Title | An open-label, multi-center, three arm randomized, phase III study to compare the efficacy and safety of RO5072759 + chlorambucil (GClb), rituximab + chlorambucil (RClb) or chlorambucil (Clb) alone in previously untreated CLL patients with comorbidities |
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Protocol IDs | EUDRACT-2009-012476-28 NCT01010061 (06 Nov. 2009) BO21004 |
Participating Countries | Germany, Australia, Croatia, Romania, Czech Republic, Bulgaria, Slovakia, Canada, Switzerland, Estonia, Argentina, Thailand, New Zealand, Hong Kong, Italy, Spain, United Kingdom, Mexico, Russia, Austria, Netherlands, France, Denmark, Brazil, USA |
Status | completed |
Contact | DCLLSG Office: Tel. +49 (0) 221-478-88220 |
Design | Prospective, international, multicentre, open label, 3-arm randomized phase III study |
Primary Endpoint(s) | progression free survival (PFS) |
Secondary Endpoints | - Response rate (ORR/CR/PR), duration of response and disease-free survival in CR-patients, overall survival - Molecular remission: minimal residual disease (MRD) - Safety profile: AEs, laboratory parameters - Pharmacokinetics of RO5072759 (GA101) in combination with Clb - Quality of Life (EORTC questionnaire) |
Study Population | B-CLL according to NCI criteria Stage Binet C or stage Binet B / A requiring treatment according to the NCI criteria Relvant comorbidities (CIRS-score > 6 and/or creatinine clearance < 70 ml/min) No pretreatment Age ≥ 18 years |
Treatment | Maximum of 6 cycles, each with a duration of 28 days: |
Arm A (GClb) RO5072759 (GA101): 1000 mg i.v.; day 1, 8 and 15 (cycle 1), day 1 (cycle 2 - 6) + Chlorambucil: 0.5 mg/kg body weight p.o., day 1 and 15 |
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Arm B: (RClb) Rituximab: 375 mg/m² i.v., day 1, cycle 1 Rituximab: 500 mg/m² i.v., day 1, cycle 2-6 + Chlorambucil: 0.5 mg/kg body weight p.o., day 1 and 15 |
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Arm C (Clb) Chlorambucil: 0.5 mg/kg body weight p.o., day 1 and 15 |
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Patients recruited | 781 patients |
Time schedule | Recruitment period: 12 April 2010 - 04 July 2012 End of study: Aug 2017 Clinical Study Report / Publication: Feb 2018 End of archiving period: Aug 2032 |
Sponsor | Hoffmann-La Roche (exUS),
Genentech (USA) in collaboration with the German CLL study group (GCLLSG) |
Principal Investigator | Dr. Valentin Goede, Internal Medicine I, University Hospital 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] Herling CD, Klaumünzer M, Krings Rocha C, Altmüller J, Thiele H, Bahlo J, Kluth S, Crispatzu G, Herling M, Schiller J, Engelke A, Tausch E, Döhner H, Fischer K, Goede V, Nürnberg P, Reinhardt HC, Stilgenbauer S, Hallek M, Kreuzer KA Complex karyotypes, KRAS and POT1 mutations impact outcome in CLL after chlorambucil based chemo- or chemoimmunotherapy Blood. 2016 May 25 pii: blood-2016-01-691550. [Epub ahead of print] Goede V, Fischer K, Engelke A, Schlag R, Lepretre S, Montero LF, Montillo M, Fegan C, Asikanius E, Humphrey K, Fingerle-Rowson G, Hallek M Obinutuzumab as frontline treatment of chronic lymphocytic leukemia: Updated results of the CLL11 study Leukemia. 2015 Jul;29(7):1602-4 Goede V, Fischer K, Busch R, Engelke A, Eichhorst B, Wendtner CM, Chagorova T, de la Serna J, Dilhuydy MS, Illmer T, Opat S, Owen CJ, Samoylova O, Kreuzer KA, Stilgenbauer S, Döhner H, Langerak AW, Ritgen M, Kneba M, Asikanius E, Humphrey K, Wenger M, Hallek M Obinutuzumab plus Chlorambucil in Patients with CLL and Coexisting Conditions N Engl J Med. 2014 Mar 20;370(12):1101-10 Goede V, Fischer K, Busch R, Jaeger U, Dilhuydy MS, Wickham N, De Guibert S, Ritgen M, Langerak AW, Bieska G, Engelke A, Humphrey K, Wenger M, Hallek M Chemoimmunotherapy with GA101 plus chlorambucil in patients with chronic lymphocytic leukemia and comorbidity: results of the CLL11 (BO21004) safety run-in Leukemia. 2013 Apr;27(5):1172-4 |