DCLLSG

CLL11 Trial

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
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
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
Arm C (Clb)
Chlorambucil: 0.5 mg/kg body weight p.o., day 1 and 15
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