J, Maurer C, Langerbeins P, Fingerle-Rowson G, Ritgen M, Kneba M, Döhner H, Stilgenbauer S, Klapper W, Wendtner CM, Fischer K, Hallek M, Eichhorst B, Böttcher S Minimal Residual Disease Assessment Improves Prediction of Outcome in Patients With Chronic Lymphocytic Leukemia (CLL) Who Achieve Partial Response: Comprehensive Analysis of Two Phase III Studies of the German CLL Study Group J Clin Oncol. 2016 Aug 29. pii: JCO671305. [Epub ahead of print] Müller D, Fischer K, Kaiser P, Eichhorst B, Walshe R, Reiser M, Kellermann L, Borsi L, Civello D, Mensch A, Bahlo J, Hallek M, Stock S, Fingerle-Rowson G Cost-effectiveness of rituximab in addition to fludarabine and cyclophosphamide (R-FC) for the first-line treatment of chronic lymphocytic leukemia Leuk Lymphoma. 2016 May;57(5):1130-9 Pflug N, Kluth S, Vehreschild JJ, Bahlo J, Tacke D, Biehl L, Eichhorst B, Fischer K, Cramer P, Fink AM, von Bergwelt-Baildon M, Stilgenbauer S, Hallek M, Cornely OA, Vehreschild MJ Efficacy of antineoplastic treatment is associated with the use of antibiotics that modulate intestinal microbiota Oncoimmunology. 2016 Apr 22;5(6):e1150399 Fischer K, Bahlo J, Fink AM, Goede V, Herling CD, Cramer P, Langerbeins P, von Tresckow J, Engelke A, Maurer C, Kovacs G, Herling M, Tausch E, Kreuzer KA, Eichhorst B, Böttcher S, Seymour JF, Ghia P, Marlton P, Kneba M, Wendtner CM, Döhner H, Stilgenbauer S, Hallek M Long term remissions after FCR chemoimmunotherapy in previously untreated patients with CLL: updated results of the CLL8 trial Blood. 2016 Jan 14;127(2):208-15 Landau DA, Tausch E, Taylor-Weiner AN, Stewart C, Reiter JG, Bahlo J, Kluth S, Bozic I, Lawrence M, Böttcher S, Carter SL, Cibulskis K, Mertens D, Sougnez CL, Rosenberg M, Hess JM, Edelmann J, Kless S, Kneba M, Ritgen M, Fink A, Fischer K, Gabriel S, Lander ES, Nowak MA, Döhner H, Hallek M, Neuberg D, Getz G, Stilgenbauer S, Wu CJ Mutations driving CLL and their evolution in progression and relapse Nature. 2015 Oct 22;526(7574):525-30 Weisser M, Yeh RF, Duchateau-Nguyen G, Palermo G, Nguyen TQ, Shi X, Stinson SY, Yu N, Dufour A, Robak T, Salogub GN, Dmoszynska A, Solal-Celigny P, Warzocha K, Loscertales J, Catalano J, Larratt L, Rossiev VA, Bence-Bruckler I, Geisler CH, Montillo M, Fischer K, Fink AM, Hallek M, Bloehdorn J, Busch R, Benner A, Döhner H, Valente N, Wenger MK, Stilgenbauer S, Dornan D PTK2 expression and immunochemotherapy outcome in chronic Blood. 2014 Jul 17;124(3):420-5 Pflug N, Bahlo J, Shanafelt TD, Eichhorst BF, Bergmann MA, Elter T, Bauer K, Malchau G, Rabe KG, Stilgenbauer S, Döhner H, Jäger U, Eckart MJ, Hopfinger G, Busch R, Fink AM, Wendtner CM, Fischer K, Kay NE, Hallek M Development of a comprehensive prognostic index for patients with chronic lymphocytic leukemia Blood. 2014 Jul 3;124(1):49-62 Stilgenbauer S, Schnaiter A, Paschka P, Zenz T, Rossi M, Döhner K, Bühler A, Böttcher S, Ritgen M, Kneba M, Winkler D, Tausch E, Hoth P, Edelmann J, Mertens D, Bullinger L, Bergmann M, Kless S, Mack S, Jäger U, Patten N, Wu L, Wenger MK, Fingerle-Rowson G, Lichter P, Cazzola M, Wendtner CM, Fink AM, Fischer K, Busch R, Hallek M, Döhner H Gene mutations and treatment outcome in chronic lymphocytic leukemia: results from the CLL8 trial Blood. 2014 May 22;123(21):3247-54 Cramer P, Bahlo J, Eichhorst B, Fischer K, Hallek M Extramedullary manifestations of chronic lymphocytic leukaemia are not unusual Leuk Res. 2013 Dec 1. pii: S0145-2126(13)00416-5 Cramer P, Fink AM, Busch R, Eichhorst B, Wendtner C, Pflug N, Langerbeins P, Bahlo J, Goede V, Schubert F, Döhner H, Stigenbauer S, Dreger P, Kneba M, Böttcher S, Mayer J, Hallek M, Fischer K Second-line Therapies of Patients initially treated with Fludarabine and Cyclophosphamide (FC) or Fludarabine, Cyclophosphamide and Rituximab (FCR) for Chronic Lymphocytic Leukemia (CLL) within the CLL8-Protocol of the German CLL Study Group (GCLLSG) Leuk Lymphoma. 2013 Aug;54(8):1821-2 Edelmann J, Holzmann K, Miller F, Winkler D, Bühler A, Zenz T, Bullinger L, Kühn MW, Gerhardinger A, Bloehdorn J, Radtke I, Su X, Ma J, Pounds S, Hallek M, Lichter P, Korbel J, Busch R, Mertens D, Downing JR, Stilgenbauer S, Döhner H High-resolution genomic profiling of chronic lymphocytic leukemia reveals new recurrent genomic alterations Blood. 2012 Oct 9. [Epub ahead of print] Böttcher S, Ritgen M, Fischer K, Stilgenbauer S, Busch RM, Fingerle-Rowson G, Fink AM, Bühler A, Zenz T, Wenger MK, Mendila M, Wendtner CM, Eichhorst BF, Döhner H, Hallek MJ, Kneba M. Minimal Residual Disease Quantification Is an Independent Predictor of Progression-Free and Overall Survival in Chronic Lymphocytic Leukemia: A Multivariate Analysis From the Randomized GCLLSG CLL8 Trial J Clin Oncol. 2012 Mar 20;30(9):980-8 Eichhorst BF, Fischer K, Fink AM, Elter T, Wendtner CM, Goede V, Bergmann M, Stilgenbauer S, Hopfinger G, Ritgen M, Bahlo J, Busch R, Hallek M Limited clinical relevance of imaging techniques in the follow-up of patients with advanced chronic lymphocytic leukemia: results of a meta-analysis Blood. 2011 Feb 10;117(6):1817-21 Hallek M, Fischer K, Fingerle-Rowson G, Fink AM, Busch R, Mayer J, Hensel M, Hopfinger G, Hess G, von Grünhagen U, Bergmann M, Catalano J, Zinzani PL, Caligaris-Cappio F, Seymour JF, Berrebi A, Jäger U, Cazin B, Trneny M, Westermann A, Wendtner CM, Eichhorst BF, Staib P, Bühler A, Winkler D, Zenz T, Böttcher S, Ritgen M, Mendila M, Kneba M, Döhner H, Stilgenbauer S; International Group of Investigators; German Chronic Lymphocytic Leukaemia Study Group. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial Lancet. 2010 Oct 2;376(9747):1164-74 Böttcher S, Stilgenbauer S, Busch R, Brüggemann M, Raff T, Pott C, Fischer K, Fingerle-Rowson G, Döhner H, Hallek M, Kneba M, Ritgen M. Standardized MRD flow and ASO IGH RQ-PCR for MRD quantification in CLL patientsafter rituximab-containing immunochemotherapy: a comparative analysis Leukemia. 2009 Nov;23(11):2007-17 |